Zwicker discovered that this chemical influx and efflux will exactly counterbalance each other when an active droplet reaches a certain volume, causing the droplet to stop growing.
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Artificial blood and spinal fluid flowed through the system, enabling molecules to be introduced to the influx BBB chip, which filtered into the brain chip, which in turn fed the efflux BBB chip.
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"It's hard for us to go tit for tat [on propaganda] with ISIS, which is very decentralized and is able to put up what they want," explained Michael McNerney, a former cybersecurity policy advisor for the secretary of Defense who now runs anti-hacking firm Efflux Systems.
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This active efflux mechanism is responsible for various types of resistance to bacterial pathogens within bacterial species - the most concerning being antibiotic resistance because microorganisms can have adapted efflux pumps to divert toxins out of the cytoplasm and into extracellular media. Efflux systems function via an energy-dependent mechanism (active transport) to pump out unwanted toxic substances through specific efflux pumps. Some efflux systems are drug-specific, whereas others may accommodate multiple drugs with small multidrug resistance (SMR) transporters. Efflux pumps are proteinaceous transporters localized in the cytoplasmic membrane of all kinds of cells.
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Thus, ontology terms for resistance profiles and mechanisms of actions were created for ARDB. Other things classified by ontology include drug target modification, drug enzymatic destruction and drug transport. Drug transporters are further subclassified by MFS Efflux pumps, SMR Efflux pumps, ABC Efflux pumps, RND Efflux pumps following conventions outlined in this paper. Currently, ARDB contains resistance information for 13,293 genes, 377 types, 257 antibiotics, 632 genomes, 933 species and 124 genera.
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Several trials are currently being conducted to develop drugs that can be co- administered with antibiotics to act as inhibitors for the efflux-mediated extrusion of antibiotics. As yet, no efflux inhibitor has been approved for therapeutic use, but some are being used to determine the prevalence of efflux pumps in clinical isolates and in cell biology research. Verapamil, for example, is used to block P-glycoprotein-mediated efflux of DNA-binding fluorophores, thereby facilitating fluorescent cell sorting for DNA content. Various natural products have been shown to inhibit bacterial efflux pumps including the carotenoids capsanthin and capsorubin, the flavonoids rotenone and chrysin, and the alkaloid lysergol.
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While glycylcyclines have greater efficacy against organisms with tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection, the glycylcyclines are not effective against organisms with chromosomal efflux pumps, such as Pseudomonas and Proteae.
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Some nanoparticles, for example zinc oxide, also inhibit bacterial efflux pumps.
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Thiomers are able to reversibly inhıbit efflux pumps. Because of this property the mucosal uptake of various efflux pump substrates such as anticancer drugs, antimycotic drugs and antiinflammatory drugs can be tremendously ımproved. The postulated mechanism of efflux pump inhibition is based on an interaction of thiolated polymers with the channel forming transmembrane domain of various efflux pumps such as P-gp and multidrug resistance proteins (MRPs). P-gp, for instance, exhibits 12 transmembrane regions forming a channel through which substrates are transported outside of the cell.
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Protein TolC, the outer membrane component of a tripartite efflux pump in Escherichia coli.AcrB, the other component of pump, Escherichia coli. All microorganisms, with a few exceptions, have highly conserved DNA sequences in their genome that are transcribed and translated to efflux pumps. Efflux pumps are capable of moving a variety of different toxic compounds out of cells, such as antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters via active efflux, which is vital part for xenobiotic metabolism.
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When N. gonorrhoeae encodes penA, the new PBP-2 that is synthesized is no longer recognized by the beta-lactams rendering the bacterium resistant. The mtr (multiple transferable resistance) gene encodes for an efflux pump.Rouquette-Loughlin, Dunham, Kuhn, Balthazar, Shafer (2003) The NorM Efflux Pump of Neisseria gonorrhoeae and Neissera meningitidis Recognizes Antimicrobial Cationic Compounds. Journal of Bacteriology 185:1101–1106 Efflux pumps mediate resistance to a variety of compounds including antibiotics, detergents, and dyes.
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Bacterial resistance towards tigecycline in Enterobacteriaceae (such as E. coli) is often caused by genetic mutations leading to an up-regulation of bacterial efflux pumps, such as the RND type efflux pump AcrAB. Some bacterial species such as Pseudomonas spp. can be naturally resistant to tigecycline through the constant over-expression of such efflux pumps. In some Enterobacteriaceae species, mutations in ribosomal genes such as rpsJ have been found to cause resistance to tigecycline.
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In support of this notion, RFC1 has been shown to catalyze efflux of thiamin pyrophosphate (TPP).
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Hrycyna works at Purdue University, which she joined as an Assistant Professor in 2000. Multidrug resistance cancer often arrises due to over expression of an energy-dependent multi-drug efflux pump, the multi-drug transporter P-glycoprotein. Whilst it is understood that P-glycoproteins are important in the movement of pharmalogical agents, their mechanism as a drug efflux pump is unclear. She looked at the mechanism of the efflux pump and how it functions in normal and cancerous cells.
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Drug resistance associated with drug efflux, mediated by P-glycoprotein, was originally reported in mammalian cells. In bacteria, Levy and colleagues presented the first evidence that antibiotic resistance was caused by active efflux of a drug. P-glycoprotein is the best- studied efflux pump and as such has offered important insights into the mechanism of bacterial pumps. Although some exporters transport a specific type of substrate, most transporters extrude a diverse class of drugs with varying structure.
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The response is initiated when sucrose is unloaded from the phloem into the apoplast. The increased sugar concentration in the apoplast decreases the water potential and triggers the efflux of potassium ions from the surrounding cells. This is followed by an efflux of water, resulting in a sudden change of turgor pressure in the cells of the pulvinus. Aquaporins on the vacuole membrane of pulvini allow for the efflux of water that contributes to the change in turgor pressure.
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From observations, it is known that chronic low-dose arsenic poisoning can lead to increased tolerance to its acute toxicity. MRP1-overexpressing lung tumor GLC4/Sb30 cells poorly accumulate arsenite and arsenate. This is mediated through MRP-1 dependent efflux. The efflux requires GSH, but no As-GSH complex formation.
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The pbuE gene encodes a purine base efflux pump. Binding of adenine to the pbuE adenine riboswitch disrupts the structure of a terminator stem that had been blocking access to the gene expression platform. In this way, an abundance of adenine can instigate the process of adenine's efflux from a cell.
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The second, AdeDE, is responsible for efflux of a wide range of substrates, including tetracycline, chloramphenicol, and various carbapenems.
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Furthermore, pegylated naloxegol becomes a substrate for the P-glycoprotein efflux transporter that transports the compound out of the CNS.
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Gram-negative bacteria harbor genes encoding for molecular pumps which can contribute to resistance of hydrophobic compounds like macrolides and lincosamides. Out of the many families of multidrug resistance pumps, lincosamides are most commonly shunted through pumps belonging to the resistance-nodulation-cell division superfamily. Staphylococci express efflux pumps with specificity for 14 and 15 member ring macrolides and streptogramin B, but not lincosamide molecules. Example of drug efflux through a pump belonging to the resistance-nodulation-cell division superfamily, the type of pump primarily responsible for lincosamide efflux.
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The concept is simple: the nanoparticles are too large to be effluxed by the MDR transporters, because the efflux function is strictly subjected to the size of its substrates, which is generally limited to a range of 300-2000 Da. Thereby the nanoparticulates remain insusceptible to the efflux, providing a means to accumulate in high concentrations.
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This mechanism falls under the first general resistance mechanism to beta-lactams. mtr encodes for the protein MtrD which is the efflux pump for N. gonorrhoeae. MtrD is among the Resistance Nodulation Division (RND) efflux pump superfamily. These pumps are proton antiporters where the antibiotic is pumped out of the cell while a proton is pumped into the cell.
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Some components of membranes play a key role in medicine, such as the efflux pumps that pump drugs out of a cell.
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Verapamil inhibits the ATP-binding cassette (ABC) transporter family of proteins found in stem cells and has been used to study cancer stem cells (CSC) within head and neck squamous cell carcinomas. Verapamil is also used in cell biology as an inhibitor of drug efflux pump proteins such as P-glycoprotein and other ABC transporter proteins. This is useful, as many tumor cell lines overexpress drug efflux pumps, limiting the effectiveness of cytotoxic drugs or fluorescent tags. It is also used in fluorescent cell sorting for DNA content, as it blocks efflux of a variety of DNA-binding fluorophores such as Hoechst 33342.
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Bacteria usually acquire resistance to tetracycline from horizontal transfer of a gene that either encodes an efflux pump or a ribosomal protection protein. Efflux pumps actively eject tetracycline from the cell, preventing the buildup of an inhibitory concentration of tetracycline in the cytoplasm. Ribosomal protection proteins interact with the ribosome and dislodge tetracycline from the ribosome, allowing for translation to continue.
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A.66.9) The Progressive Ankylosis (Ank) Family All functionally characterized members of the MOP superfamily catalyze efflux of their substrates, presumably by cation antiport.
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Aramchol activates cholesterol efflux by stimulating (2 to 4-fold) the ABCA1 transporter, a universal cholesterol export pump present in all cells. In animal models, this led to a significant reduction of blood and body cholesterol and an increase in fecal sterol output, mostly neutral sterols. Aramchol is the first small molecule that was shown to induce ABCA1-dependent cholesterol efflux without affecting transcriptional control.
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Atherosclerosis is marked by an excessive accumulation of cholesterol by macrophages, leading to their transformation into foam cells. This accumulation of cholesterol is caused by dysregulation of cholesterol influx and efflux. Since macrophages do not have the ability to limit the influx of cholesterol, the balance is completely dependent on efflux pathways. VLDLR is expressed by macrophages, and functions in the uptake of native lipoproteins.
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1) has 14 putative transmembrane regions, is induced only under anaerobic conditions, and is not repressed by glucose. DcuC may therefore function as a succinate efflux system during anaerobic glucose fermentation. However, when overexpressed, it can replace either DcuA or DcuB in catalysing fumarate-succinate exchange and fumarate uptake. DcuC shows the same transport modes as DcuA and DcuB (exchange, uptake, and presumably efflux of C4-dicarboxylates).
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Vesicle packing requires a large energy source to store large numbers of neurotransmitters into a small vesicular space at high concentrations. VMAT transport relies upon the pH and electrochemical gradient generated by a vesicular H+-ATPase for this energy source. The current model of VMAT function proposes that efflux of two protons against the H+ gradient is coupled with influx of one monoamine. The first H+ efflux generates a transporter conformation associated with a high-affinity amine-binding site in the cytosolic phase; the second H+ efflux is coupled with a second large conformational change that leads to amine transport from the cytosolic side into the vesicle, reducing amine-binding affinity.
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The TetA protein is an efflux pump. It has served as a model system for such proteins and has accumulated hundreds of publications indexed in PubMed.
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F.S. chronic fatigue syndrome. She has also worked to establish a link between autonomic dysfunction and muscle fatigue linking POTS with abnormal muscle PH and proton efflux.
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A sterol isolated from the species was reported as a rare example of a molecule capable of reversing multidrug efflux-mediated fungal resistance to the drug fluconazole.
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The ATPase assay is a membrane assay that indirectly measures the activity of efflux transporters. ATP Binding Cassette or efflux transporters mediate the transport of substrates across cell membranes against a concentration gradient. ATP cleavage is tightly linked to substrate translocation, as the energy for the substrate translocation is derived from ATP hydrolysis. ATP hydrolysis yields inorganic phosphate (Pi), which can be measured by a simple colorimetric reaction.
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The MATE family is made up of several members and includes a functionally characterized multidrug efflux system from Vibrio parahaemolyticus NorM (TC# 2.A.66.1.1), and several homologues from other closely related bacteria that function by a drug:Na+ antiport mechanism, a putative ethionine resistance protein of Saccharomyces cerevisiae (ERC1 (YHR032w); TC# 2.A.66.1.5), a cationic drug efflux pump in A. thaliana (i.e., AtDTX1 aka AT2G04040; TC# 2.A.66.1.
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Multiple mechanisms of streptogramin resistance have developed despite Synercid's fairly recent development. The three major mechanisms of resistance include active efflux, covalent target modification and antibiotic inactivation enzymes.
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There are also some multi-drug resistant (MDR) strains of P. aeruginosa that express β-lactamases as well as upregulated efflux pumps which can make treatment particularly difficult.
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Results in the studies indicated that JAK3-mediated phosphorylation of BCRP promotes its interactions with membrane-localized β-catenin essential not only for BCRP expression and surface localization, but also for the maintenance of BCRP-mediated intestinal drug efflux and barrier functions. It was observed that reduced intestinal JAK3 expression during human obesity or JAK3 knockout in mouse or siRNA- mediated β-catenin knockdown in human intestinal epithelial cells all result in significant loss of intestinal BCRP expression and compromised colonic drug efflux and barrier functions. These results uncover a mechanism of BCRP- mediated intestinal drug efflux and barrier functions and establish a role for BCRP in preventing CLGI-associated obesity both in humans and in mice. These studies have wider implications not only in our understanding of physiological and pathophysiological mechanisms of intestinal barrier functions and CLGI associated chronic inflammatory diseases but also in protein-mediated drug- efflux pharmacokinetic and pharmacodynamic characteristics of oral drug formulations.
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B. pseudomallei is intrinsically resistant to many antimicrobial agents by virtue of its efflux pump mechanism. This mediates resistance to aminoglycosides (AmrAB-OprA), tetracyclines, fluoroquinolones, and macrolides (BpeAB-OprB).
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The multidrug efflux transporter NorM from V. parahaemolyticus which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc.) and its homologue from E. coli were identified in 1998. NorM seems to function as drug/sodium antiporter which is the first example of Na+-coupled multidrug efflux transporter discovered. NorM is a prototype of a new transporter family and Brown et al. named it the multidrug and toxic compound extrusion family.
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The final variant was the S.O.1120 Ariel III which had a combined Turbomeca Arrius turbine-compressor rather than the two units of the earlier aircraft. With the space made from the power changes an extra seat was fitted. Another difference was the tail unit, the Ariel II had a single fin and rudder and used jet efflux from the turbine to provide directional control, a directional vane linked to the rudder directed the efflux.
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Upon high salt exposure, Arabidopsis experiences a negative osmotic pressure gradient between the salty solution and its xylem, and it absorbs Na+ through Na+ permeable transporters. The plant then reduces the impact of high Na+ abundance by improving Na+ efflux from its cells through SOS pathway Two different paths in the SOS pathway can activate SOS1, a molecule that causes sodium efflux. One path is the SOS2-SOS3, the other is the PLD path.
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The multidrug efflux transporter NorM from V. parahaemolyticus which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc.) and its homologue from E. coli were identified in 1998. NorM seems to function as drug/sodium antiporter which is the first example of Na+-coupled multidrug efflux transporter discovered. NorM is a prototype of a new transporter family and Brown et al. named it the multidrug and toxic compound extrusion family.
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Arsenite-antimonite transporters are membrane transporters that pump arsenite or antimonite out of a cell. Antimonite is the salt of antimony (Sb(III)) and has been found to significantly impact the toxicity of arsenite. The similar structure of As(III) and Sb(III) makes it plausible that certain transporters function in the efflux of both substrates. Arsenic efflux transporters exist in almost every organism and serve to remove this toxic compound from the cell.
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Opening of the BK channel leads to an increased K+-efflux which hyperpolarizes the resting membrane potential, reducing the excitability of the cell in which the BK-channel is expressed.
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Amino acid concentration in lymph node cells, for example, is kept at steady state with active transport as the primary source of entry, and diffusion as the source of efflux.
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This protein is believed to catalyze Co2+ and Ni2+ efflux. The overall reaction catalyzed by proteins of the NicO family is probably: [Ni2+ or Co2+] (in) → [Ni2+ or Co2+] (out).
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The release of the posterior closure, which can be velar or uvular, is the click efflux. Clicks are used in several African language families, such as the Khoisan and Bantu languages.
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The release of the posterior closure, which can be velar or uvular, is the click efflux. Clicks are used in several African language families, such as the Khoisan and Bantu languages.
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The selectivities of these channels may be relatively weak in comparison to voltage-gated channels. In addition, some MscS channels may function in amino acid efflux, Ca2+ regulation and cell division.
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Other defense mechanisms have also been noted in A. thaliana to thaxtomin A, including the initiation of programmed cell death, an efflux of hydrogen ions and an influx of calcium ions.
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Decreased P-gp expression has been found in Alzheimer's disease brains. Altered P-gp function has also been linked to inflammatory bowel diseases (IBD); however, due to its ambivalent effects in intestinal inflammation many questions remain so far unanswered. While decreased efflux activity may promote disease susceptibility and drug toxicity, increased efflux activity may confer resistance to therapeutic drugs in IBD. Mice deficient in MDR1A develop chronic intestinal inflammation spontaneously, which appears to resemble human ulcerative colitis.
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Therefore, we know that ABCA1 plays an important role in preventing cholesterol accumulation in macrophages. By enhancing miR-33 function, the level of ABCA1 is decreased, leading to decrease cellular cholesterol efflux to apoA-1. On the other hand, by inhibiting miR-33 function, the level of ABCA1 is increased and increases the cholesterol efflux to apoA-1. Suppression of miR-33 will lead to less cellular cholesterol and higher plasma HDL level through the regulation of ABCA1 expression.
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Tolerance to boron toxicity in cereals is known to be associated with reduced tissue accumulation of boron. Expression of genes from roots of boron-tolerant wheat and barley with high similarity to efflux transporters from Arabidopsis and rice lowered boron concentrations due to an efflux mechanism. The mechanism of energy coupling is not known, nor is it known if borate or boric acid is the substrate. Several possibilities (uniport, anion:anion exchange and anion:cation exchange) can account for the data.
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Streptogramin resistance is mediated through enzymatic drug inactivation, efflux or active transport of drug out of the cell, and most commonly, conformational alterations in ribosomal target binding sites. Enzymatic drug inactivation may occur in staphylococcal and enterococcal species through production of dalfopristin- inactivating acetyltransferase or quinupristin-inactivating hydrolase. Efflux or active transport of the drug may occur in coagulase-negative staphylococci and Enterococcus faecium. Constitutive ribosome modification has been seen in staphylococci with resistance seen in quinupristin only.
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Members of the ABCA subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesterol efflux pump in the cellular lipid removal pathway. While the complete 3D-structure of ABCA1 remains relatively unknown, there has been some determination of the c-terminus. The ABCA1 c-terminus contains a PDZ domain, responsible for mediating protein-protein interactions, as well as a VFVNFA motif essential for lipid efflux activity.
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Mutation and overexpression of SWEET9 in Arabidopsis led to corresponding loss of and increase in nectar secretion, respectively. After showing that SWEET9 is involved in nectar secretion, the next step was to determine at which phase of the process SWEET9 has its function. The 3 options were: phloem unloading, or uptake or efflux from nectary parenchyma. A combination of localization studies and starch accumulation assays showed that SWEET9 is involved in sucrose efflux from the nectary parenchyma.
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Ion release from guard cells causes stomatal pore closing: Other ion channels have been identified that mediate release of ions from guard cells, which results in osmotic water efflux from guard cells due to osmosis, shrinking of the guard cells, and closing of stomatal pores (Figures 1 and 2). Specialized potassium efflux channels participate in mediating release of potassium from guard cells.Schroeder JI (1988) K+ transport properties of K+ channels in the plasma membrane of Vicia faba guard cells.
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Due to the spatial, temporal, and numerical disproportions between Na+ influx and K+ efflux, the PNN provides a possible buffering system for extracellular cations. However, this hypothesis has yet to be proven.
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123: 833–843.Moshelion, M. and Moran, N. (2000) Potassium-efflux channels in extensor and flexor cells of the motor organ of Samanea saman are not identical. Effects of cytosolic calcium. Plant Physiol.
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The presence of these molecules causes a production of ROS and K+ efflux. NLRP1 recognizes lethal toxin from Bacillus anthracis and muramyl dipeptide. IPAF senses flagellin from Salmonella typhimurium, Pseudomonas aeruginosa, Listeria monocytogenes.
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In order for this activation to occur, auxin influx and efflux activity must be regulated within the plant cell. Lateral root developmental strategies indicated adaptations of the root system to different environmental niches.
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There is no evidence for DMF interaction with cytochrome P450 and the most common efflux and uptake transporters, and therefore no interactions are expected with medicinal products metabolised or transported by these systems.
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Large number cup sizes are used when viscosity is high, while low number cup sizes are used when viscosity is low. To determine the viscosity of a liquid, the cup is dipped and completely filled with the substance. After lifting the cup out of the substance the user measures the time until the liquid streaming out of it breaks up, this is the corresponding "efflux time". On paint standard specifications, one denotes viscosity in this manner: efflux time, Zahn cup number.
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The multidrug efflux transporter NorM from V. parahaemolyticus which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc.) and its homologue from E. coli were identified in 1998, which is the first of Solute carrier family 47 member. NorM seems to function as drug/sodium antiporter which is the first example of Na+-coupled multidrug efflux transporter. NorM is a prototype of a new transporter family and Brown et al. named it the multidrug and toxic compound extrusion family.
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Phosphorylation by either protein kinase can result in DAT internalization ( reuptake inhibition), but phosphorylation alone induces the reversal of dopamine transport through DAT (i.e., dopamine efflux). Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through an unidentified Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent pathway, in turn producing dopamine efflux. Through direct activation of G protein-coupled inwardly-rectifying potassium channels, reduces the firing rate of dopamine neurons, preventing a hyper-dopaminergic state.
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The PM-localized PIN proteins physically interact with a few members of the large PGP family of transporters that also work as auxin efflux carriers (PGP1 and PGP19 in Arabidopsis). These interactions result in a synergistic increase in auxin efflux. The activity and localization of the PM-localized PIN proteins is regulated by several phosphorylations on their large cytosolic hydrophilic loop carried out by kinases of the AGC family (e.g. PID, WAG1, WAG2, PID2 in Arabidopsis) and the D6PK kinase.
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Since efflux of water, minerals, and water-bound organisms leaving each watershed (and leaving the entire forest as well) can be monitored, the effects of changes experimentally introduced into the system can be measured.
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The asymmetrical localisation of PIN efflux carrier protein at the plasma membrane has been shown to involve the localized targeting of vesicles and the local regulation of endocytosis. The latter involves the actin cytoskeleton.
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This explains the incapability of the latter group to significantly contribute to the metal efflux required for survival in high copper environments. Structural and mechanistic details of copper-transporting P-type ATPase functionhave been described.
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Quinolones are a class of synthetic antibiotics that inhibit DNA replication, recombination, and repair by interacting with the bacterial DNA gyrase and/or topoisomerase IV. Second generation quinolones like ciprofloxacin and ofloxacin have been widely used to treat N. gonorrhoeae infections. Resistance to these antibiotics has developed over the years with chromosomal resistance being the primary mechanism. Low-level quinolone resistance has been linked to changes in cell permeability and efflux pumps. The NorM efflux pump is encoded by the norM gene and provides resistance to fluoroquinolones.
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At least one member (YebN of E. coli, TC# 2.A.107.1.1) has been shown to function as a putative manganese efflux pump. Manganese sensitivity and intracellular manganese levels significantly increased in bacteria when the mntP (formerly yebN) gene, which encodes the MntP efflux pump, was deleted. While manganese is a highly important trace nutrient for organisms from bacteria to humans, acting as an important element in the defense against oxidative stress and as an enzyme cofactor, it becomes toxic when present in excess.
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The mechanism of action of omadacycline is similar to that of other tetracyclines – inhibition of bacterial protein synthesis. Omadacycline has activity against bacterial strains expressing the two main forms of tetracycline resistance (efflux and ribosomal protection).
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The solute carriers and atypical SLCs are secondary active or facilitative transporters in humans. Collectively membrane transporters and channels are transportome. Transportomes govern cellular influx and efflux of not only ions and nutrients but drugs as well.
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The specific part of ATP synthase affected by bedaquiline is subunit c which is encoded by the gene atpE. Mutations in atpE can lead to resistance. Mutations in drug efflux pumps have also been linked to resistance.
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In eukaryotic cells, the existence of efflux pumps has been known since the discovery of P-glycoprotein in 1976 by Juliano and Ling. Efflux pumps are one of the major causes of anticancer drug resistance in eukaryotic cells. They include monocarboxylate transporters (MCTs), multiple drug resistance proteins (MDRs)- also referred as P-glycoprotein, multidrug resistance-associated proteins (MRPs), peptide transporters (PEPTs), and Na+ phosphate transporters (NPTs). These transporters are distributed along particular portions of the renal proximal tubule, intestine, liver, blood–brain barrier, and other portions of the brain.
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Efflux pumps are protein machines that use energy to pump antibiotics and other small molecules that get into the bacterial cytoplasm and the periplasmic space out of the cell. By constantly pumping antibiotics out of the cell, bacteria can increase the concentration of a given antibiotic required to kill them or inhibit their growth when the target of the antibiotic is inside the bacterium. A. baumannii is known to have two major efflux pumps which decrease its susceptibility to antimicrobials. The first, AdeB, has been shown to be responsible for aminoglycoside resistance.
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In addition to screening natural products for direct antibacterial activity, they are sometimes screened for the ability to suppress antibiotic resistance and antibiotic tolerance. For example, some secondary metabolites inhibit drug efflux pumps, thereby increasing the concentration of antibiotic able to reach its cellular target and decreasing bacterial resistance to the antibiotic. Natural products known to inhibit bacterial efflux pumps include the alkaloid lysergol, the carotenoids capsanthin and capsorubin, and the flavonoids rotenone and chrysin. Other natural products, this time primary metabolites rather than secondary metabolites, have been shown to eradicate antibiotic tolerance.
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Endothelial prostacyclin binds to prostanoid receptors on the surface of resting platelets. This event stimulates the coupled Gs protein to increase adenylate cyclase activity and increases the production of cAMP, further promoting the efflux of calcium and reducing intracellular calcium availability for platelet activation. ADP on the other hand binds to purinergic receptors on the platelet surface. Since the thrombocytic purinergic receptor P2Y12 is coupled to Gi proteins, ADP reduces platelet adenylate cyclase activity and cAMP production, leading to accumulation of calcium inside the platelet by inactivating the cAMP calcium efflux pump.
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Co-localized TAAR1 is an important regulator of the dopamine transporter that, when activated, phosphorylates DAT through protein kinase A (PKA) and protein kinase C (PKC) signaling. Phosphorylation by either protein kinase can result in DAT internalization ( reuptake inhibition), but phosphorylation alone induces reverse transporter function (dopamine efflux). Dopamine autoreceptors also regulate DAT by directly opposing the effect of TAAR1 activation. The human dopamine transporter (hDAT) contains a high affinity extracellular zinc binding site which, upon zinc binding, inhibits dopamine reuptake and amplifies amphetamine-induced dopamine efflux in vitro.
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Cif was first discovered by co- culturing P. aeruginosa with human airway epithelial cells and monitoring the resulting effect on chloride ion efflux across a polarized monolayer. After co-culture, the CFTR specific chloride ion efflux was found to be drastically reduced. This was determined to be caused by reduced levels of CFTR at the apical surface of these cells. This effect was later found to be the result of a single secreted protein produced by P. aeruginosa, which was named the CFTR inhibitory factor for this initial phenotype.
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Hypoxia provokes potassium efflux from cardiac muscles cells via the activation of ATP-sensitive potassium channels (KATP).Wilde, A. A. M. (1993). Role of ATP-sensitive K+ channel current in ischemic arrhythmias. Cardiovasc Drugs Ther 7, 521−526.
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Multidrug resistance is the most important limitation in anticancer therapy. It can develop in many chemically distinct compounds. Until now, several mechanisms are known to develop the resistance. The most common is production of so-called "efflux pumps".
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Apolipoprotein O is the first chondroitine sulphate chain containing apolipoprotein. Apolipoproteins are proteins that binds to lipids. Members of this family promote cholesterol efflux from macrophage cells. They are present in various lipoprotein complexes, including HDL, LDL and VLDL.
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A mutation of the SLC30A10 gene, a manganese efflux transporter necessary for decreasing intracellular Mn, has been linked with the development of this Parkinsonism-like disease. The Lewy bodies typical to PD are not seen in Mn-induced parkinsonism.
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Bicalutamide, as well as enzalutamide, have been found to act as inhibitors of P-glycoprotein efflux and ATPase activity. This action may reverse docetaxel resistance in prostate cancer cells by reducing transport of the drug out of these cells.
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Sodium–hydrogen antiporters, such as NHEDC2, convert the proton motive force established by the respiratory chain or the F1F0 mitochondrial ATPase into sodium gradients that drive other energy-requiring processes, transduce environmental signals into cell responses, or function in drug efflux.
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In their experiment, microdialysis was used to monitor dopamine efflux from the nucleus accumbens during three stages of sexual behaviour, these included: copulation, sexual satiety, and the reinitiation of sexual behaviour. Behavioural testing for the Coolidge effect consisted of several phases including, copulation with a female, reintroduction to the same female, access to the same female, introduction to a novel female, and copulation with the novel female. During these phases, dopamine and its metabolites were monitored. Results from this study found that overall there was a significant increase in dopamine efflux in response to both the first female and the second female.
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The NPC1L1 protein which sits on the luminal side of the enterocyte is responsible for sterol absorption. Its counterpart, the ABCG5/G8 ATP Binding Cassette protein which also sits on the luminal side of the enterocyte, and on the bile canaliculi side of the hepatocyte, is responsible for sterol efflux. Variations in each of these proteins causes variation in absorption and efflux of dietary and biliary sterols - both cholesterol and plant sterols. Although studies in humans have shown that consumption of phytosterols may reduce LDL levels, evidence to recommend them as a treatment for hypercholesterolemia is insufficient.
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Some investigations in cell lines have shown that imatinib resistance may be partly due to an increase in the expression of the P-glycoprotein efflux pump. By utilizing agents that inhibit P-glycoprotein activity imatinib susceptibility has been restored in some cases.
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Stenness parish adjoins the southern extremity of the Loch of Stenness, and also some notable standing stones. It is bounded on the west by the efflux of the loch, and a branch of Hoy Sound, and has been politically merged with Firth.
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HMR 1883 is a cardioselective ATP- sensitive potassium channel antagonist that prevents the potassium efflux, hence corrects the non-uniform refractory period in the ischemic tissue. A uniform refractory period corrects the conductance problems in the heart and prevents the re-entry arrhythmias.
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ArsB proteins are therefore members of a superfamily (called the IT (ion transporter) superfamily). However, ArsB has uniquely gained the ability to function in conjunction with ArsA in order to couple ATP hydrolysis to anion efflux. ArsAB belongs to the ArsA ATPase Superfamily.
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The 14a-demethylase (CYP51A1) gene is overexpressed in V. inaequalis strains resistant to myclobutanil. Phytopathology 91:102–110. Resistance to fungicides can also be developed by efficient efflux of the fungicide out of the cell. Septoria tritici has developed multiple drug resistance using this mechanism.
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One model suggests that APP acts to stabilize the iron efflux protein ferroportin in the plasma membrane of cells thereby increasing the total number of ferroportin molecules at the membrane. These iron- transporters can then be activated by known mammalian ferroxidases (i.e. ceruloplasmin or hephaestin).
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Sirolimus is metabolized by the CYP3A4 enzyme and is a substrate of the P-glycoprotein (P-gp) efflux pump; hence, inhibitors of either protein may increase sirolimus concentrations in blood plasma, whereas inducers of CYP3A4 and P-gp may decrease sirolimus concentrations in blood plasma.
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Mutations in the coding region of CYP51 genes, overexpression of CYP51, and overexpression of membrane efflux transporters can all lead to resistance to these antifungals. Consequently, the focus of azole research is beginning to shift towards identifying new ways to circumvent this major obstacle.
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Glycylcyclines are a class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection. Presently, tigecycline is the only glycylcycline approved for antibiotic use.
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The TerC family (Pfam 03741) includes the E. coli TerC protein (TC# 2.A.109.1.1) which has been implicated in tellurium resistance. It is hypothesized to catalyze efflux of tellurium ions. TerC is encoded by plasmid pTE53 from a clinical isolate of E. coli.
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Quinolone resistance genes are frequently located on the same plasmid as the ESBL genes. Examples of resistance mechanisms include different Qnr proteins, aminoglycose acetyltransferase aac(6')-Ib-cr that is able to hydrolyze ciprofloxacin and norfloxacin, as well as efflux transporters OqxAB and QepA.
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Acinetobacter baumannii is most common in hospitals, which has allowed for the development of resistance to all known antimicrobials. The Gram-negative short-rod-shaped (coccobacillus) A. baumannii thrives in a number of unaccommodating environments due to its tolerance to a variety of temperatures, pHs, nutrient levels, as well as dry environments. The Gram-negative aspects of the membrane surface of A. baumannii, including the efflux pump and outer membrane, affords it a wider range of antibiotic resistance. Additionally, some problematic A. baumannii strains are able to acquire families of efflux pumps from other species, and commonly first to develop new β-lactamases to improve β-lactam resistance.
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ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub- family ABCA), also known as the cholesterol efflux regulatory protein (CERP) is a protein which in humans is encoded by the ABCA1 gene. This transporter is a major regulator of cellular cholesterol and phospholipid homeostasis.
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7, 1984 and later with 3H-paroxetine,Stereoselectivity in the metabolism of 3H-noradrenaline during uptake into and efflux from the isolated rat vas deferens K.-H. Graefe, F. J. E. Stefano, S. Z. Langer: Naunyn-schmiedebergs Archives of Pharmacology - NAUNYN-SCHMIED ARCH PHARMACOL vol. 299, no.
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Ejaculatory duct obstruction (EDO) is a pathological condition which is characterized by the obstruction of one or both ejaculatory ducts. Thus, the efflux of (most constituents of) semen is not possible. It can be congenital or acquired. It is a cause of male infertility and/or pelvic pain.
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Puromycin resistance in yeast can also be conferred through expression of the puromycin N-acetyl-transferase (pac) gene. Lethal concentrations of puromycin are much higher for strains of Saccharomyces cerevisiae than mammalian cell lines. Deletion of the gene encoding the multidrug efflux pump Pdr5 sensitizes cells to puromycin.
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Third, Mg2+ efflux was observed via Mrs2p upon the artificial depolarisation of the mitochondrial membrane by valinomycin. Finally, the Mg2+ fluxes through Mrs2p are inhibited by cobalt (III) hexaammine. The kinetics of Mg2+ uptake by Mrs2p were determined in the Froschauer et al. (2004) paper on CorA in bacteria.
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The phylogenetic tree shows clustering according to function and organismal phylogeny. The putative formate efflux transporters (FocA; TC#s 1.A.16.1.1 and 1.A.16.1.3) of bacteria associated with pyruvate-formate lyase (pfl) comprise cluster I; the putative formate uptake permeases (FdhC; TC#s 1.A.16.2.
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The conduction velocity of a typical 0.5 mm squid axon is about 25 m/s. During a typical action potential in the cuttlefish Sepia giant axon, an influx of 3.7 pmol/cm2 (picomoles per centimeter2) of sodium is offset by a subsequent efflux of 4.3 pmol/cm2 of potassium.
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While the PGP auxin efflux carriers are evenly distributed, the PIN proteins normally maintain polar (i.e. asymmetric) localisation on the plasma membrane. That is to say they are most concentrated on one side of the cell. Furthermore, the asymmetrical localisation of the PIN proteins is coordinated between neighbouring cells.
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The cytoplasmic Cu+ chaperone CopZ transfers the metal directly to the TM-MBSs; however, loading both of the TM-MBSs requires binding of nucleotides to the enzyme. In agreement with the classical transport mechanism of P-type ATPases, occupancy of both transmembrane sites by cytoplasmic Cu+ is a requirement for enzyme phosphorylation and subsequent transport into the periplasmic or extracellular milieu. Transport studies have shown that most Cu+-ATPases drive cytoplasmic Cu+ efflux, albeit with quite different transport rates in tune with their various physiological roles. Archetypical Cu+-efflux pumps responsible for Cu+ tolerance, like the Escherichia coli CopA, have turnover rates ten times higher than those involved in cuproprotein assembly (or alternative functions).
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SR-BI has also been identified in the livers of non- mammalian species (turtle, goldfish, shark, chicken, frog, and skate), suggesting it emerged early in vertebrate evolutionary history. The turtle also seems to upregulate SR-BI during egg development, indicating that cholesterol efflux may be at peak levels during developmental stages.
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P-gp efflux activity is capable of lowering intracellular concentrations of otherwise beneficial compounds, such as chemotherapeutics and other medications, to sub- therapeutic levels. Consequently, P-gp overexpression is one of the main mechanisms behind decreased intracellular drug accumulation and development of multidrug resistance in human multidrug-resistant (MDR) cancers.
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In ovarian cancer, the ATP7B gene encodes for a copper efflux transporter, found to be upregulated in cisplatin-resistant cell lines and tumors. Development of antisense deoxynucleotides against ATP7B mRNA and treatment of an ovarian cancer cell line shows that inhibition of ATP7B increases sensitivity of the cells to cisplatin.
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23(9): p. 1500-8 It was later recognized that the cerebrospinal venous system represents a main route for efflux of venous blood from the brain. Modern imaging methodology, including MR scanning, have detailed the anastomoses of the cerebral and spinal venous systems in the suboccipital region.Takahashi, S., et al.
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The hormone that is found in multiple steps of lateral root development is called auxin. Auxin appears in the initiation, emergence and elongation of the roots. Auxin signals regulate the direction auxin efflux and auxin flow throughout the cell. This regulation is what directs and aids in lateral root development.
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Protein Kinase A is directed to specific sub cellular locations after tethering to Protein kinase A anchoring proteins (AKAPs). Sarcoplasmic Reticulum Ca2+ release channel or Ryanodine receptor (Ryr) co-localizes with the muscle AKAP. RyR phosphorylation and efflux of Ca 2+ is increased by localisation of PKA at RyR by mAKP.
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Similar to dopamine, amphetamine dose-dependently increases the level of synaptic norepinephrine, the direct precursor of epinephrine. Based upon neuronal expression, amphetamine is thought to affect norepinephrine analogously to dopamine. In other words, amphetamine induces TAAR1-mediated efflux and reuptake inhibition at phosphorylated , competitive NET reuptake inhibition, and norepinephrine release from .
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M-channels are the reason for slow depolarizations produced by ACh and LHRH in the autonomic ganglia and other specified areas. 1\. Initial depolarization of a neuron increases likelihood that M-channels will open. 2\. M-channels generate an outward potassium current (IK). 3\. Potassium efflux counteracts sodium influx in action potential (AP).
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Prokaryotic ABC exporters are abundant and have close homologues in eukaryotes. This class of transporters is studied based on the type of substrate that is transported. One class is involved in the protein (e.g. toxins, hydrolytic enzymes, S-layer proteins, lantibiotics, bacteriocins, and competence factors) export and the other in drug efflux.
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There is further evidence that inhibiting BK channels would prevent the efflux of potassium and thus reduce the usage of ATP, in effect allowing for neuronal survival in low oxygen environments. BK channels can also function as a neuronal protectant in terms such as limiting calcium entry into the cells through methionine oxidation.
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Bacterial small RNAs are noncoding RNAs that regulate various cellular processes. Three sRNAs, AbsR11, AbsR25, and AbsR28, have been experimentally validated in the MTCC 1425 (ATCC15308) strain, which is a (multidrug- resistant) strain showing resistance to 12 antibiotics. AbsR25 sRNA could play a role in the efflux pump regulation and drug resistance.
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Pho1 of A. thaliana is a member of the PHO1 family (11 paralogues in A. thaliana). This protein is 782 amino acyl residues in length and possesses 7 transmembrane segments (TMSs). It functions in inorganic phosphate transport and homeostasis. Pho1 catalyzes efflux of phosphate from epidermal and cortical cells into the xylem.
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Phospholipase D2 (PLD2) binds PIP2 and localizes with lipid rafts. Increases in cholesterol overcome PIP2 binding and sequester PLD2 into GM1 lipid rafts away from its substrate phosphatidylcholine. Efflux of cholesterol causes PLD2 to translocate to PIP2 domains where it is activated by substrate presentation. Both PIP2 signaling and cholesterol signaling regulate the enzyme.
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Auxin relies on PIN1 which works as an auxin efflux carrier. PIN1 positioning upon membranes determines the directional flow of the hormone from higher to lower concentrations. Initiation of primordia in apical meristems is correlated to heightened auxin levels. Genes required to specify the identity of cells arrange and express based on levels of auxin.
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High salinity increases the activity of the enzyme PLD1, which causes the accumulation of phosphatidic acid. PA activates MPK6, a protein kinase regulating translation efficiency in high salinity conditions. Then MPK6 phosphorylates SOS1 and again causes sodium efflux. One of the experiments providing the previous pathway utilized Arabidopsis seedlings grown inside X-gal dishes.
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One is TPK3, a potassium channel that is activated by Ca2+ and conducts K+ from the thylakoid lumen to the stroma which helps establish the pH gradient. On the other hand, the electro-neutral K+ efflux antiporter (KEA3) transports K+ into the thylakoid lumen and H+ into the stroma which helps establish the electric field.
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The rudder projected beneath the boom into the jet efflux and provided effective yaw control even when the aircraft was stationary. The undercarriage was a simple pair of tubular steel skids directly attached to the box structure, porter bars could be attached to the skids to allow the rotorcraft to be carried by hand.
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Pi3 blocks the Kv1.3 channels in the human T lymphocytes with a Kd of 500 pM. The block is reversible and not voltage- dependent. Recovery of the channels from inactivation is not affected by Pi3. In addition it has been shown by 86Rb efflux assay of synaptosomes that Pi3 blocks voltage-gated, rapidly inactivating channels.
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Another project attempted noise control of jet engines by modification of the efflux nozzle to improve mixing with external flow. He was awarded a patent and collected some royalties. Daughter Judith arrived in 1949, and the following year Alec became Professor at Cranfield. In 1951 he was elected Fellow of the Royal Aeronautical Society.
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Bosutinib inhibited cells expressing a variety of mutations, some of which led to imatinib resistance, but the T315 mutation was completely resistant to bosutinib. In contrast to imatinib, nilotinib and dasatinib, bosutinib is not an efficient substrate for multidrug resistance (MDR) transporters that promotes efflux of foreign molecules from cells. Bosutinib even inhibits these transporter proteins in higher concentrations.
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It facilitates the efflux of accumulated Ca2+, disrupts the potential of the membrane and causes mitochondrial lumps. All of these effects bet on membrane fluidity. It's thought that agaric acid activates the opening of membrane pores due to the union of citrate to ADP transporters. However, a later research showed that N-ethylmaleimide inhibits carboxyatractyloside and agaric acid effects.
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For example, many monoamine releasing agents cause monoamine neurotransmitter efflux (i.e., the release of monoamine neurotransmitters from neurons into the synaptic cleft via monoamine transporter-mediated release) by triggering reverse transport at vesicular monoamine transporters (specifically, VMAT1 and VMAT2) and other monoamine transporters that are located along the plasma membrane of neurons (specifically, DAT, NET, and SERT).
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In June 2010 he along with American and Japanese colleagues had studied acid soils and discovered that certain species of crop plants are resistant to soluble aluminum. The way how they do, he explained, is that the genes of ALMT and MATE families encode membrane proteins which produce anion efflux called TaALMT1 across the cell membrane.
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While mild hypocalcemia is common after partial parathyroidectomy, some people experience persistently prolonged low calcium levels. This is called hungry bone syndrome. Despite the reactivation of unresected parathyroid glands producing normal to elevated levels of PTH, serum calcium continues to be low. The balance between calcium influx and efflux within the bone continues to be disrupted, favoring the former.
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CMRNG involves step wise mutation of penA, which codes for the penicillin-binding protein (PBP-2); mtr, which encodes an efflux pump that removes penicillin from the cell; and penB, which encodes the bacterial cell wall porins. PPNG involves the acquisition of a plasmid-borne beta- lactamase.Tapsall (2001) Antimicrobial resistance in Niesseria gonorrhoeae. World Health Organization.
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The energy coupling mechanisms for proteins of the FNT family have not been extensively characterized. HCO and NO uptakes may be coupled to H+ symport. HCO efflux may be driven by the membrane potential by a uniport mechanism or by H+ antiport. FocA of E. coli catalyzes bidirectional formate transport and may function by a channel-type mechanism.
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The intact endothelial lining inhibits platelet activation by producing nitric oxide, endothelial-ADPase, and PGI2 (prostacyclin). Endothelial-ADPase degrades the platelet activator ADP. Resting platelets maintain active calcium efflux via a cyclic AMP-activated calcium pump. Intracellular calcium concentration determines platelet activation status, as it is the second messenger that drives platelet conformational change and degranulation (see below).
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Thrombin is a potent platelet activator, acting through Gq and G12. These are G protein coupled receptors and they turn on calcium-mediated signaling pathways within the platelet, overcoming the baseline calcium efflux. Families of three G proteins (Gq, Gi, G12) operate together for full activation. Thrombin also promotes secondary fibrin-reinforcement of the platelet plug.
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'' Valspodar (PSC833) is an experimental cancer treatment and chemosensitizer. It is a derivative of ciclosporin D (cyclosporin D). Its primary use is as an inhibitor of the efflux transporter P-glycoprotein. Previous studies in animal models have found it to be effective at preventing cancer cell resistance to chemotherapeutics, but these findings did not translate to clinical success.
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The human dopamine transporter contains a high affinity extracellular zinc binding site which, upon zinc binding, inhibits dopamine reuptake and amplifies amphetamine-induced dopamine efflux in vitro. The human serotonin transporter and norepinephrine transporter do not contain zinc binding sites. Some EF-hand calcium binding proteins such as S100 or NCS-1 are also able to bind zinc ions.
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LysE appears to catalyze unidirectional efflux of L-lysine (and other basic amino acids such as L-arginine), and it provides the sole route for L-lysine excretion. The energy source is believed to be the proton motive force (H+ antiport). The E. coli ArgO homologue (TC# 2.A.75.1.2) effluxes arginine and possibly lysine and canavanine as well.
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Putative multidrug efflux transporters, detoxification proteins, extracytoplasmic sigma factors and PAS domain regulators are shown to have higher expression activity in presence of heavy metal. Cytochrome c class protein SO3300 also has an elevated transcription. For example, when reducing U(VI), special cytochromes such as MtrC and OmcA are used to form UO2 nanoparticles and associate it with biopolymers.
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Thus these cells have an influx transporter on one side and an efflux transporter on the other side of the cell to permit the effective transcellular transport of the nutrient. ArsA proteins are homologous to nitrogenase iron (NifH) proteins 2 of bacteria and to protochlorophyllide reductase iron sulfur ATP-binding proteins of cyanobacteria, algae and plants.
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Breast cancer resistance protein (BCRP) is a member of ATP-binding cassette (ABC) transporter proteins whose primary function is to efflux substrates bound to the plasma membrane. Impaired intestinal barrier functions play a major role in chronic low-grade inflammation (CLGI)-associated obesity, but the regulation of BCRP during obesity and its role in maintaining the intestinal barrier function during CLGI-associated obesity were unknown. Using several approaches, including efflux assays, immunoprecipitation/-blotting/-histochemistry, paracellular permeability assay, fluorescence activated cell sorting, cytokine assay, and immunofluorescence microscopy, recent studies suggest that obese individuals have compromised intestinal BCRP functions and that diet-induced obese mice recapitulate these outcomes. It was also demonstrated that the compromised BCRP functions during obesity were due to loss of Janus kinase 3 (JAK3)-mediated tyrosine phosphorylation of BCRP.
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Most stimulants exert their activating effects by enhancing catecholamine neurotranmission. Catecholamine neurotransmitters are employed in regulatory pathways implicated in attention, arousal, motivation, task salience and reward anticipation. Classical stimulants either block the reuptake or stimulate the efflux of these catecholamines, resulting in increased activity of their circuits. Some stimulants, specifically those with empathogenic and hallucinogenic effects, also affect serotonergic transmission.
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Amphetamine is a norepinephrine- dopamine releasing agent (NDRA). It enters neurons through dopamine and norepinephrine transporters and facilitates neurotransmitter efflux by activating TAAR1 and inhibiting VMAT2. At therapeutic doses, this causes emotional and cognitive effects such as euphoria, change in libido, increased arousal, and improved cognitive control. Likewise, it induces physical effects such as decreased reaction time, fatigue resistance, and increased muscle strength.
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Hyperpolarization is a change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization. It inhibits action potentials by increasing the stimulus required to move the membrane potential to the action potential threshold. Hyperpolarization is often caused by efflux of K+ (a cation) through K+ channels, or influx of Cl- (an anion) through Cl- channels.
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The fluids without a constant viscosity (non-Newtonian fluids) cannot be described by a single number. Non-Newtonian fluids exhibit a variety of different correlations between shear stress and shear rate. One of the most common instruments for measuring kinematic viscosity is the glass capillary viscometer. In coating industries, viscosity may be measured with a cup in which the efflux time is measured.
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These holds may be voiceless, voiced, or nasalized. Then lower the body of the tongue to rarefy the air above it. The closure at the front of the tongue is opened first, as the click "release"; then the closure at the back is released for the pulmonic or glottalic click "accompaniment" or "efflux". This may be aspirated, affricated, or even ejective.
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These modified compounds are then conjugated to polar compounds in phase II reactions. These reactions are catalysed by transferase enzymes such as glutathione S-transferases. Finally, in phase III, the conjugated xenobiotics may be further processed, before being recognised by efflux transporters and pumped out of cells. Drug metabolism often converts lipophilic compounds into hydrophilic products that are more readily excreted.
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Gliclazide selectively binds to sulfonylurea receptors (SUR-1) on the surface of the pancreatic beta-cells. It was shown to provide cardiovascular protection as it does not bind to sulfonylurea receptors (SUR-2A) in the heart. This binding effectively closes these K+ ion channels. This decreases the efflux of potassium from the cell which leads to the depolarization of the cell.
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Graded potentials that make the membrane potential more negative, and make the postsynaptic cell less likely to have an action potential, are called inhibitory post synaptic potentials (IPSPs). Hyperpolarization of membranes is caused by influx of Cl− or efflux of K+. As with EPSPs, the amplitude of the IPSP is directly proportional to the number of synaptic vesicles that were released.
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These transporters use ATP to efflux drugs out of the cell before they can exhibit their cytotoxic effects. Nanoparticles with MDR-1 silencing siRNA along with a cytotoxic drug PTX. Using this nanoparticle for delivery, silencing of the MDR-1 gene was achieved. Also, the cytotoxic effect of PTX was enhanced, probably due to an increase in intracellular drug accumulation.
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The Maharaja bequeathed vast amount of lands to the temple. A scholarly Brahmin community was established near the temple for its upkeep. However, with the exodus of the community shifting their place of residence to cities, and with efflux of time, the Temple did not receive adequate attention and proper maintenance. Further, the income from the properties that the Temple enjoyed started dwindling.
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Several bacterial sRNAs are involved in the regulation of genes that confer antibiotic resistance. For example, the sRNA DsrA regulates a drug efflux pump in E. coli, which is a system that mechanically pumps antibiotic out of bacterial cells. E. coli MicF also contributes to antibiotic resistance of cephalosporins, as it regulates membrane proteins involved in uptake of these class of antibiotics.
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Amphetamine is also a substrate for the presynaptic vesicular monoamine transporter, . Following amphetamine uptake at VMAT2, amphetamine induces the collapse of the vesicular pH gradient, which results in the release of dopamine molecules from synaptic vesicles into the cytosol via dopamine efflux through VMAT2. Subsequently, the cytosolic dopamine molecules are released from the presynaptic neuron into the synaptic cleft via reverse transport at .
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Potassium channel efflux is inhibited by magnesium. Thus hypomagnesemia results in an increased excretion of potassium in kidney, resulting in a hypokalaemia. This condition is believed to occur secondary to the decreased normal physiologic magnesium inhibition of the ROMK channels in the apical tubular membrane. In this light, hypomagnesemia is frequently the cause of hypokalaemic patients failing to respond to potassium supplementation.
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Some tumors, e.g. lung cancer, do not over-express this transporter but also are able to develop the resistance. It was discovered that another transporter MRP1 also work as the efflux pump, but in this case substrates are negatively charged natural compounds or drugs modified by glutathione, conjugation, glycosylation, sulfation and glucuronylation. Drugs can enter into a cell in few kinds of ways.
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As a consequence of DAT uptake, amphetamine and trace amines produce competitive reuptake inhibition at the transporter. Upon entering the presynaptic neuron, these compounds activate TAAR1 which, through protein kinase A (PKA) and protein kinase C (PKC) signaling, causes DAT phosphorylation. Phosphorylation by either protein kinase can result in DAT internalization ( reuptake inhibition), but phosphorylation alone induces reverse transporter function (dopamine efflux).
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The Plasma membrane Ca2+ ATPase PMCA4b is a putative receptor for extracellular renalase. The binding of renalase to PMCA4b stimulates calcium efflux with subsequent activation of the PI3K and MAPK pathways, increased expression of the anti-apoptotic factor Bcl-2, and decreased caspase3-mediated apoptosis. Administration of recombinant renalase protects against acute kidney injury (AKI), and against cardiac ischemia in animal models.
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Unlike ketamine and nitrous oxide, xenon does not stimulate a dopamine efflux in the nucleus accumbens. Like nitrous oxide and cyclopropane, xenon activates the two-pore domain potassium channel TREK-1. A related channel TASK-3 also implicated in the actions of inhalation anesthetics is insensitive to xenon. Xenon inhibits nicotinic acetylcholine α4β2 receptors which contribute to spinally mediated analgesia.
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The crystal structure of ArsA shows two other bound metalloid atoms, one liganded to Cys-172 and His-453, and the other liganded to His-148 and Ser-420. There is only a single high-affinity metalloid binding site in ArsA. Cys-172 controls the affinity of this site for metalloid and hence the efficiency of metalloactivation of the ArsAB efflux pump.
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Therefore, NR uptake is under NadR feedback control. ATP, not the proton motive force, appears to be required for NR uptake. Thus, the driving force for NR uptake via PnuC is NR phosphorylation by NadR. A concerted group translocation mechanism can be considered whereby NadR facilitates the dissociation of NR from PnuC by phosphorylating it to NMN, thus preventing efflux of NR.
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ESKAPE pathogens are differentiated from other pathogens due to their increased resistance to commonly used antibiotics such as penicillin, vancomycin, carbapenems, and more. This increased resistance, combined with the clinical significance of these bacteria in the medical field, results in a necessity to understand their mechanisms of resistance and combat them with novel antibiotics. Common mechanisms for resistance include the production of enzymes that attack the structure of antibiotics (for example, β-lactamases inactivating β-lactam antibiotics), modification of the target site that the antibiotic targets so that it can no longer bind properly, efflux pumps, and biofilm production. Efflux pumps are a feature of the membrane of Gram-negative bacteria that allows them to constantly pump out foreign material, including antibiotics, so that the inside of the cell never contains a high enough concentration of the drug to have an effect.
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Once freed from the soil the phosphorus compounds, primarily inorganic phosphate, are transferred through two proposed pathways. The first involves the active transport of inorganic phosphorus, primarily as phosphate through Pi(inorganic phosphorus) transporters out of the fungus into the interfacial apoplast, where it is protonated due to the acidic nature of the interfacial apoplast to form dihydrogen phosphate and then subsequently transferred through active Pi transporters into the plant cell. The second method relies on passive efflux of Pi from the fungus and active uptake by the plant, as in the prior pathway. It is observed that free living fungi ordinarily have very slight losses of Pi, thought to be due to the re-absorptive nature of the fungal hyphae, but it is proposed that during symbiosis the reabsorption of Pi is reduced thus increasing the net efflux out of the fungi.
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Palembang is an ethnically diverse city. The indigenous population in the region of Palembang are Malay people heavily influenced by Javanese culture. Many of them live in traditional settlements along the Musi River bank, although there has been a recent efflux of Malay to the outer suburbs. Many people of other ethnicities from other parts of South Sumatra and beyond also live in Palembang.
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The best-understood persistence factor is the E. coli high persistence gene, commonly abbreviated as hipA. Although tolerance is widely considered a passive state, there is evidence indicating it can be an energy-dependent process. Persister cells in E. coli can transport intracellular accumulations antibiotic using an energy requiring efflux pump called TolC. A persister subpopulation has also been demonstrated in budding yeast Saccharomyces cerevisiae.
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The CBS-pair domains dimerize and are a place of regulation through ATP- Mg2+ binding. Nucleotide binding leads to a change of the dimer conformation: from a twisted to a flat disc-like structure. This allows the efflux of Mg2+ between the extracellular matrix and the cytosolic matrix. CBS-1 is located between 318th and 379th aminoacid while CBS-2 is between the 386th and 452th.
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Measurement of short-term nutrient uptake rates in cranberry by aeroponics. Plant, Cell and Environment 19: 237–242. In their study, these researchers found that by measuring the concentrations and volumes of input and efflux solutions, they could accurately calculate the nutrient uptake rate (which was verified by comparing the results with N-isotope measurements). After verification of their analytical method, Barak et al.
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In Lambert–Eaton myasthenic syndrome, acetylcholine release is inhibited as antibodies involved in the host response against certain cancers cross-react with Ca2+ channels on the prejunctional membrane. Amifampridine works by blocking potassium channel efflux in nerve terminals so that action potential duration is increased. Ca2+ channels can then be open for a longer time and allow greater acetylcholine release to stimulate muscle at the end plate.
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Potassium buffering can be broadly categorized into two categories: Potassium uptake and Potassium spatial buffering. For potassium uptake, excess potassium ions are temporarily taken into glial cells through transporters, or potassium channels. In order to preserve electroneutrality, potassium influxes into glial cells are accompanied by influx of chlorine or efflux of sodium. It is expected that when potassium accumulates within glial cells, water influx and swelling occurs.
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Central nervous disorders are not uncommon, but the blood brain barrier (BBB) often blocks access of potential therapeutics to the brain. siRNAs that target and silence efflux proteins on the BBB surface have been shown to create an increase in BBB permeability. siRNA delivered via lipid based nanoparticles is able to cross the BBB completely. A huge difficulty in siRNA delivery is the problem of off-targeting.
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Both the ZTP and ZNT families, like the ZIP family, are zinc transporters.Persans, Michael W., Ken Nieman, and David E. Salt. "Functional activity and role of cation-efflux family members in Ni hyperaccumulation in Thlaspi goesingense." Proceedings of the National Academy of Sciences 98.17 (2001): 9995-10000 It has been observed in hyperaccumulating species, that these genes, specifically ZNT1 and ZNT2 alleles are chronically overexpressed.
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Once inside the cell, auxin cannot leave the cell on its own by crossing the lipid bilayer. Hence the export of auxin from the cell requires an active transport component in the plasma membrane - i.e. some membrane transport protein. Two protein families: The PIN proteins and ABCB (PGP proteins) transporters function as "auxin efflux carriers" and transport the anionic form of auxin out of the cell.
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The latter was thus demonstrated to be an autoreceptor on cells that release dopamine. TAAR1 is a presynaptic intracellular receptor that is also colocalized with DAT and which has the opposite effect of the D2 autoreceptor when activated; i.e., it internalizes dopamine transporters and induces efflux through reversed transporter function via PKA and PKC signaling. Surprisingly, DAT was not identified within any synaptic active zones.
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Naldemedine has a similar chemical structure as naltrexone but with an additional side chain that increases the molecular weight and polar surface area of the substance. Like naloxegol, naldemedine is a substrate of the P-glycoprotein efflux transporter. These properties result in less penetration into the CNS and decrease possible inference with the effects of opioid agonists. Naldemedine is a dual antagonist for MOR and DOR.
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The sharply dihedraled 'butterfly'-like twin rudder arrangement kept the tail surfaces clear of the jet efflux. The cockpit was completely faired into the fuselage contour, with a rounded clear nose-cone on the front of the aircraft. Behind this was the actual "window," a large armored-glass plate located some distance behind the extreme nose; the glazing extended almost to the wing root.
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In a hypotonic environment, cells will swell and eventually shrink; this shrinkage is due to efflux of taurine. This process also works in the opposite way in hypertonic environments. In hypertonic environments cells tend to shrink and then enlarge; this enlargement is due to an influx in taurine, effectively changing the osmotic pressure. This adaptation allows the flamingo to regulate between differences in salinity.
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Senicapoc (ICA-17043) is a Gardos channel blocker. It has been proposed for use in sickle cell anemia. Gardos channel blockers may work in the treatment of sickle cell anemia by blocking the efflux of potassium and water from red blood cells, thereby preventing the dehydration of red blood cells and stopping the polymerization of HbS. The Gardos channel has been identified as KCNN4.
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Bcr-Abl independent mechanisms include factors influencing the concentration of imatinib within the cell, for example by alterations in drug influx and efflux and activation of Bcr-Abl independent pathways, such as members of the Src kinase family. Imatinib resistance can also be produced by other mechanisms that will not be mentioned here as the importance of those mechanisms still remain a question due to lack of clinical data.
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An NMT H+ flux profile of Arabidopsis root across several zones. This example shows strong H+ influx closer to the root tip, and slight H+ efflux further from the tip. Non-invasive micro-test technology (NMT) is a scientific research technology used for measuring physiological events of intact biological samples. NMT is used for research in many biological areas such as gene function, plant physiology, biomedical research, and environmental science.
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They also moderately reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of the atrioventricular node (AV node). It also serves to slightly decrease the contractile forces of the ventricular muscle. M2 muscarinic receptors act via a Gi type receptor, which causes a decrease in cAMP in the cell, inhibition of voltage-gated Ca2+ channels, and increasing efflux of K+, in general, leading to inhibitory-type effects.
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Hypofrontality is a symptom of numerous neurological diseases defined as reduced utilization of glucose and blood flow in the prefrontal cortex. Hypofrontality can be difficult to detect under resting conditions, but under cognitive challenges, it has been seen to correlate with memory deficits along with executive function deficits. Hypofrontality is also linked to an increase in norepinephrine transmission and decrease in dopaminergic transmission with reduced dopamine efflux in the frontal cortex.
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Aconitine binds to the receptor at the neurotoxin binding site 2 on the alpha-subunit of the channel protein. This binding results in a sodium-ion channel that stays open longer. Aconitine suppresses the conformational change in the sodium-ion channel from the active state to the inactive state. The membrane stays depolarized due to the constant sodium influx (which is 10–1000 fold greater than the potassium efflux).
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Previously, glucagon was thought to activate HSL, however the removal of insulin's inhibitory effects ("cutting the brakes") is the source of activation. The lipolytic effect of glucagon in adipose tissue is minimal in humans. Another important role is the release of cholesterol from cholesteryl esters for use in the production of steroids and cholesterol efflux. Activity of HSL is important in preventing or ameliorating the generation of foam cells in atherosclerosis.
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This may cause the actin and myosin cross-bridges to separate prior to relaxation, ultimately causing greater tension on the remaining active motor units. This increases the risk of broadening, smearing, and damage to the sarcomere. When microtrauma occurs to these structures, nociceptors (pain receptors) within the muscle's connective tissues are stimulated and cause a sensation of pain. Another explanation for the pain associated with DOMS is the "enzyme efflux" theory.
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The mechanism underlying the effects of chloroquine on response to protease inhibitorsis inhibition of cellular drug efflux pumps. The effects of the antimalarial drugs, however, will require further evaluation before being clinically exploited. ; Grapefruit juice : Grapefruit juice is a common natural plant extract. The enzyme CYP3A4, a member of the Cytochrome P450 enzyme family, is present mostly in the liver but also in the lining of the gastrointestinal (GI) tract.
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Aliphatic, aromatic hydrocarbons and methane can be used as fuel in the humans' daily lives. In other words, these methanogens improve the coefficient of utilization. Moreover, these methanogens change the structure of the tailings pond and help the pore water efflux to be reused for processing oil sands. Because the archaea and bacteria metabolize and release bubbles within the tailings, the pore water can go through the soil easily.
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2-Methyl-3,4-methylenedioxyamphetamine (2-methyl-MDA) is an entactogen and psychedelic drug of the amphetamine class. It acts as a selective serotonin releasing agent (SSRA), with IC50 values of 93nM, 12,000nM, and 1,937nM for serotonin, dopamine, and norepinephrine efflux. 2-Methyl-MDA is more potent than MDA and 5-methyl-MDA. However, it is slightly more selective for serotonin over dopamine and norepinephrine release in comparison to 5-methyl- MDA.
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These enzymes are usually phosphorylate, acetylate, or adenylate drug compounds. #Drug efflux systems: The TB cell contains molecular systems that actively pump drug molecules out of the cell. #Mutations: Spontaneous mutations in the TB genome can alter proteins which are the target of drugs, making the bacteria drug resistant. One example is a mutation in the rpoB gene, which encodes the beta subunit of the bacteria's RNA polymerase.
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Acta Pathologica, Microbiologica et Immunologica Scandinavica 116:1001–1008 which would result in the antibiotic being unable to bind to its target # mutations in the promoter regions of mtr, resulting in the overexpression of genes that code for efflux pumps # mutations in the penB gene that encodes for the bacterial porin. This form of resistance has only been observed with ceftriaxone which is administered through an intramuscular injection.
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An example of secondary active transport The active transport of monoamines from the cytosol into storage vesicles operates against a large (>105) concentration gradient. Secondary active transport is the type of active transport used, meaning that VMAT1 is an antiporter. This transport is facilitated via proton gradient generated by the protein proton ATPase. The inward transport of the monoamine is coupled with the efflux of two protons per monoamine.
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Echinocandin resistance is rare among Candida spp. However, case studies have shown some resistance in C. albicans, C. glabrata, C. lusitaniae, C. tropicalis, and C. parapsilosis. Resistance patterns include alterations in the glucan synthase (Fks1-Fks2 complex), overexpression of efflux pumps, strengthening of cell wall by increased chitin production, upregulation of stress-response pathways, and dysregulation of mismatch repair pathways. In addition a few species and strains of Candida spp.
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Further, serum from individuals taking apabetalone had increased cholesterol efflux capacity, indicating the HDL generated in response to apabetalone functions in RCT. Inflammation is also a major contributor to atherosclerosis and CVD. Both ApoA-I induction and anti-inflammatory effects are common properties of BET inhibitors. In clinical trials, more favorable effects of apabetalone on coronary disease progression have been observed in patients with elevated levels of inflammatory markers.
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A unique member of the ArsB family is the rice silicon (silicate) efflux pump, Lsi2 (TC# 2.A.45.2.4). The silicon uptake systems, Lsi1 (TC# 1.A.8.12.2), and Lsi2 are expressed in roots, on the plasma membranes of cells in both the exodermis and the endodermis. In contrast to Lsi1, which is localized on the distal side, Lsi2 is localized on the proximal side of the same cells.
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The OXA group of β-lactamases occur mainly in Acinetobacter species and are divided into two clusters. OXA carbapenemases hydrolyse carbapenems very slowly in vitro, and the high MICs seen for some Acinetobacter hosts (>64 mg/L) may reflect secondary mechanisms. They are sometimes augmented in clinical isolates by additional resistance mechanisms, such as impermeability or efflux. OXA carbapenemases also tend to have a reduced hydrolytic efficiency towards penicillins and cephalosporins.
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Poloxamers have also been shown to inhibit MDR proteins and other drug efflux transporters on the surface of cancer cells; the MDR proteins are responsible for the efflux of drugs from the cells and hence increase the susceptibility of cancer cells to chemotherapeutic agents such as doxorubicin. Another effect of the polymers upon cancer cells is the inhibition of the production of ATP in multi-drug resistant (MDR) cancer cells. The polymers seem to inhibit respiratory proteins I and IV, and the effect on respiration seems to be selective for MDR cancer cells, which may be explained by the difference in fuel sources between MDR and sensitive cells (fatty acids and glucose respectively). The poloxamers have also been shown to enhance proto- apoptotic signaling, decrease anti-apoptoic defense in MDR cells, inhibit the glutathione/glutathione S-transferase detoxification system, induce the release of cytochrome C, increase reactive oxygen species in the cytoplasm, and abolish drug sequestering within cytoplasmic vesicles.
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There are 14 members of this protein subfamily in humans (called NLRP1 to NLRP14). NLRP3 and NLRP4 are responsible for the inflammasome activation. NLRP3 can be activated and give rise to NLRP3 inflammasome by ATP, bacterial pore-forming toxins, alum and crystals. Alongside the listed molecules, which lead to activation of NLRP3 inflammasome, the assembly and activation can also be induced by K+ efflux, Ca2+ influx, disruption of lysosomes and ROS originating from mitochondria.
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The Model 385 was designed and built under a United States Army research contract to prove a concept known as hot-cycle propulsion. The helicopter was given the military designation XV-9A with the serial number 64-15107. Two General Electric YT64-GE-6 turbojets were used as gas generators, the jet efflux was ducted to nozzles at the blade tips. The rotor blades also had cooling ducts in both the leading and trailing edges.
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A single cell can be adhered by means such as a polylysine-coated slide; this also works for other small samples like condensed organelles. Large tissue samples like roots may be weighted down with filter paper and resin tiles. Plenty of other large samples can be measured as well, such as organs or whole small organisms like zebrafish. An example of raw flux data unfolding as NMT measures oxygen efflux from a leaf sample.
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There are several sorts of cup – such as the Zahn cup and the Ford viscosity cup – with the usage of each type varying mainly according to the industry. The efflux time can also be converted to kinematic viscosities (centistokes, cSt) through the conversion equations. Also used in coatings, a Stormer viscometer uses load-based rotation in order to determine viscosity. The viscosity is reported in Krebs units (KU), which are unique to Stormer viscometers.
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3, the center view, Fig. 2, shows the cardinal feature of this trap, that it contains a collector for silt, sand, or sediment which is not, as in most other traps of the time, carried out through the valve with the efflux of water. A steam trap is a device used to discharge condensates and non-condensable gases with a negligible consumption or loss of live steam. Steam traps are nothing more than automatic valves.
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An inflow clepsydra A clepsydra is a clock that measures time by the flow of water. It consists of a pot with a small hole at the bottom through which the water can escape. The amount of escaping water gives the measure of time. As given by the Torricelli's law, the rate of efflux through the hole depends on the height of the water; and as the water level diminishes, the discharge is not uniform.
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Penicillin remains the drug of choice for treating streptococcal infections, and S. dysgalactiae strains with reduced susceptibility to penicillin have never been reported. Treatment duration varies from 5 days to 3 months, depending on the clinical diagnosis. Second-line agents include macrolides and clindamycin, although increasing resistance, due to both efflux and target modification, has been documented in some geographic regions. Aminoglycosides are not active against streptococci due to their lacking respiratory metabolism.
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Studies showing the influx of TRITC and efflux of ATP supports this hypothesis. In addition, arenicin-3 does not seem to induce cell lysis, which is important in the avoidance of sepsis during infection.Nielsen. Peptides that were translocated into the cell membrane then exert a secondary effect by inhibiting protein synthesis. It is hypothesized this mode of action is similar to that of tachyplesin I, which binds to the minor groove of DNA.
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There have also been prepared glycosides of silybin, which show better water solubility and even stronger hepatoprotective effect. Silymarin, like other flavonoids, has been shown to inhibit P-glycoprotein-mediated cellular efflux. The modulation of P-glycoprotein activity may result in altered absorption and bioavailability of drugs that are P-glycoprotein substrates. It has been reported that silymarin inhibits cytochrome P450 enzymes and an interaction with drugs primarily cleared by P450s cannot be excluded.
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Glutamate transporters (EAATs), which use the Na+/K+ gradient, reverse glutamate transport (efflux) in affected neurons and astrocytes, and depolarization increases downstream synaptic release of glutamate. In addition, cell death via lysis or apoptosis releases cytoplasmic glutamate outside of the ruptured cell. These two forms of glutamate release cause a continual cascade of excitotoxic cell death and further increased extracellular glutamate concentrations. Glutamate receptors' significance in excitotoxicity also links it to many neurogenerative diseases.
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P-glycoproteins are trans-membrane proteins that pump foreign substances out of cells in an ATP dependent fashion. Cancers overexpressing P-glycoproteins are able to pump out therapeutic molecules before they are able to reach their target, effectively making the cancer multi-drug resistant. Zosuquidar inhibits P-glycoproteins, inhibiting the efflux pump and restoring sensitivity to chemotherapeutic agents. Zosuqidar was initially characterized by Syntex Corporation, which was acquired by Roche in 1990.
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Potassium efflux from cardiac cells decreases action potential duration and results in non-uniform repolarization of the cardiac cells.Harris, A. S., Bisteni, A., Russell, R. A., Brigham, J. C., & Firestone, J. E. (1954). Excitory factors in ventricular tachycardia resulting from myocardial ischemia: potassium a major excitant. Science 119, 200−203 The heterogeneous repolarization of the cardiac tissue permits reentry of action potentials into conducting pathways, which manifests as malignant arrhythmias in the heart.
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In bacterial efflux systems, certain substances that need to be extruded from the cell include surface components of the bacterial cell (e.g. capsular polysaccharides, lipopolysaccharides, and teichoic acid), proteins involved in bacterial pathogenesis (e.g. hemolysis, heme-binding protein, and alkaline protease), heme, hydrolytic enzymes, S-layer proteins, competence factors, toxins, antibiotics, bacteriocins, peptide antibiotics, drugs and siderophores. They also play important roles in biosynthetic pathways, including extracellular polysaccharide biosynthesis and cytochrome biogenesis.
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An example is the secretion of hemolysin (HlyA) from E. coli where the inner membrane ABC transporter HlyB interacts with an inner membrane fusion protein HlyD and an outer membrane facilitator TolC. TolC allows hemolysin to be transported across the two membranes, bypassing the periplasm. Bacterial drug resistance has become an increasingly major health problem. One of the mechanisms for drug resistance is associated with an increase in antibiotic efflux from the bacterial cell.
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Similarly, all gaseous molecules emitted and received by plants such as plant hormones and other pheromones must pass the apoplast. In nitrate poor soils, acidification of the apoplast increases cell wall extensibility and root growth rate. This is believed to be caused by a decrease in nitrate uptake (due to deficit in the soil medium) and supplanted with an increase in chloride uptake. H+ATPase increases the efflux of H+, thus acidifying the apoplast.
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NAT2 is involved in the metabolism of xenobiotics, which can lead to both the inactivation of drugs and formation of toxic metabolites that can be carcinogenic. The biotransformation of xenobiotics may occur in three phases. In phase I, reactive and polar groups are introduced into the substrates. In phase II, conjugation of xenobiotics with charged species occurs, and in phase III additional modifications are made, with efflux mechanisms leading to excretion by transporters.
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The biophysical mechanism of presynaptic inhibition remains controversial. The presynaptic terminal has a distinct ionic composition that is high in chloride concentration which is largely due to cation-chloride cotransporters. Typically when GABA receptors are activated, it causes a chloride influx, which hyperpolarizes the cell. However, due to the high concentration of chloride at the presynaptic terminal and its altered reversal potential, GABA receptor activation actually causes a chloride efflux, and a resulting depolarization.
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Efflux pumps generally consist of an outer membrane protein, middle periplasmic protein, inner membrane protein, and transmembrane duct. The transmembrane duct is located in the outer membrane of the cell. The duct is also bound to two other proteins: a periplasmic membrane protein and an integral membrane transporter. The periplasmic membrane protein and the inner membrane protein of the system are coupled to control the opening and closing of the duct (channel).
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Prokaryotic and eukaryotic proteins cluster separately but may function with the same polarity by similar mechanisms. These proteins are secondary carriers which utilize the proton motive force (pmf) and function by H+ antiport (for metal efflux). One member, CzcD of Bacillus subtilis (TC# 2.A.4.1.3) , has been shown to exchange the divalent cation (Zn2+ or Cd2+ ) for two monovalent cations (K+ and H+ ) in an electroneutral process energized by the transmembrane pH gradient.
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Neurons are surrounded by extracellular fluid rich in sodium ions and poor in potassium ions. The concentrations of these ions are reversed inside the cells. Due to the difference in concentration, there is a chemical gradient across the cell membrane, which leads to sodium influx and potassium efflux. When the action potential takes place, a considerable change in extracellular potassium concentration occurs due to the limited volume of the CNS extracellular space.
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Human studies on pulmonary arteries have shown that normal, physiological inhibition of KCNB1 current aids vasoconstriction of arteries. In human pancreatic ß cells, KCNB1, which mediates potassium efflux, produces a downstroke of the action potential in the cell. In effect, this behavior halts insulin secretion, as its activation decreases the Cav channel-mediated calcium influx that is necessary for insulin exocytosis. KCNB1 has also been found to promote apoptosis within neuronal cells.
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Depiction of ATP synthase, the site of oxidative phosphorylation to generate ATP. The chemiosmotic coupling hypothesis, proposed by Nobel Prize in Chemistry winner Peter D. Mitchell, the electron transport chain and oxidative phosphorylation are coupled by a proton gradient across the inner mitochondrial membrane. The efflux of protons from the mitochondrial matrix creates an electrochemical gradient (proton gradient). This gradient is used by the FOF1 ATP synthase complex to make ATP via oxidative phosphorylation.
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In plants, the PIN proteins are integral membrane proteins that transport the anionic form of the phytohormone auxin across membranes. Most of the PIN proteins (e.g. PIN1/2/3/4/7 in the model plant Arabidopsis thaliana) localize at the plasma membrane (PM) where they serve as secondary active transporters involved in the efflux of auxin. The PM-localized PIN proteins show asymmetrical localisations on the membrane and are therefore responsible for polar auxin transport.
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P. citronellolis has also been found capable of the biosynthesis of polyhydroxyal-kanoates from "linear mono- and dicarboxylic acids", a type of bacterial-synthesized polyester. The P. citronellolis P3B5 genome contains genes that encode for six predicted lactamases that resist against lactam antibiotics. Furthermore, the genome contains genes encoding for efflux pumps that provide resistances to other antibiotics, such as trimethoprim. The P3B5 genome encodes genes that should enable it to degrade alkanes.
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Osmolytes are low-molecular weight organic compounds that influence the properties of biological fluids. Their primary role is to maintain the integrity of cells by affecting the viscosity, melting point, and ionic strength of the aqueous solution. When a cell swells due to external osmotic pressure, membrane channels open and allow efflux of osmolytes which carry water with them, restoring normal cell volume.Review of Medical Physiology, William F. Ganong, McGraw-Hill Medical, .
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Since dasatinib is an inhibitor of Src family kinases, it can overcome resistance due to Src family kinase activation. Because it does not bind to Bcr-Abl with the same stringent conformational requirements as imatinib, it can inhibit all Bcr-Abl kinase domain mutants except for T315I. Dasatinib is also not a substrate of multidrug P-glycoprotein efflux pumps like imatinib. Because of this dasatinib may be active in some patients after failure with both imatinib and nilotinib.
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Proton pump inhibitors (PPIs) block the gastric hydrogen potassium ATPase (H+/K+ ATPase) and inhibit gastric acid secretion. These drugs have emerged as the treatment of choice for acid-related diseases, including gastroesophageal reflux disease (GERD) and peptic ulcer disease. PPIs also can bind to other types of proton pumps such as those that occur in cancer cells and are finding applications in the reduction of cancer cell acid efflux and reduction of chemotherapy drug resistance.
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This condition is not responsive to typical therapies used in the treatment of PD, suggesting an alternative pathway than the typical dopaminergic loss within the substantia nigra. Manganese may accumulate in the basal ganglia, leading to the abnormal movements. A mutation of the SLC30A10 gene, a manganese efflux transporter necessary for decreasing intracellular Mn, has been linked with the development of this Parkinsonism-like disease. The Lewy bodies typical to PD are not seen in Mn-induced parkinsonism.
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In this case, the target prediction program enriched for targets directly connected to cancer progression such as steroid-5-alpha-reductase and synergistic targets like the efflux pump P-gp. These target-phenotype links can help identify novel MOAs. Beyond TCM and Ayurveda, chemogenomics can be applied early in drug discovery to determine a compound's mechanism of action and take advantage of genomic biomarkers of toxicity and efficacy for application to Phase I and II clinical trials.
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Resistance is a major cause of treatment failure in chemotherapeutic drugs. There are a few possible causes of resistance in cancer, one of which is the presence of small pumps on the surface of cancer cells that actively move chemotherapy from inside the cell to the outside. Cancer cells produce high amounts of these pumps, known as p-glycoprotein, in order to protect themselves from chemotherapeutics. Research on p-glycoprotein and other such chemotherapy efflux pumps is currently ongoing.
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Champagne Pool is a prominent geothermal feature within the Waiotapu geothermal area in the North Island of New Zealand. The terrestrial hot spring is located about southeast of Rotorua and about northeast of Taupo. The name Champagne Pool is derived from the abundant efflux of carbon dioxide (CO2), similar to a glass of bubbling champagne. The hot spring was formed 900 years ago by a hydrothermal eruption, which makes it in geological terms a relatively young system.
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Sirolimus is metabolized by the CYP3A4 enzyme and is a substrate of the P-glycoprotein (P-gp) efflux pump. It has an elimination half-life of 57–63 hours. The absorption of sirolimus into the blood stream from the intestine varies widely between patients, with some patients having up to eight times more exposure than others for the same dose. Drug levels are, therefore, taken to make sure patients get the right dose for their condition.
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The drugs, however, cannot move readily across the luminal membrane since it is a zwitterion. The cationic group (pyridinium ring) of the compound probably inhibits the efflux through the membrane. This results in an accumulation of cephaloridine in the renal cortex of the kidney, causing damage and necrosis of the S2 segment of the tubule. However, there are no adverse effects on renal function if serum levels of cephaloridine are maintained between 20 and 80 μg/ml.
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In the Middle Ages natural astrology was mainly focused on the diagnosis and the treatment of medical patients. For more information on this, see the article on medical astrology. An additional use would have been the application of astrology to determine future weather patterns based on the Aristotelian/Ptolemaic rationale that the planets cause change in the sublunary world by producing an efflux of elements and qualities. Every other branch was lumped together into the heading of 'judicial astrology'.
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Secondary metabolites of P. roqueforti, named andrastins A-D, are found in blue cheese. The andrastins inhibit proteins involved in the efflux of anticancer drugs from multidrug-resistant cancer cells. P. roqueforti also produces the neurotoxin roquefortine C. However, the levels of roquefortine c in cheese made from it is usually too low to produce toxic effects. The organism can also be used for the production of proteases and specialty chemicals, such as methyl ketones, including 2-heptanone.
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The statoliths are enmeshed in a web of actin and it is thought that their sedimentation transmits the gravitropic signal by activating mechanosensitive channels. The gravitropic signal then leads to the reorientation of auxin efflux carriers and subsequent redistribution of auxin streams in the root cap and root as a whole. The changed relations in concentration of auxin leads to differential growth of the root tissues. Taken together, the root is then turning to follow the gravity stimuli.
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Luciferase can act as an ATP sensor protein through biotinylation. Biotinylation will immobilize luciferase on the cell-surface by binding to a streptavidin-biotin complex. This allows luciferase to detect the efflux of ATP from the cell and will effectively display the real-time release of ATP through bioluminescence. Luciferase can additionally be made more sensitive for ATP detection by increasing the luminescence intensity by changing certain amino acid residues in the sequence of the protein.
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Slow afterhyperpolarisation (sAHP) refers to prolonged periods of hyperpolarisation in a neuron or cardiomyocyte following an action potential or other depolarising event. In neurons, trains of action potentials may be required to induce sAHPs; this is unlike fast AHPs that require no more than a single action potential. A variety of ionic mechanism may contribute to sAHPs, including potassium efflux from calcium-P. Sah, Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation.
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The 1920s and 1930s saw the price of silver appreciate in the international market, increasing the purchasing power of the Chinese currency and leading to a massive efflux of silver out of China. It became evident to the Chinese government that it could not retain the Silver Standard without debt defaults increasing, and so chose to abandon it. The situation was exacerbated by the multitude of commercial, provincial and foreign banks issuing currencies all at different values.
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It is possible that phototropins receive light and inhibit the activity of PINOID kinase (PID), which then promotes the activity of PIN3. This activation of PIN3 leads to asymmetric distribution of auxin, which then leads to asymmetric elongation of cells in the stem. pin3 mutants had shorter hypocotyls and roots than the wild-type, and the same phenotype was seen in plants grown with auxin efflux inhibitors. Using anti-PIN3 immunogold labeling, movement of the PIN3 protein was observed.
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In research, 1-N-Naphthylphthalamic acid (NPA) and 2,3,5-triiodobenzoic acid (TIBA) are used as specific inhibitors of the auxin efflux. Quercetin (a flavonol) and Genistein are naturally-occurring auxin transport inhibitors.p.435 Plant Physiology Third Edition Taiz and Zeiger (2002) 9-Hydroxyfluorene-9-carboxylic acid (HFCA), TIBA, and trans- cinnamic acid (TCA) are also example of Polar Auxin Transport Inhibitors. They prevent the development of the bilateral growth of the plant embryo during the globular stage.
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The efflux of potassium ions decreases the membrane potential or hyperpolarizes the cell. For small voltage increases from rest, the potassium current exceeds the sodium current and the voltage returns to its normal resting value, typically −70 mV. However, if the voltage increases past a critical threshold, typically 15 mV higher than the resting value, the sodium current dominates. This results in a runaway condition whereby the positive feedback from the sodium current activates even more sodium channels.
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A.3) which, as of early 2016, includes 20 different protein families. Most members of this transporter superfamily catalyze cation uptake and/or efflux, however one subfamily, the flippases, (TC# 3.A.3.8) is involved in flipping phospholipids to maintain the asymmetric nature of the biomembrane. In humans, P-type ATPases serve as a basis for nerve impulses, relaxation of muscles, secretion and absorption in the kidney, absorption of nutrient in the intestine and other physiological processes.
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The feedback cell releases a neurotransmitter to which the autoreceptor of the presynaptic neuron is receptive. The autoreceptor causes the inhibition of calcium channels (slowing calcium ion influx) and the opening of potassium channels (increasing potassium ion efflux) in the presynaptic membrane. These changes in ion concentration effectively diminish the amount of the original neurotransmitter released by the presynaptic terminal into the synaptic cleft. This causes a final depression on the activity of the postsynaptic neuron.
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Arsenite resistance (Ars) efflux pumps of bacteria may consist of two proteins, ArsB (TC# 2.A.45.1.1; the integral membrane constituent with twelve transmembrane spanners) and ArsA (TC# 3.A.4.1.1; the ATP-hydrolyzing, transport energizing subunit, as for the chromosomally-encoded E. coli system), or of one protein (just the ArsB integral membrane protein of the plasmid-encoded Staphylococcus system). ArsA proteins have two ATP binding domains and probably arose by a tandem gene duplication event.
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K+ is one ion that flows both into and out of the cell, causing a positive charge to develop. Malate is one of the main anions used to counteract this positive charge, and it is moved through the AtALMT6 ion channel. AtALMT6 is an aluminum-activated malate transporter that is found in guard cells, specifically in the vacuoles. This transport channel was found to cause either an influx or efflux of malate depending on the concentrations of calcium.
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Thus, the amount of CO2 produced through root respiration is determined by the root biomass and specific root respiration rates.Shibistova O, Lloyd J, Evgrafova S, Savushkina N, Zrazhevskaya G, Arneth A, Knohl A, Kolle O. (2002) Seasonal and spatial variability in soil CO2 efflux rates for a central Siberian Pinus sylvestris forest. Tellus 54B, 552-567. Directly next to the root is the area known as the rhizosphere, which also plays an important role in soil respiration.
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Bacteria that show no clinically relevant response to ertapenem include methicillin-resistant Staphylococcus species (including MRSA) as well as Acinetobacter, Aeromonas, Enterococcus, and Pseudomonas. Microorganisms can become resistant to ertapenem by producing carbapenemases, enzymes that inactivate the drug by opening the beta-lactam ring. Other mechanisms of resistance against carbapenems are development of efflux pumps that transport the antibiotics out of the bacterial cells, mutations of PBPs, and mutations of Gram-negative bacteria's porins which are necessary for carbapenems to enter the bacteria.
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Drug-resistant isolates remain an important hospital-acquired bacterial pathogen, add significantly to hospital stays, and are especially problematic in high-impact medical areas such as intensive care units. This antimicrobial resistance is thought to be attributable mainly to multidrug efflux pumps. The ability of K. pneumoniae to colonize the hospital environment, including carpeting, sinks, flowers, and various surfaces, as well as the skin of patients and hospital staff, has been identified as a major factor in the spread of hospital- acquired infections.
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Other viscometer types use balls or other objects. Viscometers that can characterize non-Newtonian fluids are usually called rheometers or plastometers. In the I.C.I "Oscar" viscometer, a sealed can of fluid was oscillated torsionally, and by clever measurement techniques it was possible to measure both viscosity and elasticity in the sample. The Marsh funnel viscometer measures viscosity from the time (efflux time) it takes a known volume of liquid to flow from the base of a cone through a short tube.
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The time of fall is a measure of viscosity, with the clearance between the piston and inside of the cylinder forming the measuring orifice. The viscosity controller measures the time of fall (time-of-fall seconds being the measure of viscosity) and displays the resulting viscosity value. The controller can calibrate the time-of-fall value to cup seconds (known as efflux cup), Saybolt universal second (SUS) or centipoise. Industrial use is popular due to simplicity, repeatability, low maintenance and longevity.
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The specificity is acquired by a two- residues combination (12 and 13 mer) in every tandem repeat that composes the central region; a change in a residue will result in a change of specificity towards a promoter. Finally, AAD is known as the cause of final transcription modulation, essential for virulence or avirulence. It has been recorded that Xam works with the activation of SWEET sugar transporters, promoting the efflux of glucose and sucrose to the apoplasm for bacterial benefit.
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9M317ME missiles can be fired at 2-second intervals, while its reaction (readiness) time is up to 10 s. The missile was designed to be single-staged, inertial guidance, radio control mid-course update and terminal semi-active radar homing. The tail surfaces have a span of 0.82 m when deployed after the missile leaves the launch container by a spring mechanism. Four gas-control vanes operating in the motor efflux turn the missile towards the required direction of flight.
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This change in ion concentration gradient causes the GABAA inhibitory current to surpass the reversal potential, leading to an efflux of the chloride ions. This leads to a decreased amplitude or even reversed polarity of the IPSPs. Metabotropic glutamate receptors (mGluRs) in the thalamocortical network have also shown to display some role in the generation of spike-and-wave discharges (SWDs) associated with absence epilepsy. The different subtypes of mGlu receptors have a modulatory role on either excitatory or inhibitory synaptic transmission.
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In contrast to calcein-AM, calcein has low permeability and therefore gets trapped in the cell and accumulates. As calcein-AM is an excellent substrate of the MDR1 and MRP1 efflux transporters, cells expressing MDR1 and/or MRP1 transporters pump the calcein-AM out of the cell before esterases can hydrolyze it. This results in a lower cellular accumulation rate of calcein. The higher the MDR activity is in the cell membrane, the less Calcein is accumulated in the cytoplasm.
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The hydrastine concentrations of goldenseal plants range between 1.5% and 5%, while the berberine concentrations are usually between 0.5% and 4.5%. Goldenseal is harvested for its rhizomes because the concentrations of hydrastine and berberine in the shoots do not meet these requirements. Berberine and hydrastine act as quaternary bases and are poorly soluble in water but freely soluble in alcohol. The herb seems to have synergistic antibacterial activity over berberine in vitro, possibly as a result of efflux pump inhibitory activity.
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Deletion of the GAT2 gene in mice does not appear to have any dramatic effects on brain function in a normal situation. The only difference noted so far is a slight elevation of brain Taurine levels. This was an unexpected finding, but is in agreement with the notion that GAT2 permits efflux of GABA and taurine from the brain to circulating blood through the blood brain barrier. GAT1 and GAT3 have higher concentrations in the brain and have higher affinity to GABA.
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Where grassland degradation has occurred, significant alterations to the carbon dioxide efflux during the non-growing season may take place. Both climate change and overgrazing factor into the degradation. As exemplified by the alpine wetland meadow on the Qinghai-Tibetan Plateau, there is the potential of being a moderate source of CO2 and a carbon sink, due to high soil organic content and low decomposition. The more the dynamics have been quantified, however, the effects of degradation become more tangible.
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The primary means of bacterial resistance to macrolides occurs by post-transcriptional methylation of the 23S bacterial ribosomal RNA. This acquired resistance can be either plasmid-mediated or chromosomal, i.e., through mutation, and results in cross-resistance to macrolides, lincosamides, and streptogramins (an MLS-resistant phenotype). Two other types of acquired resistance rarely seen include the production of drug- inactivating enzymes (esterases or kinases), as well as the production of active ATP-dependent efflux proteins that transport the drug outside of the cell.
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Methadone acts by binding to the µ-opioid receptor, but also has some affinity for the NMDA receptor, an ionotropic glutamate receptor. Methadone is metabolized by CYP3A4, CYP2B6, CYP2D6, and is a substrate, or in this case target, for the P-glycoprotein efflux protein, a protein which helps pump foreign substances out of cells, in the intestines and brain. The bioavailability and elimination half-life of methadone are subject to substantial interindividual variability. Its main route of administration is oral.
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Most proteins from the family have six transmembrane helices, but MSC2 of S. cerevisiae) and Znt5 and hZTL1 of H. sapiens have 15 and 12 predicted TMSs, respectively. These proteins exhibit an unusual degree of sequence divergence and size variation (300-750 residues). Eukaryotic proteins exhibit differences in cell localization. Some catalyze heavy metal uptake from the cytoplasm into various intracellular eukaryotic organelles (ZnT2-7) while others (ZnT1) catalyze efflux from the cytoplasm across the plasma membrane into the extracellular medium.
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This drug was specifically designed to treat brain tumors. Because of the blood brain barrier (BBB), many cancer therapy drugs are prevented from passing through the brain capillaries into the parenchyma. Paclitaxel is generally prevented from reaching its target in the cell due to the presence of the efflux pump P-glycoprotein (P-gp) at the barrier. This is known as a multidrug resistant-associated protein (MRP1) that causes resistance amongst many organic drugs that are not conjugated to acidic ligands.
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Cholera toxin interrupting regulation of adenyl cyclase inside the cell causing efflux of water and sodium into the intestinal lumen. V. cholerae pathogenicity genes code for proteins directly or indirectly involved in the virulence of the bacteria. To adapt the host intestinal environment and to avoid being attacked by bile acids and antimicrobial peptides, V. cholera used its outer membrane vesicles (OMVs). Upon entry, the bacteria sheds its OMVs, containing all the membrane modifications that make it vulnerable for the host attack.
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Noteworthy, the HMG-CoA reductase inhibitory activity appears to have a half-life of 20–30 hours, which is thought to be due to the active metabolites. Atorvastatin is also a substrate of the intestinal P-glycoprotein efflux transporter, which pumps the medication back into the intestinal lumen during medication absorption. In hepatic insufficiency, plasma concentrations of atorvastatin are significantly affected by concurrent liver disease. People with Child-Pugh Stage A liver disease show a four-fold increase in both Cmax and AUC.
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LDL contains apolipoprotein B (apoB), which allows LDL to bind to different tissues, such as the artery wall if the glycocalyx has been damaged by high blood sugar levels. If oxidised, the LDL can become trapped in the proteoglycans, preventing its removal by HDL cholesterol efflux. Normal functioning HDL is able to prevent the process of oxidation of LDL and the subsequent inflammatory processes seen after oxidation. Lipopolysaccharide, or LPS, is the major pathogenic factor on the cell wall of Gram-negative bacteria.
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The localization of some of the Pvd proteins in the periplasm and the outer membrane (such as PvdN, PvdO, PvdP, and PvdQ) have been interpreted to suggest that portions of the maturation of pyoverdine takes place in this location, perhaps after being transported into the periplasm by PvdE, which is homologous to ABC type exporters. How completely matured pyoverdine is exported from the cell remains unclear. Once completely matured, pyoverdine is exported from the periplasm by PvdRT-OpmQ efflux pump.
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The development of these agents was spurred by the increasing prevalence of bacteria resistant to tetracyclines. These agents were first synthesized in the early 1990s by making modifications to the tetracyclines. By adding a bulky N,N-dimethylglycylamido side chain to position 9 of minocycline, the compound became less susceptible to tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection. Further development of this initial work led to the creation of tigecycline, the first glycylcycline available for clinical use.
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Plant and fungal cells are also electrically excitable. The fundamental difference from animal action potentials is that the depolarization in plant cells is not accomplished by an uptake of positive sodium ions, but by release of negative chloride ions. An increase in cytoplasmic calcium ions may be the cause of anion release into the cell. This makes calcium a precursor to ion movements, such as the influx of negative chloride ions and efflux of positive potassium ions, as seen in barley leaves.
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NKCC1/2 will promote the influx of Na+, K+, and Cl− ions into the cell thereby causing the flow of water into the cell. In the reverse circumstances, where hypotonic (low extracellular Cl− ) conditions induce cell swelling, WNK1 is inhibited. Another cotransporter, KCC is inactive when phosphorylated; without activated WNK1, KCC does not undergo phosphorylation and can activate. The cotransporter will promote the efflux of K+ and Cl− ions and cause the flow of water out of the cell to combat swelling.
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The pumps remove drugs from tumor cells which lead to low drug concentration in the target, below therapeutic level. Efflux is caused by P-glycoprotein called also the multidrug transporter. This protein is a product of multidrug resistance gene MDR1 and a member of family of ATP-dependent transporters (ATP-binding cassette). P-glycoprotein occurs in every organism and serves to protect the body from xenobiotics and is involved in moving nutrients and other biologically important compounds inside one cell or between cells.
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In animals, it has been shown that different cell types maintain different concentrations of magnesium. It seems likely that the same is true for plants. This suggests that different cell types may regulate influx and efflux of magnesium in different ways based on their unique metabolic needs. Interstitial and systemic concentrations of free magnesium must be delicately maintained by the combined processes of buffering (binding of ions to proteins and other molecules) and muffling (the transport of ions to storage or extracellular spaces).
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The concern is that carbapenem is often used as a drug of last resort when battling resistant bacterial strains. New slight mutations could result in infections for which healthcare professionals can do very little, if anything, to treat patients with resistant organisms. A number of mechanisms cause carbapenem resistance in the Enterobacteriaceae. These include hyperproduction of ampC beta-lactamase with an outer membrane porin mutation, CTX-M extended-spectrum beta-lactamase with a porin mutation or drug efflux, and carbapenemase production.
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Ascorbic acid efflux by embryo of dicots plants is a well-established mechanism of iron reduction, and a step obligatory for iron uptake. All plants synthesize ascorbic acid. Ascorbic acid functions as a cofactor for enzymes involved in photosynthesis, synthesis of plant hormones, as an antioxidant and also regenerator of other antioxidants. Plants use multiple pathways to synthesize vitamin C. The major pathway starts with glucose, fructose or mannose (all simple sugars) and proceeds to L-galactose, L-galactonolactone and ascorbic acid.
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NLRP (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing), also abbreviated as NALP, is a type of NOD-like receptor. NLRP proteins are part of the innate immunity and detect conserved pathogen characteristics such as peptidoglycan. It is thought that NLRP proteins sense inherent danger, and link this with microbial products, creating a response under the concept of the inflammasome including K+ efflux and caspase 1 activation. NLRP is also known to be associated with a number of hereditary diseases.
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This process also relies on calcium channels, which depolarize the neuron by allowing an influx of calcium ions. So long as internal calcium ion concentrations remain at an elevated level, the neuron will continue to undergo periods of rapid spiking. However, elevated calcium ion levels also trigger a second messenger cascade within the cell which lower calcium influx and promote calcium efflux and buffering. As calcium concentrations decline, the period of rapid bursting ceases, and the phase of quiescence begins.
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Pseudomonas aeruginosa is a highly prevalent opportunistic pathogen. One of the most worrisome characteristics of P. aeruginosa is its low antibiotic susceptibility, which is attributable to a concerted action of multidrug efflux pumps with chromosomally encoded antibiotic resistance genes (e.g., mexAB-oprM, mexXY) and the low permeability of the bacterial cellular envelopes. P. aeruginosa has the ability to produce 4-hydroxy-2-alkylquinolines (HAQs) and it has been found that HAQs have prooxidant effects, and overexpressing modestly increased susceptibility to antibiotics.
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The properties of the Ca2+ pump SERCA and the channel IP3R present on the ER membrane facilitate feedback regulation coordinated by MAM function. In particular, the clearance of Ca2+ by the MAM allows for spatio-temporal patterning of Ca2+ signaling because Ca2+ alters IP3R activity in a biphasic manner. SERCA is likewise affected by mitochondrial feedback: uptake of Ca2+ by the MAM stimulates ATP production, thus providing energy that enables SERCA to reload the ER with Ca2+ for continued Ca2+ efflux at the MAM.
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Sotalol also acts on potassium channels and causes a delay in relaxation of the ventricles. By blocking these potassium channels, sotalol inhibits efflux of K+ ions, which results in an increase in the time before another electrical signal can be generated in ventricular myocytes. This increase in the period before a new signal for contraction is generated, helps to correct arrhythmias by reducing the potential for premature or abnormal contraction of the ventricles but also prolongs the frequency of ventricular contraction to help treat tachycardia.
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Doxorubicin (DOX) was conjugated with the tetrahedron and was loaded into MCF-7 breast cancer cells that contained the P-glycoprotein drug efflux pump. The results of the experiment showed the DOX was not being pumped out and apoptosis of the cancer cells was achieved. The tetrahedron without DOX was loaded into cells to test its biocompatibility, and the structure showed no cytotoxicity itself. The DNA tetrahedron was also used as barcode for profiling the subcellular expression and distribution of proteins in cells for diagnostic purposes.
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Aconitine can interact with the voltage-dependent sodium-ion channels, which are proteins in the cell membranes of excitable tissues, such as cardiac and skeletal muscles and neurons. These proteins are highly selective for sodium ions. They open very fast to depolarize the cell membrane potential, causing the upstroke of an action potential. Normally, the sodium channels close very rapidly, but the depolarization of the membrane potential causes the opening (activation) of potassium channels and potassium efflux, which results in repolarization of the membrane potential.
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All the ten Sefirot are linked one to the other, and every one of them has an active and a passive quality—emanating and receiving. The efflux of one Sefirah from another is symbolized in the form of the letters of the Hebrew alphabet. Thus the gimel (ג), shaped like a tube open at each end, represents a Sefirah, which receives strength at one end and discharges it at the other. The ten Sefirot are the energy of God, the forms in which His being manifests itself.
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During neurotransmitter reuptake, neurotransmitter transporters will move specific types of neurotransmitters from the extracellular space into the cytosol of a neuron or glial cell. When these transporters operate in reverse, they produce neurotransmitter efflux (i.e., the movement of neurotransmitters from the cytosol to the extracellular space via transporter-mediated release, as opposed to exocytotic release). In neurons, transporter reversal facilitates the release of neurotransmitters into the synaptic cleft, resulting in a higher concentration of synaptic neurotransmitters and increased signaling through the corresponding neurotransmitter receptors.
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When the electrophoretic force FE, oppositely directed to flow, overruns the hydrodynamic resistance force FW, the charged particles migrate from the filter medium, thus reducing significantly the thickness of the filter cake on the membrane. When the solid particles, subject to separation, are negatively charged they migrate towards the anode (positive pole) and deposit on the filter cloth situated there. As a result, on the cathode side’s membrane (negative pole) there is only a very thin film allowing nearly the whole filtrate to efflux through this membrane.
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This is similar in principle to the flow cups (efflux cups) like the Ford, Zahn and Shell cups which use different shapes to the cone and various nozzle sizes. The measurements can be done according to ISO 2431, ASTM D1200 - 10 or DIN 53411. The flexible-blade rheometer improves the accuracy of measurements for the lower-viscosity liquids utilizing the subtle changes in the flow field due to the flexibility of the moving or stationary blade (sometimes called wing or single-side-clamped cantilever).
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While the effect of editing on protein function is unknown, the developmental increase in editing does correspond to changes in function of the GABAA receptor. GABA binding leads to chloride channel activation, resulting in rapid increase in concentration of the ion. Initially, the receptor is an excitatory receptor, mediating depolarisation (efflux of Cl− ions) in immature neurons before changing to an inhibitory receptor, mediating hyperpolarisation (influx of Cl− ions) later on. GABAA converts to an inhibitory receptor from an excitatory receptor by the upregulation of KCC2 cotransporter.
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Hephaestin converts iron(II) state, Fe2+, to iron(III) state, Fe3+, and mediates iron efflux most likely in cooperation with the basolateral iron transporter, ferroportin 1. To a lesser extent hephaestin has been detected in colon, spleen, kidney, breast, placenta and bone trabecular cells but its role in these tissues remains to be established. Hephaestin presents homology with ceruloplasmin, a serum dehydrogenase protein involved in copper detoxification and storage. Hephaestin is a protein of 1135 aminoacids formed from a precursor of 1158 aminoacids and is 130.4 kDa.
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During later studies of interactions between diplopterol and lipid A in Methylobacterium extorquens, multidrug transport was found to be a hopanoid-dependent process. Squalene-hopene cyclase mutants derived from a wild type capable of multidrug efflux, a drug-resistance mechanism mediated by integral transport proteins, lost the ability to perform both multidrug transport and hopanoid synthesis. Researchers indicate this could be due to direct regulation of transport proteins by hopanoids or indirectly by altering membrane ordering in a way that disrupts the transport system.
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The Gram-negative, rod-shaped (bacillus) bacteria Pseudomonas aeurginosa is ubiquitous hydrocarbon degrader that is able to survive in extreme environments as well as in soil and many more common environments. Because of this versatility, it survives quite well in the lungs of patients suffering from late-stage cystic fibrosis (CF). It also benefits from the same previously mentioned Gram-negative resistance factors as A. baumannii. Mutants of P. aeurginosa with upregulated efflux pumps also exist that make finding an effective antibiotic or detergent incredibly difficult.
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The change in charge typically occurs due to an influx of sodium ions into a cell, although it can be mediated by an influx of any kind of cation or efflux of any kind of anion. The opposite of a depolarization is called a hyperpolarization. Usage of the term "depolarization" in biology differs from its use in physics, where it refers instead to situations in which any form of polarity (i.e. the presence of any electrical charge, whether positive or negative) changes to a value of zero.
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Through inhibiting potassium channels, budiodarone causes a decreased efflux of potassium out of the myocyte during the refractory period of its action potential, increasing the time it takes to reach the resting membrane potential. Through blocking sodium channels, budiodarone causes a decrease in sodium influx into myocytes during the depolarization period of its action potential. Through blocking calcium channels, budiodarone causes a decrease in calcium influx into myocytes, decreasing intracellular calcium and decreasing cardiac contractility, which is beneficial in preventing arrhythmias, but detrimental in ventricular contraction.
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Meadows can act as substantial sinks and sources of organic carbon, holding vast quantities of it in the soil. The fluxes of carbon depend mainly on the natural cycle of carbon uptake and efflux, which interplays with seasonal variations (e.g non-growing vs growing season). The wide range of meadow subtypes have in turn differing attributes (like plant configurations) affecting the area's ability to act as sinks; seagrass meadows are for instant identified as some of the more important sinks in the global carbon cycle.
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In molecular biology, an interactome is the whole set of molecular interactions in a particular cell. The term specifically refers to physical interactions among molecules (such as those among proteins, also known as protein–protein interactions, PPIs; or between small molecules and proteinsWang L, Eftekhari P, Schachner D, Ignatova ID, Palme V, Schilcher N, Ladurner A, Heiss EH, Stangl H, Dirsch VM, Atanasov AG. Novel interactomics approach identifies ABCA1 as direct target of evodiamine, which increases macrophage cholesterol efflux. Sci Rep. 2018 Jul 23;8(1):11061.
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Van Bambeke, Balzi, Tulkens (2000) Antibiotic Efflux Pumps. Biochemical Pharmacology 60:457–470 The cell wall of N. gonorrhoeae contains porins which are holes within the cell wall in which some molecules are able to diffuse into or out of the cell membrane. This mechanism falls under the first general mechanism for beta-lactam resistance. The penB gene encodes the porins for N. gonorrhoeae and when this gene undergoes mutations, there is a decrease in permeability of the cell wall to hydrophilic antibiotics like penicillin.
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The 1990-1994 Rwandan Civil War between rival social/ethnic groups (Hutu and Tutsi) turned deadly and produced a mass efflux of refugees. In Latin America, following the 1959 Cuban Revolution and the introduction of communism, over a million people have left Cuba. A new Jamaican diaspora formed around the start of the 21st century. More than 1 million Dominicans live abroad, a majority living in the US. A million Colombian refugees have left Colombia since 1965 to escape that country's violence and civil wars.
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Steady-state levels of anastrozole are achieved within 7 to 10 days of continuous administration, with 3.5-fold accumulation. However, maximal suppression of estradiol levels occurs within 3 or 4 days of therapy. Active efflux of anastrozole by P-glycoprotein at the blood–brain barrier has been found to limit the central nervous system penetration of anastrozole in rodents, whereas this was not the case with letrozole and vorozole. As such, anastrozole may have peripheral selectivity in humans, although this has yet to be confirmed.
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Other models assume that PIN proteins localise on the side of the cell where the efflux of auxin is the highest. These models are called "with-the-flux" models and explain the formation of vascular strands in leaves. The molecular mechanism responsible for these different behaviours of the system (with-the-flux and up-the- gradient) is not yet fully understood. Noticeably, an auxin receptor protein called ABP1 is thought to play a potentially significant role in the control of PIN proteins polarity by auxin.
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Blood glucose storage into Beta-cells lead to glycolysis and cause ATP generation. The elevated ATP/ adenosine diphosphate ratio causes closure of the KATP channel, and inhibit potassium efflux (a lot of potassium flows out of this channel), that leads to depolarization of the Beta-cell membrane. Depolarization is the loss of the difference in charge between the inner and outer parts of the plasma membrane of a muscle. This occurs because of change in permeability and migration of sodium ions inside the cell.
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Mutations in a single gene, ATP2A2, are responsible for the development of Darier’s disease. ATP2A2 encodes the SERCA2 protein, which is a calcium pump localized to the membranes of the endoplasmic reticulum (ER) in nearly all cells and the sarcoplasmic reticulum (SR) in muscle cells. The ER is where protein processing and transport begins for proteins targeted for secretion. The SR is a specialized form of ER found in muscle cells that sequesters calcium, the regulated efflux of which into the cytosol stimulates muscle fiber contraction.
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2) of Neisseria gonorrhoeae. The former protein is apparently cryptic in wild-type cells, but when expressed on a high copy number plasmid, or when expressed at higher levels due to mutation, it appeared to allow uptake (Km = 123 nM; see Michaelis–Menten kinetics) and subsequent utilization of p-aminobenzoyl- glutamate as a source of p-aminobenzoate for p-aminobenzoate auxotrophs. p-Aminobenzoate is a constituent of and a precursor for the biosynthesis of folic acid. MtrF was annotated as a putative drug efflux pump.
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Closed systems take short-term measurements (typically over few minutes only) in a chamber sealed over the soil. The rate of soil CO2 efflux is calculated on the basis of CO2 increased inside the chamber. As it is within the nature of closed chambers that CO2 continues to accumulate, measurement periods are reduced to a minimum to achieve a detectable, linear concentration increase, avoiding an excessive build-up of CO2 inside the chamber over time. Both individual assay information and diurnal CO2 respiration measuring information is accessible.
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Studies examining the role of pro- and anti-apoptotic factors support this model; for example, the anti-apoptotic factor Bcl-2 has been shown to interact with IP3Rs to reduce Ca2+ filling of the ER, leading to reduced efflux at the MAM and preventing collapse of the mitochondrial membrane potential post-apoptotic stimuli. Given the need for such fine regulation of Ca2+ signaling, it is perhaps unsurprising that dysregulated mitochondrial Ca2+ has been implicated in several neurodegenerative diseases, while the catalogue of tumor suppressors includes a few that are enriched at the MAM.
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At the time, it was considered that JM was AZT-insensitive due to poor phosphorylation. It later emerged that an AZT-efflux pump was the source of this poor AZT sensitivity. However, the conclusion remains valid that the diaryl phosphate was more able to retain activity in the JM cell line, and that this may imply a (small) degree of intracellular phosphate delivery. The electron-withdrawing power of the p-nitro groups and putative enhancements in aryl leaving group ability were suggested as the major driving force of this SAR.
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The system was essentially a bolt-on extension to the existing design and had almost no effect on the operation of the original engine. Each turbine blade was an integral part of a "blucket", the outboard section of which was a fan rotor blade. Running freely on a stub shaft, a series of buckets, mounted on a disc, made up the aft rotor assembly. The efflux from the turbojet expanded through the (inner) turbine annulus, thus providing power directly to the fan blades located in the outer annulus.
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Increased catecholamine levels promote positive lusitropy, enabling the heart to relax more rapidly. This effect is mediated by the phosphorylation of phospholamban and troponin I via a cAMP- dependent pathway. Catecholamine-induced calcium influx into the sarcoplasmic reticulum increases both inotropy and lusitropy. In other words, a quicker reduction in cytosolic calcium levels (because the calcium enters the sarcoplasmic reticulum) causes an increased rate of relaxation (+ lusitropy), however that also enables a greater degree of calcium efflux, back into the cytosol, when the next action potential arrives, thereby increasing inotropy as well.
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ACh binds to muscarinic receptors (M2) that are found principally on cells comprising the sinoatrial (SA) and atrioventricular (AV) nodes. Muscarinic receptors are coupled to the Gi- protein; therefore, vagal activation decreases cAMP. Gi-protein activation also leads to the activation of KACh channels that increase potassium efflux and hyperpolarizes the cells. Increases in vagal activities to the SA node decreases the firing rate of the pacemaker cells by decreasing the slope of the pacemaker potential (phase 4 of the action potential); this decreases heart rate (negative chronotropy).
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It is possible that channel blockade is maximal only when the channel is inhibited in its closed state. It appears that complete inactivation of Nav 1.7-mediated sodium efflux is necessary to upregulate enkephalin expression enough to achieve complete analgesia. Prior to the development of JNJ63955, the most potent [Nav 1.7] antagonists had failed in regards to achieving the same degree of analgesia as congenital Nav 1.7 inactivity. The proposed mechanism also suggests that the analgesic effects of Nav1.7 blockers may be greatly potentiated by the co-administration of exogenous opioids or enkephalinase inhibitors.
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From August 2007 the street was closed to private vehicles, leaving only buses, cycles and taxis allowed to access the whole street. The street is usually closed to all traffic every Friday and Saturday night to allow the efflux from night clubs and pubs located in that part of the street to clear. It is also closed when major events take place such as at the Millennium Stadium. The Prince Of Wales is a prominent J D Wetherspoon establishment at the junction with Wood Street, which leads to Central Station.
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Other studies have revealed a possible mutation on the calcium sensitive potassium (BK) channel. A mutation affecting the influx and efflux of potassium and calcium can cause large scale changes in a neuron. This specific mutation leads to increased excitability of the neuron, often inducing rapid depolarization eliciting numerous action potentials. The pathogenesis of PKND is partially defined by the identification of mutations in the myofibrillogenesis regulator 1 (MR-1), whose gene product is an enzyme involved in the detoxification of methylglyoxal (a compound present in coffee, cola, and alcoholic beverages).
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Some disconnected facts for arrangement: The Efflux chamber of the engine was made of nickel tubes brazed together through which flowed kerosene down one tube and back up the adjacent tube via a manifold at the mouth of the chamber. After static firings, these chambers were checked by climbing inside the engine from beneath. The mouth was in diameter but that of the throat was smaller, which restricted access to the inspector. In addition, during firing, the inside of the chamber became coated with fine carbon, making inspection a filthy procedure.
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Although (+)-totarol exhibits antimicrobial properties, the mode of action is unclear and various methods of inhibitory action have been proposed. In Staphylococcus aureus strains resistant to penicillin via creation of penicillin binding protein 2’ (PBP2’), (+)-totarol may inhibit the synthesis of PBP2’. (+)-Totarol may inhibit effluxing Staphylococcus aureus strains through inhibition of MsrA, although it is unclear if MsrA is an efflux pump. (+)-Totarol may also gain its antibacterial properties by inhibiting bacterial respiratory transportHaraguchi, H.; Ishikawa, H.; Sakai, S.; Ying, B. P.; Kubo, I. Experientia. 1996, 52, 573-576.
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Tangier disease is also linked to CL abnormalities. Tangier disease is characterized by very low blood plasma levels of High- Density Lipoprotein (HDL) cholesterol ("good cholesterol"), accumulation of cholesteryl esters in tissues, and an increased risk for developing cardiovascular disease. Unlike Barth syndrome, Tangier disease is mainly caused by abnormal enhanced production of CL. Studies show that there are three to fivefold increase of CL level in Tangier disease. Because increased CL levels would enhance cholesterol oxidation, and then the formation of oxysterols would consequently increase cholesterol efflux.
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Endomorphins maintain a variety of functions. Mechanistically, they bind inhibitory μ-opioid G-protein receptors, which act to close calcium ion channels and open potassium ion channels in the membranes of bound neurons. The elimination of calcium influx and facilitation of potassium ion efflux prevents neuronal depolarization, inhibits the generation of action potentials, and depresses the activity of excitatory neurons. In other instances, endomorphin binding causes excitation, where its activation of phospholipase C and adenylyl cyclase initiates an increase in calcium ion concentration, cellular depolarization, and the release of norepinephrine and serotonin.
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CEF scientists were able to provide new insights into the catalytic mechanism of ABC transporters. Based on real-time 31P-MAS-NMR they found that the homodimeric lipid A flippase MsbA is able to catalyze a reverse adenylate kinase-like reaction in addition to ATP hydrolysis. In addition, the ATP hydrolysis cycle of the ABC transporter LmrA was probed by site-directed spin labeling and pulsed electron–electron double resonance (PELDOR/DEER) spectroscopy . The secondary multidrug efflux pump EmrE from E. coli was extensively studied with 31P- and DNP-enhanced solid-state NMR. .
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The three main materials used in the infrared sensor are lead(II) sulfide (PbS), indium antimonide (InSb) and mercury cadmium telluride (HgCdTe). Older sensors tend to use PbS, newer sensors tend to use InSb or HgCdTe. All perform better when cooled, as they are both more sensitive and able to detect cooler objects. Nag missile with imaging infrared (IIR) seeker closeup Early infrared seekers were most effective in detecting infrared radiation with shorter wavelengths, such as the 4.2 micrometre emissions of the carbon dioxide efflux of a jet engine.
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Most often, the threshold potential is a membrane potential value between –50 and –55 mV, but can vary based upon several factors. A neuron's resting membrane potential (–70 mV) can be altered to either increase or decrease likelihood of reaching threshold via sodium and potassium ions. An influx of sodium into the cell through open, voltage-gated sodium channels can depolarize the membrane past threshold and thus excite it while an efflux of potassium or influx of chloride can hyperpolarize the cell and thus inhibit threshold from being reached.
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Most pharmaceutical research involving the BSCB aims to find efficient methods of overcoming its barrier mechanism to improve drug delivery. This can include directly bypassing the barrier, such as by placing a drug-eluting depot or injecting directly into the CNS, preventing efflux, such as with p-glycoprotein inhibitors, or by enhancing drug penetration.Chan GN, Evans RA, Banks DB, Mesev EV, Miller DS, Cannon RE. Selective induction of P-glycoprotein at the CNS barriers during symptomatic stage of an ALS animal model. Neurosci Lett. 2017 Feb 3;639:103-113.
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The ability of these channels to assume a closed-inactivated state causes the refractory period and is critical for the propagation of action potentials down an axon. Na+ channels both open and close more quickly than K+ channels, producing an influx of positive charge (Na+) toward the beginning of the action potential and an efflux (K+) toward the end. Ligand-gated sodium channels, on the other hand, create the change in the membrane potential in the first place, in response to the binding of a ligand to it.
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Potassium channels come in a variety of forms, are present in most eukaryotic cells, and typically tend to stabilize the cell membrane at the potassium equilibrium potential. As with sodium ions, graded potentials and action potentials are also dependent on potassium channels. While influx of Na+ ions into a neuron induce cellular depolarization, efflux of K+ ions out of a neuron causes a cell to repolarize to resting membrane potential. The activation of potassium ion channels themselves are dependent on the depolarization resulting from Na+ influx during an action potential.
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Development of resistance to one azole in this way will confer resistance to all drugs in the class. Another resistance mechanism employed by both C. albicans and C. glabrata is increasing the rate of efflux of the azole drug from the cell, by both ATP-binding cassette and major facilitator superfamily transporters. Other gene mutations are also known to contribute to development of resistance. C. glabrata develops resistance by up regulating CDR genes, and resistance in C. krusei is mediated by reduced sensitivity of the target enzyme to inhibition by the agent.
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The potassium ion channels are slower-acting than the sodium ion channels and so as the membrane potential starts to peak, the potassium ion channels open and causes an outflux of potassium to counteract the influx of sodium. At the peak, the outflux of potassium equals the influx of sodium, and the membrane does not change polarity. During repolarization, the sodium channels begin to become inactivated, causing a net efflux of potassium ions. This causes the membrane potential to drop down to its resting membrane potential of -100mV.
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Like other type II nuclear receptors, when activated, it forms a heterodimer with the retinoid X receptor, and binds to hormone response elements on DNA which elicits expression of gene products. One of the primary targets of PXR activation is the induction of CYP3A4, an important phase I oxidative enzyme that is responsible for the metabolism of many drugs. In addition, PXR up regulates the expression of phase II conjugating enzymes such as glutathione S-transferase and phase III transport uptake and efflux proteins such as OATP2 and MDR1.
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N. gonorrheoea has a high affinity for horizontal gene transfer, and as a result, the existence of any strain resistant to a given drug could spread easily across strains. Fluoroquinolones were a useful next-line treatment until resistance was achieved through efflux pumps and mutations to the gyrA gene, which encodes DNA gyrase. Third-generation cephalosporins have been used to treat gonorrhoea since 2007, but resistant strains have emerged. As of 2010, the recommended treatment is a single 250 mg intramuscular injection of ceftriaxone, sometimes in combination with azithromycin or doxycycline.
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The NorM efflux pump is a member of the MATE (multidrug and toxic compound extrusion) family and functions by a Na+ antiporter. It is also known that a point mutation upstream of the norM gene will causes overexpression of NorM, and mediate elevated resistance. High-level resistance to quinolones has been seen through target modification acting on the DNA gyrase and topoisomerase IV. Multiple amino acid substation mutations in the gyrA gene, which encodes for the DNA gyrase, have been seen extensively. DNA gyrase is an enzyme that binds to DNA and introduces negative supercoiling.
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It is also the fact that moving tumor cells display increased activity of anti-apoptotic genes, which causes resistance to chemotherapeutic drugs aimed at induction of programmed cell death. In addition, cells in the EMT state are known to also exhibit chemoresistance. This drug resistance is due to induction, during EMT, of the synthesis of the ABC family proteins responsible for the efflux of chemotherapeutic drugs out of the cell. The main transcription factors that trigger EMT and, at the same time, positively regulate the activity of ABC transporters include TWIST1, Snail, etc.
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The majority of the carbon dioxide, which is primarily produced by the oxidation of methane, that leaves the surface does so as CO2 efflux. By monitoring the groundwater plume, Bekins has shown that the degradation of benzene is coupled to the reduction of iron. She has monitored a hydrocarbon plume through measurements of the non-volatile dissolved carbon, and showed that over the course of twenty years it expanded by 20 m. Whilst most of this carbon has degraded around 200 m from the source, some remains up to 300 m away.
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One of the main conditions for GDP development (that is met in premature but not adult brain) is that GABA action on these stages should be excitatory rather than inhibitory. This is caused by a much higher concentration of Cl− concentration in the cytoplasm of neonatal neurons. Further, the expression of the chloride transporter, KCC2, is less in immature neurons, as a result of which there is the above-mentioned high intracellular chloride. On receiving a GABAergic stimulus, there is an efflux of Chloride from the cell, resulting in depolarization of the cell.
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When amphetamine binds to TAAR1, it reduces the firing rate of the postsynaptic neuron and triggers protein kinase A and protein kinase C signaling, resulting in DAT phosphorylation. Phosphorylated DAT then either operates in reverse or withdraws into the presynaptic neuron and ceases transport. When amphetamine enters the synaptic vesicles through VMAT2, dopamine is released into the cytosol. Amphetamine also produces dopamine efflux through a second TAAR1-independent mechanism involving CAMKIIα-mediated phosphorylation of the transporter, which putatively arises from the activation of DAT-coupled L-type calcium channels by amphetamine.
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In experiments conducted by Doyle et al., it was found that MCF-7, a breast adenomacarcinoma cell line, did not express the H19 gene; however a subline of MCF-7 with a multidrug resistance phenotype, MCF-7/AdrVp, had upregulation of H19. Curiously, mutant revertant MCF-7/AdrVp cells that lost their multidrug resistance and became drug- sensitive also lost H19 expression. Drug-resistant MCF-AdrVp cells do not overexpress P-glycoprotein, a cell membrane efflux pump commonly found in multidrug resistant cells; instead, they overexpress a 95kD membrane glycoprotein p95.
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The name non-canonical inflammasomes has its origin in the fact that these inflammasome complexes are independent of caspase-1. In mice, the non-canonical inflammasome is dependent on caspase-11 whereas human non-canonical inflammasomes rely on caspase 4 and caspase 5. All of these caspases are able to directly bind intracellular LPS and subsequently form macromolecular complexes mediating Gasdermin-D cleavage and induction of pyroptotic cell death. In addition, non-canonical inflammasomes may also indicrectly activate the NLRP3 inflammasome by triggering potassium efflux through memberane pores formed by Gasdermin-D.
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In the endothelial cells which line the inside of blood vessels, Ca2+ ions can regulate several signaling pathways which cause the smooth muscle surrounding blood vessels to relax. Some of these Ca2+-activated pathways include the stimulation of eNOS to produce nitric oxide, as well as the stimulation of Kca channels to efflux K+ and cause hyperpolarization of the cell membrane. Both nitric oxide and hyperpolarization cause the smooth muscle to relax in order to regulate the amount of tone in blood vessels.Christopher J Garland, C Robin Hiley, Kim A Dora.
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TAAR1 is an intracellular receptor expressed within the presynaptic terminal of monoamine neurons in humans and other animals. In model cell systems, hTAAR1 has extremely poor membrane expression. A method to induce hTAAR1 membrane expression has been used to study its pharmacology via a bioluminescence resonance energy transfer cAMP assay. Because TAAR1 is an intracellular receptor in monoamine neurons, exogenous TAAR1 ligands must enter the presynaptic neuron through a membrane transport protein or be able to diffuse across the presynaptic membrane in order to reach the receptor and produce reuptake inhibition and neurotransmitter efflux.
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In a study, normal goat muscle fibers could be made myotonic by blocking the chloride conductance using myotonia inducing drugs, or by substituting in an anion that is unable to pass through a semi-permeable membrane. Isolated intercostal muscle from goats with the condition was shown to be significantly different than that of normal goats in terms of the temperature dependence of the resting membrane resistance and potassium efflux.Lipicky, R. J., & Bryant, S. H. (1972). Temperature effects on cable parameters and K efflux in normal and myotonic goats.
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Similarly, the N-terminus of the human XPR1 protein binds directly to the beta subunit of the G-protein heterotrimer, leading to increased production of cAMP. Thus, this domain is involved in G-protein associated signal transduction. The N-termini of several proteins involved in the regulation of phosphate transport, including the putative phosphate level sensors, Pho81 from Saccharomyces cerevisiae and NUC-2 from Neurospora crassa, have this domain. The SPX domains of the S. cerevisiae low-affinity phosphate transporters, Pho87 and Pho90, auto-regulate uptake and prevent efflux.
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Avian erythrocytes (red blood cells) have been shown to contain approximately ten times the amount of taurine (an amino acid) as mammal erythrocytes. Taurine has a fairly large list of physiological functions; but in birds, it can have an important influence on osmoregulation. It helps the movement of ions in erythrocytes by altering the permeability of the membrane and regulating osmotic pressure within the cell. The regulation of osmotic pressure is achieved by the influx or efflux of taurine relative to changes in the osmolarity of the blood.
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Monoamine releasing agents can have a wide variety of effects depending upon their selectivity for monoamines. Selective serotonin releasing agents such as fenfluramine and related compounds are described as dysphoric and lethargic in lower doses, and in higher doses some hallucinogenic effects have been reported. Less selective serotonergic agents that stimulate an efflux in dopamine, such as MDMA are described as more pleasant, increasing energy, sociability and elevating mood. Dopamine releasing agents, usually selective for both norepinephrine and dopamine have psychostimulant effect, causing an increase in energy, and elevated mood.
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The delayed rectifier potassium ion current is largely responsible for the repolarization of ventricular cardiac myocytes by permitting potassium efflux. DATS causes a decrease in the steady-state inactivation, alters deactivation, and impairs trafficking of the hERG channel from the endoplasmic reticulum to the plasma membrane of the cell. This decreases the amount of functional potassium ion rectifier channels on the cell membrane and thus, slows depolarization. However, hERG trafficking impairment has also been shown to cause arrhythmias due to the development of long QT syndrome and should be considered in drug development.
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Glyoxylate is involved in the development of hyperoxaluria, a key cause of nephrolithiasis (commonly known as kidney stones). Glyoxylate is both a substrate and inductor of sulfate anion transporter-1 (sat-1), a gene responsible for oxalate transportation, allowing it to increase sat-1 mRNA expression and as a result oxalate efflux from the cell. The increased oxalate release allows the buildup of calcium oxalate in the urine, and thus the eventual formation of kidney stones. The disruption of glyoxylate metabolism provides an additional mechanism of hyperoxaluria development.
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Cisplatin combination chemotherapy is the cornerstone of treatment of many cancers. Initial platinum responsiveness is high but the majority of cancer patients will eventually relapse with cisplatin-resistant disease. Many mechanisms of cisplatin resistance have been proposed including changes in cellular uptake and efflux of the drug, increased detoxification of the drug, inhibition of apoptosis and increased DNA repair. Oxaliplatin is active in highly cisplatin-resistant cancer cells in the laboratory; however, there is little evidence for its activity in the clinical treatment of patients with cisplatin-resistant cancer.
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Vesicular transporters rely on a proton gradient created by the hydrolysis of adenosine triphosphate (ATP) in order to carry out their work: v-ATPase hydrolyzes ATP, causing protons to be pumped into the synaptic vesicles and creating a proton gradient. Then the efflux of protons from the vesicle provides the energy to bring the neurotransmitter into the vesicle. Neurotransmitter transporters frequently use electrochemical gradients that exist across cell membranes to carry out their work. For example, some transporters use energy obtained by the cotransport, or symport, of Na+ in order to move glutamate across membranes.
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A pharmacogenomic genome-wide association study (GWAS) reported that patients from the dal-OUTCOMES study bearing a protective allele at SNP rs1967309 in the ADCY9 gene may have benefited from dalcetrapib therapy. Changes in inflammation and cholesterol efflux capacity may in part explain the benefits associated with the protective genotype. The Dal-GenE trial is currently validating these observations. This clinical trial is a randomized placebo- controlled study to evaluate the effects of dalcetrapib on cardiovascular risk in patients with recent acute coronary syndrome bearing the protective genotype.
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A full agonist of VGSC site two, batrachotoxin, was then used to determine to what extent hoiamide A acted as an agonist. The experiments demonstrated that hoiamide A is a partial agonist because the maximum sodium influx hoiamide A binding caused was less than that of batrachotoxin. The chemical structure of hoiamide A and B Another study found that hoiamide A stimulated capspase-3 activity, lactic acid dehydrogenase efflux, and nuclear condensation. These processes are specifically and uniquely involved in necrosis and apoptosis, suggesting that hoiamide A is involved neuronal death by both necrosis and apoptosis.
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Because C. perfringens beta toxin shares homology with S. aureus pore-forming alpha toxin, it was hypothesized that beta toxin acts in a similar way. Upon investigation, it was found that C. perfringens beta toxin forms cation-selective pores in cell membranes of 1.6-1.8 nm and results in swelling and lysis in HL60 cells. Treatment of these cells with beta toxin induces an efflux of K+ and influxes of Ca2+, Cl− and Na+. Heat-stable beta- toxin oligomers are shown to bind to cell membranes of human umbilical vein endothelial cells; endothelial cells are beta toxin's primary target, upon introduction.
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Paterson and Portnoy went on to work with biotech companies to develop vaccines for both cancer and infectious disease applications. Numerous clinical trials based on their discoveries have shown promising results as immunotherapeutic treatments for cancer. In 1997, Dr Portnoy moved to UC Berkeley where his lab continues to examine fundamental aspects of L. monocytogenes biology, and has expanded to focus on both innate and acquired immunity in the context of Listeria infection. Dr. Portnoy and collaborators have shown that immune cells recognize cyclic di-AMP, a novel and essential bacterial signaling molecule, secreted by L. monocytogenes through multidrug resistance efflux transporters.
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For long distances, relocation occurs via the stream of fluid in phloem vessels, but, for short-distance transport, a unique system of coordinated polar transport directly from cell to cell is exploited. This short-distance, active transport exhibits some morphogenetic properties. This process, polar auxin transport, is directional, very strictly regulated, and based in uneven distribution of auxin efflux carriers on the plasma membrane, which send auxins in the proper direction. While PIN-FORMED (PIN) proteins are vital in transporting auxin in a polar manner, the family of AUXIN1/LIKE-AUX1 (AUX/LAX) genes encodes for non-polar auxin influx carriers.
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Probably the most notable feature is the extensive eelgrass population at the tideland perimeter of Richardson Bay. This eelgrass occurrence in Richardson Bay is considered one of the most sizeable stands in Northern California, and it is being restored, leading to further extent of this habitat. There is an extensive pickleweed habitat at the western end of the bay, where many acres of mudflat areas are exposed to shorebirds at low tide at the efflux of Pickleweed Inlet. Upland plants found at the perimeter of Richardson's Bay include toyon, coast live oak, California bay, and native California bunch grasses.
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TFMPP has affinity for the 5-HT1A (Ki = 288 nM), 5-HT1B (Ki = 132 nM), 5-HT1D (Ki = 282 nM), 5-HT2A (Ki = 269 nM), and 5-HT2C (Ki = 62 nM) receptors, and functions as a full agonist at all sites except the 5-HT2A receptor, where it acts as a weak partial agonist or antagonist. Unlike the related piperazine compound meta-chlorophenylpiperazine (mCPP), TFMPP has insignificant affinity for the 5-HT3 receptor (IC50 = 2,373 nM). TFMPP also binds to the SERT (EC50 = 121 nM) and evokes the release of serotonin. It has no effects on dopamine or norepinephrine reuptake or efflux.
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The first of the Type 42 class, Sheffield, was initially fitted with the odd-looking "Mickey Mouse" ears on her funnel tops which were in fact exhaust deflectors - "Loxton bends" - for the Rolls Royce Olympus TM1A gas turbines, to guide the high-temperature exhaust efflux sidewards and minimise damage to overhead aerials. As this provided a prominent target for then-new infrared homing missiles, only Sheffield and the next two in the class the Argentinian Hércules and Santísima Trinidad had these 'ears'. Sheffield was the only one of her class to be not fitted with STWS II triple anti-submarine torpedo tubes.
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Bents Basin is a protected nature reserve and state park near Wallacia, New South Wales, Australia in the Sydney metropolitan area. The lake basin, which formed at the efflux of the Nepean River from the Hawkesbury Sandstone (Sydney sandstone) gorge, is a popular swimming hole with a camping area and an education centre used by local school groups. Also featuring a large woodland area and native wildlife, the reserve is the only picnic area along the Nepean River and it is one of the most popular water-based picnic parks in Greater Western Sydney.Craven, P.J. (1983).
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The cumulative effect of volume-changes in these motor cells manifests itself on the tissue/organ level as a swelling or shrinking of one or both sides of the pulvinus, which results in the reorientation of the adjacent leaf. Potassium and chloride have been shown to be the major osmolytes involved in the process, and plasma membrane-located proton pumps and ion transporters have been shown to play a critical role in creating osmotic potential.Suh, S., Moran, N. and Lee, Y. (2000) Blue light activates potassium-efflux channels in flexor cells from Samanea saman motor organs via two mechanisms. Plant Physiol.
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When the normal balance between inhibition and excitation is significantly disrupted in all or part of the brain, a seizure can occur. The GABA system is an important target for anticonvulsant drugs, since seizures may be discouraged by increasing GABA synthesis, decreasing its breakdown, or enhancing its effect on neurons. The nerve impulse is characterised by a great influx of sodium ions through channels in the neuron's cell membrane followed by an efflux of potassium ions through other channels. The neuron is unable to fire again for a short time (known as the refractory period), which is mediated by another potassium channel.
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Angptl3 also acts as dual inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL), thereby increasing plasma triglyceride, LDL cholesterol and HDL cholesterol in mice and humans. ANGPTL3 inhibits endothelial lipase hydrolysis of HDL-phospholipid (PL), thereby increasing HDL-PL levels. Circulating PL-rich HDL particles have high cholesterol efflux abilities. Angptl3 plays a major role in promoting uptake of circulating triglycerides into white adipose tissue in the fed state, likely through activation by Angptl8, a feeding-induced hepatokine, to inhibit postprandial LPL activity in cardiac and skeletal muscles, as suggested by the ANGPTL3-4-8 model.
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Kay, p. Previous design efforts in Germany had investigated ducted fans (turbofans / by-pass turbojets) and contra-rotating compressor spools, but Leist incorporated both into the ZTL6000 (precursor to the ZTL 6001 / DB 007), resulting in a very complex design. Another novel feature was a turbine which passed alternately through the combustion chamber efflux and cooling air tapped from the bypass flow. By the Summer of 1942 design goals had been revised down and the new engine was given the designations ZTL6001 (company) and DB 007 / ZTL 109-007 (RLM), ZTL being an acronym for Zweikreiststurbinen-Luftstrahltriebwerk (two-circuit turbojet engine).
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His areas of expertise includes a major contribution to the discovery of P-glycoprotein (MDR1, ABCB1), the multidrug resistance efflux transporter associated with clinical resistance to anti-cancer agents... In 2007, he reported for the first time in Science magazine that silent polymorphisms can impact on the tertiary structure and function of a protein.. Gottesman is an elected member of the American Association for the Advancement of Science (1988), the National Academy of Medicine (2003), the Association of American Physicians (2006), the American Academy of Arts and Sciences (2010), and the National Academy of Sciences (2018).
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The onset of skeletal muscle activity is associated with the initiation and propagation of action potentials again associated with an efflux of K+ to the extracellular fluid and transverse tubule system. When many action potentials are elicited subsequently more K+ is expelled from the cell into the transverse tubular system. As K+ accumulates in the transverse tubular system the equilibrium potential for K+ (EK+) normally around -80 mV, becomes more depolarized (depolarization), according to the Nernst equation. In skeletal muscle fibers the equilibrium potential for Cl− is around -80 mV, equal to that of K+ at rest.
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In contrast to glutamate, the neurotransmitter GABA mainly functions to trigger inhibitory postsynaptic potentials (IPSPs) in vertebrates. The binding of GABA to a postsynaptic receptor causes the opening of ion channels that either cause an influx of negatively charged chloride ions into the cell or an efflux of positively charged potassium ions out of the cell. The effect of these two options is the hyperpolarization of the postsynaptic cell, or IPSP. Summation with other IPSPs and contrasting EPSPs determines whether the postsynaptic potential will reach threshold and cause an action potential to fire in the postsynaptic neuron.
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Hunter Rouse (March 29, 1906 – October 16, 1996) was a hydraulician known for his research on the mechanics of fluid turbulence. Rouse was a faculty member at the Massachusetts Institute of Technology, Cambridge, from 1929 until 1933, when he moved to Columbia University. He was at the California Institute of Technology, Pasadena (1936–1939), and in 1939 he joined the staff of the University of Iowa, Iowa City, where he was dean of the College of Engineering from 1966 to 1972. His work includes hydraulic studies of similitude, efflux and overflow, jet diffusion, boundary roughness, and sediment suspension.
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Kornberg had been awarded the Nobel Prize for discovering pol I, then believed to be the mechanism of bacterial DNA replication, although in this experiment he showed that pol III was the actual replicative machinery. NEM activates ouabain-insensitive Cl-dependent K efflux in low K sheep and goat red blood cells.A chloride dependent K+ flux induced by N ethylmaleimide in genetically low K+ sheep and goat erythrocytes.P.K. Lauf and B.E. Theg. Biochem. Biophys. Res. Comm., 92:1422, 1980 This discovery contributed to the molecular identification of K-Cl cotransport (KCC) in human embryonic cells transfected by KCC1 isoform cDNA, 16 years later.
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Lipid vesicles or liposomes are approximately spherical pockets that are enclosed by a lipid bilayer. These structures are used in laboratories to study the effects of chemicals in cells by delivering these chemicals directly to the cell, as well as getting more insight into cell membrane permeability. Lipid vesicles and liposomes are formed by first suspending a lipid in an aqueous solution then agitating the mixture through sonication, resulting in a vesicle. By measuring the rate of efflux from that of the inside of the vesicle to the ambient solution, allows researcher to better understand membrane permeability.
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The ykkC/yxkD leader is a conserved RNA structure found upstream of the ykkC and yxkD genes in Bacillus subtilis and related genes in other bacteria. The function of this family is unclear for many years although it has been suggested that it may function to switch on efflux pumps and detoxification systems in response to harmful environmental molecules. The Thermoanaerobacter tengcongensis sequence AE013027 overlaps with that of purine riboswitch suggesting that the two riboswitches may work in conjunction to regulate the upstream gene which codes for TTE0584 (Q8RC62), a member of the permease family. Nelson et al.
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The yybP-ykoY leader RNA element was originally discovered in E. coli during a large scale screen and was named SraF. This family was later found to exist upstream of related families of protein genes in many bacteria, including the yybP and ykoY genes in B. subtilis. The specific functions of these proteins are unknown, but this structured RNA element may be involved in their genetic regulation as a riboswitch. The yybP-ykoY element was later proposed to be manganese-responsive after another associated family of genes, YebN/MntP, was shown to encode Mn2+ efflux pumps in several bacteria.
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This increases serotonin signaling, which according to the hypothesis is believed to elevate mood and thus relieve depressive symptoms. This proposal for the antidepressant mechanism of serotonin reuptake inhibitors does not account for the time course of the therapeutic effect, which takes weeks to months, while transporter inhibition is essentially immediate. The net effect of amphetamine (AMPH) use is an increase of dopamine, norepinephrine and serotonin in the synapse. It has been shown that AMPH acts upon trace amine-associated receptor 1 (TAAR1) to induce efflux and reuptake inhibition in the serotonin, norepinephrine, and dopamine transporters.
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V. cholerae in the intestinal lumen utilizes the TCP to attach to the intestinal mucosa, not invading the mucosa. After doing so it secretes cholerae toxin causing its symptoms. This then increases cyclic AMP or cAMP by binding (cholerae toxin) to adenylyl cyclase activating the GS pathway which leads to efflux of water and sodium into the intestinal lumen causing watery stools or rice watery stools. V. cholerae can cause syndromes ranging from asymptomatic to cholera gravis. In endemic areas, 75% of cases are asymptomatic, 20% are mild to moderate, and 2-5% are severe forms such as cholera gravis.
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The Cierva W.9 showing the long tailboom from which the efflux from the engine-driven fan emerged from a directable vent on the left side at the tip of the tailboom The use of directed air to provide anti-torque control had been tested as early as 1945 in the British Cierva W.9. During 1957, a Spanish prototype designed and built by Aerotecnica flew using exhaust gases from the turbine instead of a tail rotor. This model was designated as Aerotecnica AC-14. Development of the NOTAR system dates back to 1975, when engineers at Hughes Helicopters began concept development work.
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Calcium entry through the CRAC channel is promoted by potassium efflux through the Kv1.3 and KCa3.1 potassium channels. Blockade of Kv1.3 channels in effector-memory T cells suppresses calcium signaling, cytokine production (interferon-gamma, interleukin 2) and cell proliferation. In vivo, Kv1.3 blockers paralyze effector-memory T cells at the sites of inflammation and prevent their reactivation in inflamed tissues. In contrast, Kv1.3 blockers do not affect the homing to and motility within lymph nodes of naive and central memory T cells, most likely because these cells express the KCa3.1 channel and are, therefore, protected from the effect of Kv1.3 blockade.
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A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons. SSRAs have been used clinically as appetite suppressants, and they have also been proposed as novel antidepressants and anxiolytics with the potential for a faster onset of action and superior efficacy relative to the selective serotonin reuptake inhibitors (SSRIs). A closely related type of drug is a serotonin reuptake inhibitor (SRI).
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As a consequence the economy depended heavily on the timely afflux and efflux of these metals. So Venice had to develop a highly flexible system of currencies and change rates between coins consisting of silver and gold, if it wanted to preserve and enhance its role as platform and turntable of international trading. In addition the change rates between the currencies circulating within Venice and outside had to be adjusted adequately. On the other hand, the nobility had hardly any scruples to force its colonies to accept change rates, which were only useful for the fisk.
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Falcarindiol is a polyyne found in carrot roots which has antifungal activity. Falcarindiol is the main compound responsible for bitterness in carrots. Falcarindiol and other falcarindiol-type polyacetylenes are also found in many other plants of the family Apiaceae, including some commonly used seasonings such as dill and parsley. A variety of bioactivities have been reported so far for falcaridiol and the falcarindiol-type polyacetylenes,Wang L, Palme V, Schilcher N, Ladurner A, Heiss EH, Stangl H, Bauer R, Dirsch VM, Atanasov AG. The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein Stability.
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Proteins in the outer membrane efflux protein family form trimeric (three- piece) channels that allow export of a variety of substrates in gram-negative bacteria. Each member of this family is composed of two repeats. The trimeric channel is composed of a 12-stranded beta-barrel that spans the outer membrane, and a long all helical barrel that spans the periplasm. Examples include the Escherichia coli TolC outer membrane protein, which is required for proper expression of outer membrane protein genes; the Rhizobium nodulation protein; and the Pseudomonas FusA protein, which is involved in resistance to fusaric acid.
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Both YdaH and MtrF are bowl-shaped dimers with a solvent-filled basin extending from the cytoplasm halfway across the membrane bilayer. The protomers of YdaH and MtrF contain nine transmembrane helices and two hairpins which suggested a plausible pathway for substrate transport. A combination of the crystal structure, genetic analyses and substrate accumulation assays indicated that both YdaH and MtrF behave as exporters, capable of removing the folate metabolite p-aminobenzoic acid from bacterial cells. In fact, it was shown that both YdaH and MtrF participate as antibiotic efflux pumps, mediating bacterial resistance to sulfonamide antimetabolite drugs.
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The binding of the ligand (odor molecule or odorant) to the receptor leads to an action potential in the receptor neuron, via a second messenger pathway, depending on the organism. In mammals, the odorants stimulate adenylate cyclase to synthesize cAMP via a G protein called Golf. cAMP, which is the second messenger here, opens a cyclic nucleotide-gated ion channel (CNG), producing an influx of cations (largely Ca2+ with some Na+) into the cell, slightly depolarising it. The Ca2+ in turn opens a Ca2+-activated chloride channel, leading to efflux of Cl−, further depolarizing the cell and triggering an action potential.
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This down-regulation is believed to be in response to oxygen levels. TspO works through (or modulates) the PpsR/AppA system and acts upstream of the site of action of these regulatory proteins. It has been suggested that the TspO regulatory pathway works by regulating the efflux of certain tetrapyrrole intermediates of the haem/bacteriochlorophyll biosynthetic pathways in response to the availability of molecular oxygen, thereby causing the accumulation of a biosynthetic intermediate that serves as a corepressor for the regulated genes. A homologue of the TspO protein in Sinorhizobium meliloti is involved in regulating expression of the ndi locus in response to stress conditions.
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Wilson disease protein is associated with ATP7B gene, approximately 80 Kb, located on human chromosome 13 and consists of 21 exons. The mRNA transcribed by ATP7B gene has a size of 7.5 Kb, and which encodes a protein of 1465 amino acids. The gene is a member of the P-type cation transport ATPase family and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least two putative copper-binding sites. This protein functions as a monomer, exporting copper out of the cells, such as the efflux of hepatic copper into the bile.
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The protons are effluxed at a region on the sides of the tube that corresponds to the location of the intracellular alkaline band. Energy is required for pollen tube growth and an H+-ATPase may mediate the efflux. Hepler has shown that the magnitude of the intracellular calcium and proton gradients and the extracellular fluxes of these ions oscillate with a period of 15-50 s. This period is identical to the period of oscillation in the rate of pollen tube growth, however, the intracellular calcium peak follows the growth rate peak by 1-4 seconds, and the extracellular calcium peak follows the growth rate peak by 11-15 seconds.
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In April 2011, the WHO stated that resistance to the most effective antimalarial drug, artemisinin, could unravel national Indian malaria control programs, which have achieved significant progress in the last decade. WHO advocates the rational use of antimalarial drugs and acknowledges the crucial role of community health workers in reducing malaria in the region. Two main mechanisms of resistance drive Plasmodium resistance to antimalarial drugs. The first one is an efflux of the drug away from its action site due to mutations in different transporter genes (like pfcrt in chloroquine resistance) or an increased number of the gene copies (like pfmdr1 copy number in mefloquine resistance).
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Competent S. pneumoniae can also secrete an enzyme (murein hydrolase) that destroys non-competent cells (fratricide) causing DNA to be released into the surrounding medium for potential use by the competent cells. The insect antimicrobial peptide cecropin A can destroy planktonic and sessile biofilm-forming uropathogenic E. Coli cells, either alone or when combined with the antibiotic nalidixic acid, synergistically clearing infection in vivo (in the insect host Galleria mellonella) without off-target cytotoxicity. The multi-target mechanism of action involves outer membrane permeabilization followed by biofilm disruption triggered by the inhibition of efflux pump activity and interactions with extracellular and intracellular nucleic acids.
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Furthermore, it was noted that the application of an electric field resulted in the migration of the tumor cells. Using vibrating probe, the electrical currents involved in the biological processes occurring at leaves have been measured. Through vibrating probe it has been possible to correlate electrical currents with the stomatal aperture, suggesting that stomatal opening was related to proton efflux. Based on this work further vibrating probe measurements also indicated a relationship between the photosynthetic activity of a plant and the flow of electrical current on its leaf surfaces, with the measured current changing when it was exposed to different types of light and dark.
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TRK transporters, responsible for the bulk of K+ accumulation in plants, fungi, and bacteria, mediate ion currents driven by the large membrane voltages (-150 to -250 mV) common to non-animal cells. Bacterial TRK proteins resemble K+ channels in their primary sequence, crystallize as membrane dimers having intramolecular K+-channel-like folding, and complex with a cytoplasmic collar formed of four RCK domains. Fungal TRK proteins possess a large built- in regulatory domain and a highly conserved pair of transmembrane helices (TMSs 7 and 8, ahead of the C-terminus), postulated to facilitate intramembranal oligomerization.These fungal HAK proteins are chloride channels mediating efflux, a process suppressed by osmoprotective agents.
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Class B carbapenemases are metallolactamases and require a zinc at the active site for hydrolysis. # A clinical isolate of E. coli from the sputum sample of a patient admitted to a Beijing hospital was found to acquire resistance to carbapenem through mutations not previously observed. It involved a mutation of a regulator gene marR and the expression of a normally nontranslated membrane porin yedS; both mutations were demonstrated to have effects on the ability of this strain of E.coli to resist carbapenems. The strain lacked the outer membrane proteins OmpF and OmpC, and showed increased expression of a multidrug efflux pump, but did not produce carbapenemase.
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Sheffield with the prominent exhaust deflectors on her funnel The first of class, Sheffield, was initially fitted with the odd-looking "Mickey Mouse" ears on her funnel tops which were in fact exhaust deflectors - "Loxton bends" - for the Rolls Royce Olympus TM1A gas turbines, to guide the high-temperature exhaust efflux sidewards and minimise damage to overhead aerials. As this provided a prominent target for then-new infrared homing missiles, only Sheffield and both the Argentinian Hércules and Santísima Trinidad had these 'ears'. All subsequent Olympus and Tyne uptakes were fitted with 'cheese graters' which mixed machinery space vent air with the engine exhaust to reduce infrared signatures.
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Pendrin is an ion exchanger found in many types of cells in the body. High levels of pendrin expression have been identified in the inner ear and thyroid. In the thyroid, pendrin mediates a component of the efflux of iodide across the apical membrane of the thyrocyte, which is critical for the formation of thyroid hormone. The exact function of pendrin in the inner ear remains unclear; however, pendrin may play a role in acid-base balance as a chloride-bicarbonate exchanger, regulate volume homeostasis through its ability to function as a chloride-formate exchanger or indirectly modulate the calcium concentration of the endolymph.
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Drug discrimination studies showed that 5-methyl-MDA substitutes for MDA, MMAI, and LSD, but not amphetamine, suggesting that it produces a mix of entactogen and hallucinogenic effects without any stimulant effects. 5-Methyl- MDA acts as a selective serotonin releasing agent (SSRA) with IC50 values of 107nM, 11,600nM, and 1,494nM for serotonin, dopamine, and norepinephrine efflux. It is over 5 times more potent than MDA in vitro assays, with a suitable active dose possibly in vivo being around 15–25 mg. Subsequent testing in vivo, however, has found that it is not as potent as once thought and is active at at least 100 mg.
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Mammalian cells have two major groups of zinc transporter proteins; the ones that export zinc from the cytoplasm to the extracellular space (efflux), which are called ZnT (SLC30 family) , and ZIP (SLC39 family) proteins whose functions are in the opposite direction (influx). ZIP family proteins are named as Zrt- and Irt-like proteins because of their similarities to Zrt and Irt proteins which are respectively zinc and iron -regulated transporter proteins in yeast and Arabidopsis that were discovered earlier than ZIP and ZnT proteins. ZIP family consists of four subfamilies (I, II, LIV-1, and gufA), and ZIP9 is the only member of subfamily I.
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Acinetobacter species are innately resistant to many classes of antibiotics, including penicillin, chloramphenicol, and often aminoglycosides. Resistance to fluoroquinolones has been reported during therapy, which has also resulted in increased resistance to other drug classes mediated through active drug efflux. A dramatic increase in antibiotic resistance in Acinetobacter strains has been reported by the Centers for Disease Control and Prevention (CDC), and the carbapenems are recognised as the gold-standard and treatment of last resort. Acinetobacter species are unusual in that they are sensitive to sulbactam, which is commonly used to inhibit bacterial beta-lactamase, but this is an example of the antibacterial property of sulbactam itself.
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Efflux transporter- expressing cells actively pump substrates out of the cell, which results in a lower rate of substrate accumulation, lower intracellular concentration at steady state, or a faster rate of substrate elimination from cells loaded with the substrate. Transported radioactive substrates or labeled fluorescent dyes can be directly measured, or in an indirect set up, the modulation of the accumulation of a probe substrate (e.g. fluorescent dyes like rhodamine 123, or calcein) can be determined in the presence of a test drug. Calcein-AM, A highly permeable derivative of calcein readily penetrates into intact cells, where the endogenous esterases rapidly hydrolyze it to the fluorescent calcein.
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This testing can be done using several methods which generally involve taking samples of water, or passing large amounts of water through a filter to sample bacteria, then testing to see if bacteria from that water grow on selective media such as MacConkey agar. Alternatively, the sample can be tested to see if it utilizes various nutrients in ways characteristic of coliform bacteria. Coliform bacteria selected as indicators of faecal contamination must not persist in the environment for long periods of time following efflux from the intestine, and their presence must be closely correlated with contamination by other faecal organisms. Indicator organisms need not be pathogenic.
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HR is triggered by the plant when it recognizes a pathogen. The identification of a pathogen typically occurs when a virulence gene product, secreted by a pathogen, binds to, or indirectly interacts with the product of a plant R gene. R genes are highly polymorphic, and many plants produce several different types of R gene products, enabling them to recognize virulence products produced by many different pathogens. In phase one of the HR, the activation of R genes triggers an ion flux, involving an efflux of hydroxide and potassium to the outside the cells, and an influx of calcium and hydrogen ions into the cells.
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Tetracyclines are a class of antibiotics that inhibit protein synthesis by binding to the 30s ribosomal subunit of bacterial cells, keeping transcription of the bacterial genome from occurring. Tetracyclines are bacteriostatic, which means that the growth of the bacterium will be slowed. Tetracyclines are not often recommended for the treatment of N. gonorrhoeae because the treatment regimen requires many doses, which may affect compliance and contribute to resistance. Tetracycline is still used as treatment for this infection in developing countries because the cost for the drug is low As with the penicillin resistance, the penB (porin formation) and mtr (efflux pump formation) mutations mediate chromosomal resistance.
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Bacterial efflux transporters are classified into five major superfamilies, based on their amino acid sequence and the energy source used to export their substrates: # The major facilitator superfamily (MFS) # The ATP-binding cassette superfamily (ABC) # The small multidrug resistance family (SMR) # The resistance-nodulation-cell division superfamily (RND) # The multi antimicrobial extrusion protein family (MATE). Of these, only the ABC superfamily are primary transporters, the rest being secondary transporters utilizing proton or sodium gradient as a source of energy. Whereas MFS dominates in Gram positive bacteria, the RND family was once thought to be unique to Gram negative bacteria. They have since been found in all major kingdoms.
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The key to the rhythmic firing of pacemaker cells is that, unlike other neurons in the body, these cells will slowly depolarize by themselves and do not need any outside innervation from the autonomic nervous system to fire action potentials. As in all other cells, the resting potential of a pacemaker cell (-60mV to -70mV) is caused by a continuous outflow or "leak" of potassium ions through ion channel proteins in the membrane that surrounds the cells. However, in pacemaker cells, this potassium permeability (efflux) decreases as time goes on, causing a slow depolarization. In addition, there is a slow, continuous inward flow of sodium, called the "funny" or pacemaker current.
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The Escherichia coli Acriflavine resistance (acrA and acrB genes) encode a multi-drug efflux system that is believed to protect the bacterium against hydrophobic inhibitors. The E. coli AcrB protein is a transporter that is energized by proton-motive force and that shows the widest substrate specificity among all known multidrug pumps, ranging from most of the currently used antibiotics, disinfectants, dyes, and detergents to simple solvents. The structure of ligand-free AcrB shows that it is a homotrimer of 110kDa per subunit. Each subunit contains 12 transmembrane helices and two large periplasmic domains (each exceeding 300 residues) between helices 1 and 2, and helices 7 and 8.
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With higher frequency stimulation, higher plateau of depolarization was observed. Therefore, they hypothesized that the potassium released to extracellular compartment during axonal activity entered and depolarized nearby astrocytes, where it was transported away by unfamiliar mechanism, which caused depolarization on astrocytes distant from site of stimulation. The proposed model was actually inappropriate since at the time neither gap junctions nor syncytium among glial cells were known, and optic nerve of Necturus are unmyelinated, which means that potassium efflux occurred directly into the periaxonal extracellular space, where potassium ions in extracellular space would be directly absorbed into the abundant astrocytes around axons.Kofuji, P. and E. A. Newman (2004).
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BK channels are activated (opened) by changes in membrane electrical potential and/or by increases in concentration of intracellular calcium ion (Ca2+). Opening of BK channels allows K+ to passively flow through the channel, down the electrochemical gradient. Under typical physiological conditions, this results in an efflux of K+ from the cell, which leads to cell membrane hyperpolarization (a decrease in the electrical potential across the cell membrane) and a decrease in cell excitability (a decrease in the probability that the cell will transmit an action potential). BK channels are essential for the regulation of several key physiological processes including smooth muscle tone and neuronal excitability.
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These adapted cells have been studied to better understand their greater efficiency of membrane transport (efflux of drugs). Mucor racemosus can biotransform lipids like 4-ene-3-one steroids and 20(S)-Protopanaxatriol into several different products, some of which have anticancer properties (as the metabolites resulted in increased intracellular calcium ion content, leading to cell cycle arrest and apoptosis). Two of the products formed from this biotransformation are two novel hydroperoxylated metabolites that have been shown to be effective against prostate cancer cells. Secondary metabolites of M. racemosus do not exhibit genotoxic activity, and the species is not known to be a producer of mycotoxins.
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The inside of a neuron has a negative charge, relative to the cell exterior, from the movement of K+ out of the cell. The neuron membrane is more permeable to K+ than to other ions, allowing this ion to selectively move out of the cell, down its concentration gradient. This concentration gradient along with potassium leak channels present on the membrane of the neuron causes an efflux of potassium ions making the resting potential close to EK ≈ –75 mV. Since Na+ ions are in higher concentrations outside of the cell, the concentration and voltage differences both drive them into the cell when Na+ channels open.
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Preliminary evidence suggests that the dopamine transporter couples to L-type voltage-gated calcium channels (particularly Cav1.2 and Cav1.3), which are expressed in virtually all dopamine neurons. As a result of DAT–Cav coupling, DAT substrates that produce depolarizing currents through the transporter are able to open calcium channels that are coupled to the transporter, resulting in a calcium influx in dopamine neurons. This calcium influx is believed to induce CAMKII-mediated phosphorylation of the dopamine transporter as a downstream effect; since DAT phosphorylation by CAMKII results in dopamine efflux in vivo, activation of transporter-coupled calcium channels is a potential mechanism by which certain drugs (e.g., amphetamine) trigger neurotransmitter release.
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Apolipoprotein A1 is the major protein component of HDL particles in plasma. Chylomicrons secreted from the intestinal enterocyte also contain apo A1, but it is quickly transferred to HDL in the bloodstream. The protein, as a component of HDL particles, enables efflux of fat molecules by accepting fats from within cells (including macrophages within the walls of arteries which have become overloaded with ingested fats from oxidized LDL particles) for transport (in the water outside cells) elsewhere, including back to LDL particles or to the liver for excretion. It is a cofactor for lecithin cholesterolacyltransferase (LCAT) which is responsible for the formation of most plasma cholesteryl esters.
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Goodell received her B.Sc. at Imperial College of Science and Technology in London, England in 1986 with Honors. She went on to earn her Ph.D. at University of Cambridge in 1991. She completed postdoctoral fellowships in Richard Mulligan’s lab at the prestigious Whitehead Institute for Biomedical Research at Massachusetts Institute of Technology and Harvard Medical School. At MIT, she developed a novel method for isolating blood- forming stem cells from mouse bone marrow based on a fortuitous observation that stem cells efflux fluorescent lipophillic dyes. This “side population (SP)” method has become widely used to isolate stem cells from a variety of species and adult tissues, including from cancer stem cells.
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Probable cation-transporting ATPase 13A2 is an enzyme that in humans is encoded by the ATP13A2 gene that is involved in the transport of divalent transition metal cations. It appears to protect cells from manganese and zinc toxicity, possibly by causing cellular efflux and/or lysosomal sequestration; and from iron toxicity, possibly by preserving lysosome integrity against iron-induced lipid peroxidation. However, it potentiates the toxic effects of cadmium and nickel on developing neurites, and of the widely used herbicide paraquat possibly by increasing polyamine uptake. Deficiency is associated with spastic paraplegia and Kufor-Rakeb syndrome, in which there is progressive parkinsonism with dementia.
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In 1968, H Reuter and N Seitz published findings that, when Na+ is removed from the medium surrounding a cell, the efflux of Ca2+ is inhibited, and they proposed that there might be a mechanism for exchanging the two ions. In 1969, a group led by PF Baker that was experimenting using squid axons published a finding that proposed that there exists a means of Na+ exit from cells other than the sodium-potassium pump. Digitalis, more commonly known as foxglove, is known to have a large effect on the Na/K ATPase, ultimately causing a more forceful contraction of the heart. The plant contains compounds that inhibit the sodium potassium pump which lowers the sodium electrochemical gradient.
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Moreover, ketolides are effective against macrolide-resistant bacteria, due to their ability to bind at two sites at the bacterial ribosome as well as having a structural modification that makes them poor substrates for efflux-pump mediated resistance.Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor Basic & Clinical Pharmacology, 11e McGraw-Hill 2009 via "accessmedicine.com" Ketolides block protein synthesis by binding to ribosomal subunits and may also inhibit the formation of newly forming ribosomes. According to a recent study comparing the action of the classic macrolides erythromycin and azithromycin with ketolides, which are used to treat serious infections, the more powerful drugs (ketolides) were the more "leaky" in blocking the production of proteins.
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There are at least 3 gene clusters important to DXR biosynthesis: dps genes which specify the enzymes required for the linear polyketide chain synthesis and its first cyclizations, the dnr cluster is responsible for the remaining modifications of the anthracycline structure and the dnm genes involved in the amino sugar, daunosamine, synthesis. Additionally, there is a set of "self resistance" genes to reduce the toxic impact of the anthracycline on the producing organism. One mechanism is a membrane pump that causes efflux of the DXR out of the cell (drr loci). Since these complex molecules are only advantageous under specific conditions, and require a lot of energy to produce, their synthesis is tightly regulated.
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The genomes of several S. thermosulfidooxidans strains have been sequenced, demonstrating a genome size of 3.2-3.9 megabases, with a GC content of 48-49% and a number of bioinformatically defined protein-coding genes ranging from a low of about 3200 to a high of about 3900. All of the sequenced genomes contain large numbers of genes associated with sulfur oxidation; for example, genes encoding sulfur oxygenase reductase (SOR) and heterodisulfide reductase-like enzymes. The genetic basis of the species' iron oxidation capacity is less clear but likely involves a sulfocyanin protein. The genome also contains large numbers of transport proteins, including those specialized for metal ion efflux, and several CRISPR/Cas systems.
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When enough sodium channels are opened, so that the rapid influx of sodium ions is greater than the tonic efflux of potassium ions, then the resting potential becomes progressively less negative, more and more sodium channels are opened, and an action potential is generated. The electrical potential at which this occurs is called the threshold potential. As various drugs and other factors act on the resting potential and bring it closer to the threshold potential, an action potential is more easily and rapidly obtained. Likewise, when the sodium channels are in a state of greater activation, then the influx of sodium ions that allows the membrane to reach threshold potential occurs more readily.
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The resting membrane potential (Vrest) of uterine smooth muscle has been recorded to be between -35 and -80 mV. As with the resting membrane potential of other cell types, it is maintained by a Na+/K+ pump that causes a higher concentration of Na+ ions in the extracellular space than in the intracellular space, and a higher concentration of K+ ions in the intracellular space than in the extracellular space. Subsequently, having K+ channels open to a higher degree than Na+ channels results in an overall efflux of positive ions, resulting in a negative potential. This resting potential undergoes rhythmic oscillations, which have been termed slow waves, and reflect intrinsic activity of slow wave potentials.
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Geologic overpressure in stratigraphic layers is caused by the inability of connate pore fluids to escape as the surrounding mineral matrix compacts under the lithostatic pressure caused by overlying layers. Fluid escape may be impeded by sealing of the compacting rock by surrounding impermeable layers (such as evaporites, chalk and cemented sandstones). Alternatively, the rate of burial of the stratigraphic layer may be so great that the efflux of fluid is not sufficiently rapid to maintain hydrostatic pressure. Common situations where overpressure may occur: in a buried river channel filled with coarse sand that is sealed on all sides by impermeable shales, or when there is an explosion within a confined space.
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Studies have shown that, in certain brain regions, amphetamine and trace amines increase the concentrations of dopamine in the synaptic cleft, thereby heightening the response of the post-synaptic neuron. The various mechanisms by which amphetamine and trace amines affect dopamine concentrations have been studied extensively, and are known to involve both DAT and VMAT2. Amphetamine is similar in structure to dopamine and trace amines; as a consequence, it can enter the presynaptic neuron via as well as by diffusing through the neural membrane directly. Upon entering the presynaptic neuron, amphetamine and trace amines activate TAAR1, which, through protein kinase signaling, induces dopamine efflux, phosphorylation- dependent internalization, and non-competitive reuptake inhibition.
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Zinc transporter proteins (Zrt), or simply zinc transporters, are membrane transport proteins of the solute carrier family which control the membrane transport of zinc and regulate its intracellular and cytoplasmic concentrations. They include two major groups: (1) the zinc transporter (ZnT) or solute carrier 30 (SLC30) family, which controls the efflux of zinc from the cytoplasm out of the cell and from the cytoplasm into vesicles; and (2) the zinc importer, Zrt- and Irt-like protein (ZIP), or solute carrier 39A (SLC39A) family, which controls the influx of zinc into the cytoplasm from outside the cell and from vesicles. At least one zinc transporter, ZIP9, is also a G protein-coupled receptor and membrane androgen receptor.
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Nisin amino acid structure Photo Credit: CacattilaMembers of the microbiota are capable of producing antimicrobial peptides, protecting humans from excessive intestinal inflammation and microbial-associated diseases. Various commensals (primarily Gram-positive bacteria), secrete bacteriocins, peptides which bind to receptors on closely related target cells, forming ion-permeable channels and pores in the cell wall. The resulting efflux of metabolites and cell contents and dissipation of ion gradients causes bacterial cell death. However, bacteriocins can also induce death by translocating into the periplasmic space and cleaving DNA non- specifically (colicin E2), inactivating the ribosome (colicin E3), inhibiting synthesis of peptidoglycan, a major component of the bacterial cell wall (colicin M). Bacteriocins have immense potential to treat human disease.
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Trace amines play significant roles in regulating the quantity of monoamine neurotransmitters in the synaptic cleft of monoamine neurons with . They have well-characterized presynaptic amphetamine-like effects on these monoamine neurons via TAAR1 activation; specifically, by activating TAAR1 in neurons they promote the release and prevent reuptake of monoamine neurotransmitters from the synaptic cleft as well as inhibit neuronal firing. Phenethylamine and amphetamine possess analogous pharmacodynamics in human dopamine neurons, as both compounds induce efflux from vesicular monoamine transporter 2 (VMAT2) and activate TAAR1 with comparable efficacy. Like dopamine, norepinephrine, and serotonin, the trace amines have been implicated in a vast array of human disorders of affect and cognition, such as ADHD, depression and schizophrenia, among others.
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Comparison of the structures suggested a conformational change that involves pivoting of a transmembrane, four-helix bundle (M1, M2, M4, and M5) relative to the M3-M6 helix pair. Although accessibility of transport sites in the x-ray model indicates that it represents an outward-facing state, their model was consistent with an inward-facing state, suggesting that the conformational change is relevant to the alternating access mechanism for transport. They speculated that the dimer may coordinate rearrangement of the transmembrane helices. Involved in metal tolerance/resistance by efflux, most CDF proteins share a two-modular architecture consisting of a transmembrane domain (TMD) and a C-terminal domain (CTD) that protrudes into the cytoplasm.
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The resting membrane potential (Vrest) of uterine smooth muscle has been recorded to be between −35 and −80 mV. As with the resting membrane potential of other cell types, it is maintained by a Na+/K+ pump that causes a higher concentration of Na+ ions in the extracellular space than in the intracellular space, and a higher concentration of K+ ions in the intracellular space than in the extracellular space. Subsequently, having K+ channels open to a higher degree than Na+ channels results in an overall efflux of positive ions, resulting in a negative potential. This resting potential undergoes rhythmic oscillations, which have been termed slow waves, and reflect intrinsic activity of slow wave potentials.
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The other unit consists of an operon, marRAB, encoding (1) the MarR repressor which binds marO and negatively regulates marRAB expression, (2) MarA, a transcriptional activator that activates expression of other genes such as acrAB (encoding the principal E. coli multidrug efflux pump of the RND superfamily (TC #2.A.6.2)) and the mar regulon itself, and (3) MarB, a small protein of 71 amino acyl residues of unknown function. A periplasmic binding protein, MppA, essential for the uptake of the cell wall murein tripeptide, L-alanyl-γ-D-glutamyl-meso- diaminopimelate via the Opp permease, regulates mar regulon expression. Loss of MppA causes overproduction of MarA which activates acrAB, causing pleiotropic drug resistance.
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A different perspective on Alzheimer's is revealed by a mouse study that has found that APP possesses ferroxidase activity similar to ceruloplasmin, facilitating iron export through interaction with ferroportin; it seems that this activity is blocked by zinc trapped by accumulated Aβ in Alzheimer's. It has been shown that a single nucleotide polymorphism in the 5'UTR of APP mRNA can disrupt its translation. The hypothesis that APP has ferroxidase activity in its E2 domain and facilitates export of Fe(II) is possibly incorrect since the proposed ferroxidase site of APP located in the E2 domain does not have ferroxidase activity. As APP does not possess ferroxidase activity within its E2 domain, the mechanism of APP-modulated iron efflux from ferroportin has come under scrutiny.
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In contrast, if both vasa deferentia are obstructed (which may be the result of intended sterilization), a semen analysis will also reveal aspermia/azoospermia, but an almost normal volume of the semen, since the efflux of the seminal vesicles is not hindered. This is because approx. 80% of the volume of the semen is the gel-like fluid originating from the seminal vesicles whereas the fraction from the testicles / epididymis, which contains the spermatozoa accounts for only 5–10% of the volume of the semen. In addition, if an obstruction of the vasa deferentia is the cause for the azoospermia, the concentration of fructose in the semen will also be normal, since the fructose comes primarily from the fluid stored in the seminal vesicles.
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Metal transporter CNNM3 primary structure Regarding the structure, CNNMs contain an N-terminal extracellular domain, a transmembrane domain called DUF21, a large cytosolic region that includes a pair of cystathionine-β-synthase domains, known as CBS-pair, and, furthermore, a putative cyclic nucleotide-binding homology domain, which name is CNBH (Cyclic Nucleotide-Binding Homology). The CBS-pair domain has been extensively characterized, yet little is known about the CNBH domain. In spite of the fact that active member domains can occur as dimers and monomers, the inactive member, CNNM3, can only as a dimer. It exists an inverse correlation between the propensity of the CNBH domains to dimerize and the ability of CNNMs to mediate Mg2+ efflux, which has been proved with analytical ultracentrifugation experiments.
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Work on small RNAs in Dr. Storz's lab revealed that the RNA chaperone Hfq stimulates the pairing of the majority of the small RNAs with mRNA targets and that small RNAs are integral to most regulatory circuits in bacteria. While identifying these small RNAs, her lab discovered that some of these small RNAs encode small proteins that had previously been overlooked because they are not detected in many traditional biochemical assays and the corresponding genes are poorly annotated. Her research group demonstrated that one such small protein, AcrZ, binds to the multidrug efflux pump protein AcrB to affect its ability to export certain classes of antibiotics. The Storz lab currently seeks to identify and to characterize the function of other small proteins from Escherichia coli.
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In a collaboration with Suresh Ambudkar and his group, Stein presented estimates of the turnover numbers for ATP hydrolysis and drug transport by P-glycoprotein, leading them to conclude that more than a single ATP molecule was hydrolyzed for each drug molecule pumped.Ambudkar SV, Cardarelli CO, Pashinsky I, Stein WD. Relation between the turnover number for vinblastine transport and for vinblastine-stimulated ATP hydrolysis by human P-glycoprotein. J Biol Chem 1997; 272: 21160–6. In further collaboration with Litman, and based on detailed kinetic measurements of drug accumulation in cell lines with different levels of the multidrug resistance transporter P-glycoprotein, Stein worked out a simple equation for the “leak-pump” mode of action of the drug efflux pump, P-glycoprotein.
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V. paradoxus has been found in a range of rocky environments including carbonate caves, mine spoil and deep marine sediments, but the role of this organism within these environments is largely unstudied. The species is also tolerant of a large number of heavy metals including cadmium, chromium, cobalt, copper, lead, mercury, nickel, silver, zinc at mM concentrations. Despite this, very little is known about the physiological adaptions V. paradoxus uses to support this tolerance. The sequenced genome of the endophytic strain V. paradoxus S110 provides some clues to the organism's metal tolerance by identifying key molecular machinery in processing metals such as the arsenic reductase complex ArsRBC, metal transporting P1-type ATPases and a chemiosmotic antiporter efflux system similar to CzcCBA of Cupriavidus metallidurans.
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During copulation with the first female, concentrations of dopamine in these male rats showed a significant increase, however, when the same female was presented again, a significant increase in dopamine was not observed. When a novel female was presented, initially, there was a small increase in the levels of dopamine, however, after continued copulation with the novel female, a significant increase in dopamine levels was observed. From these results, they concluded that an increase in mesolimbic dopamine efflux is associated with the appetitive and consummatory stages of sexual behaviour in male rats. Their data also suggest that stimuli associated with a novel female may increase dopamine transmission in a rat that is sexually satiated, and hence have a role in the reinitiation of sexual behaviour.
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In most cases, the release of dopamine occurs through a process called exocytosis which is caused by action potentials, but it can also be caused by the activity of an intracellular trace amine-associated receptor, TAAR1. TAAR1 is a high-affinity receptor for dopamine, trace amines, and certain substituted amphetamines that is located along membranes in the intracellular milieu of the presynaptic cell; activation of the receptor can regulate dopamine signaling by inducing dopamine reuptake inhibition and efflux as well as by inhibiting neuronal firing through a diverse set of mechanisms. Once in the synapse, dopamine binds to and activates dopamine receptors. These can be postsynaptic dopamine receptors, which are located on dendrites (the postsynaptic neuron), or presynaptic autoreceptors (e.g.
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The presumable effect that emodepside interaction with these channels would exert on the neuron would be to activate the channel causing potassium ion efflux, hyper-polarization and subsequent inhibition of excitatory neurotransmitter effect (acetylcholine if acting at the neuromuscular junction), having an inhibitory effect on synaptic transmission, the production of postsynaptic action potentials and ultimately muscle contraction (manifesting itself as paralysis or reduced pharyngeal pumping). Which out of Latrophilin receptors and BK-potassium channels is emodepside's primary site of action remains to be completely deduced. Both LAT-1/LAT-2 and slo-1 mutants (reduction/loss of function) show significant resistance to emodepside with it being conceivable that the presence of both is required for emodepside to induce its full effect.
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It is likely that these two systems act synergistically, with the toxins killing or inhibiting the fungi and exoenzymes degrading the cell wall and digesting the fungus. Examples of necrotrophs include Staphylococcus aureus which feed on Cryptococcus neoformans, Aeromonas caviae which feed on Rhizoctonia solani, Sclerotium rolfsii and Fusarium oxysporum, and some myxobacteria which feed on Cochliobolus miyabeanus and Rhizoctonia solani. Bacteria which manipulate fungi to produce more secretions which they in turn feed off are called extracellular biotrophs; many bacteria feed on fungal secretions, but do not interact directly with the fungi and these are called saprotrophs, rather than biotrophs. Extracellular biotrophs could alter fungal physiology in three ways; they alter their development, the permeability of their membranes (including the efflux of nutrients) and their metabolism.
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This gene encodes the beta subunit of prolyl 4-hydroxylase, a highly abundant multifunctional enzyme that belongs to the protein disulfide isomerase family. When present as a tetramer consisting of two alpha and two beta subunits, this enzyme is involved in hydroxylation of prolyl residues in preprocollagen. This enzyme is also a disulfide isomerase containing two thioredoxin domains that catalyze the formation, breakage and rearrangement of disulfide bonds. Other known functions include its ability to act as a chaperone that inhibits aggregation of misfolded proteins in a concentration-dependent manner, its ability to bind thyroid hormone, its role in both the influx and efflux of S-nitrosothiol- bound nitric oxide, and its function as a subunit of the microsomal triglyceride transfer protein complex.
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Again, because the disease is rarely seen in Western countries, identification of B. pseudomallei in cultures may not actually trigger alarms in physicians unfamiliar with the disease. Routine biochemical methods for identification of bacteria vary widely in their identification of this organism: the API 20NE system accurately identifies B. pseudomallei in 99% of cases, as does the automated Vitek 1 system, but the automated Vitek 2 system only identifies 19% of isolates. The pattern of resistance to antimicrobials is distinctive, and helps to differentiate the organism from P. aeruginosa. The majority of B. pseudomallei isolates are intrinsically resistant to all aminoglycosides (via an efflux pump mechanism), but sensitive to co-amoxiclav: this pattern of resistance almost never occurs in P. aeruginosa and is helpful in identification.
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The intrinsic resistance of most Gram-negative bacteria to linezolid is due to the activity of efflux pumps, which actively "pump" linezolid out of the cell faster than it can accumulate. Gram-positive bacteria usually develop resistance to linezolid as the result of a point mutation known as G2576T, in which a guanine base is replaced with thymine in base pair 2576 of the genes coding for 23S ribosomal RNA. This is the most common mechanism of resistance in staphylococci, and the only one known to date in isolates of E. faecium. Other mechanisms have been identified in Streptococcus pneumoniae (including mutations in an RNA methyltransferase that methylates G2445 of the 23S rRNA and mutations causing increased expression of ABC transporter genes) and in Staphylococcus epidermidis.
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While LDCV kiss-and-run occurred 25% of the time in the presence of forskolin, in the absence of forskolin, LDCV kiss-and-run fusion occurred only 7% of the time. Because forskolin raises cyclic AMP (cAMP) levels, cAMP seemingly plays a very important role in the mechanism in LDCV kiss-and-run fusion in rat pancreatic beta cells. SLV (pore diameter: 0.8 +/- 0.1 nm) and LDCV (pore diameter: 1.4 +/- 0.1 nm) fusion pores during kiss-and- run have been shown to be big enough to allow for efflux of gamma-aminobutyric acid (GABA) and adenosine triphosphate (ATP), but are too small to release insulin in rat pancreatic beta cells. Thus, the kiss-and-run mechanism could be implicated in medical complications involving insulin.
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In animal cells the toll-like receptor TLR4 binds the bacterial PAMP LPS (lipopolysaccharide) and induces K+ efflux through the MaxiK K+ channel, activating signal cascades and release of the pro- inflammatory tumor necrosis factor-α HAK5 works alongside other kinase's to help with the immune response within a cell. The main kinase that works with this transporter is Intergrin- Linked Kinase 1 (ILK1). ILK1 works to increase the amount of HAK5 transporters on the plasma membrane during abiotic stress which increases the influx of K+. ILK1 has also been shown to phosphorylate the N-terminal of HAK5, which contributes to plant growth. The phosphorylation helps to aid in the regulation of the HAK5, as well as other complexes such as CBL1 and CIPK23.
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A number of endogenous TLR4 ligands are elevated in patients with diabetes. Oxidized LDL upregulates TLR4 expression in macrophages and provokes TLR4-dependent inflammation in the arterial wall, further TLR4 activation results in a strong inhibition of cholesterol efflux from macrophages. The hepatic secretory glycoprotein fetuin-A correlates with increased risk of developing T2DM and may promote lipid-induced insulin resistance via TLR4 activation, resulting in production of proinflammatory cytokines. Additionally, mice with deficiencies in TLR4 signaling were protected from insulin resistance caused by high-fat diet and from secondary complications of T2DM such as atherosclerosis. Most SNPs that increase the risk of diabetes reside in noncoding regions of the genes, making the SNP’s mechanism for increasing susceptibility largely unknown.
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As sodium enters the cell, the cell membrane potential becomes more positive, which activates even more sodium channels in the membrane. The sodium influx eventually overtakes the potassium efflux (via the two-pore-domain potassium channels or leak channels, initiating a positive feedback loop (rising phase). At around +40 mV, the voltage-gated sodium channels begin to close (peak phase) and the voltage-gated potassium channels begin to open, moving potassium down its electrochemical gradient and out of the cell (falling phase). The potassium channels exhibit a delayed reaction to the membrane repolarisation, and, even after the resting potential is achieved, some potassium continues to flow out, resulting in an intracellular fluid that is more negative than the resting potential, and during which no action potential can begin (undershoot phase/refractory period).
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Studies have explained that this mobile genetic element has been acquired by different lineages in separate gene transfer events, indicating that there is not a common ancestor of differing MRSA strains. Aminoglycoside antibiotics, such as kanamycin, gentamicin, streptomycin, were once effective against staphylococcal infections until strains evolved mechanisms to inhibit the aminoglycosides' action, which occurs via protonated amine and/or hydroxyl interactions with the ribosomal RNA of the bacterial 30S ribosomal subunit. Three main mechanisms of aminoglycoside resistance mechanisms are currently and widely accepted: aminoglycoside modifying enzymes, ribosomal mutations, and active efflux of the drug out of the bacteria. Aminoglycoside-modifying enzymes inactivate the aminoglycoside by covalently attaching either a phosphate, nucleotide, or acetyl moiety to either the amine or the alcohol key functional group (or both groups) of the antibiotic.
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Cancerous cells exhibit rapid growth and cell division and subsequently have an increased nutritional need. The particularly low-level expression of asparagine synthetase in primary acute lymphoblastic leukemia (ALL) and numerous ALL cell lines, as compared to that of normal cells, makes asparagine depletion an effective method of treatment due to the cells' unusual dependency on circulating serum asparagine as a necessary nutrition for growth. As a result, L-asparaginase is a common chemotherapy drug utilized in the treatment of ALL and may have applications in other asparagine synthetase negative cancers, such as lymphomas, due to its aspariginase activity to deplete serum asparagine. This depletion of serum asparagine leads to a subsequent rapid efflux of cellular asparagine, which is immediately acted upon and destroyed by the L-asparaginase as well.
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Areas in the ocean that are low in oxygen, called oxygen deficient zones (ODZs), are important areas for nitrogen cycling yet only make up about 0.1-0.2% of the total volume of the world ocean. Over one quarter of all nitrogen in the oceans is lost to gaseous nitrogen forms (e.g. N2, N2O) in the ODZs through various nitrogen transformation pathways including denitrification and anammox, however, the rates of nitrogen transformation and type of transformation that is taking place in ODZs remains unclear and subject of much of Ward's research. Ward and her lab developed an isotopic tracer method to measure the rate of N2O reduction in the Eastern Tropical North Pacific Ocean and found that incomplete denitrification in ODZs increases N2O accumulation and eventual efflux to the atmosphere.
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Passive diffusion on a cell membrane. However; in a case of auxins, only the non-dissociated portion of auxin molecules is able to cross the membrane As weak acids, the protonation state of auxins is dictated by the pH of the environment; a strongly acidic environment inhibits the forward reaction (dissociation), whereas an alkaline environment strongly favors it (see Henderson-Hasselbalch equation): The export of auxins from cells is termed auxin efflux and the entry of auxin in to cells is called auxin influx. The first step in polar transport is auxin influx. Auxin enters plant cells by two methods, first by passive diffusion as non-ionized IAA molecule or the protonated form as IAAH across the phospholipid bilayer, or second by active co-transport in the anionic form IAA−.
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Thus, it has been shown for the first time that human activities are causing an increase in oceanic emissions of N2O, and the efflux of this potent greenhouse gas from the Arabian Sea is globally significant, unlike those of CO2 and CH4. Biological productivity in the ocean is sometimes limited by low concentration of iron. This phenomenon, widely prevalent in the Southern Ocean and equatorial Pacific, has been discovered for the first time in the western Arabian Sea, significantly affecting regional biogeochemistry, including the anomalous location of the OMZ. It has been proposed that addition of iron to the HNLC waters could promote biological production causing a drawdown of atmospheric CO2. Consequently, Ocean Iron Fertilization (OIF) has been widely regarded as a potential technique to sequester CO2 from the atmosphere.
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For antibiotic resistance, which represents a widespread problem nowadays, drugs designed to block the mechanisms of bacterial antibiotic resistance are used. For example, bacterial resistance against beta-lactam antibiotics (such as penicillin and cephalosporins) can be circumvented by using antibiotics such as nafcillin that are not susceptible to destruction by certain beta-lactamases (the group of enzymes responsible for breaking down beta-lactams). Beta-lactam bacterial resistance can also be dealt with by administering beta-lactam antibiotics with drugs that block beta-lactamases such as clavulanic acid so that the antibiotics can work without getting destroyed by the bacteria first. Recently, researchers have recognized the need for new drugs that inhibit bacterial efflux pumps, which cause resistance to multiple antibiotics such as beta-lactams, quinolones, chloramphenicol, and trimethoprim by sending molecules of those antibiotics out of the bacterial cell.
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The continued success of this programme and the support of the government caused the petitioner reasonably to expect that it would be continued till the fulfillment of the purpose of the project that is to eradicate malnutrition of under-nourished children. But on the expiry of the contract period, the government discontinued the programme without showing any reason. The High Court Division held that such discontinuance of the programme violating its own policy was in gross violation of the legitimate expectation not only of the petitioner but also of the millions of under-nourished children warranting interference of the court and directed the government to implement its policy decision. Though the government contended that it was not bound to renew the contract and the last contract not being renewed it simply expired by efflux of time without giving any right of action.
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Mechanisms for drug targeting in the brain involve going either "through" or "behind" the BBB. Modalities for drug delivery to the brain in unit doses through the BBB entail its disruption by osmotic means, or biochemically by the use of vasoactive substances, such as bradykinin, or even by localized exposure to high-intensity focused ultrasound (HIFU). Other methods used to get through the BBB may entail the use of endogenous transport systems, including carrier-mediated transporters, such as glucose and amino acid carriers, receptor-mediated transcytosis for insulin or transferrin, and the blocking of active efflux transporters such as p-glycoprotein. Some studies have shown that vectors targeting BBB transporters, such as the transferrin receptor, have been found to remain entrapped in brain endothelial cells of capillaries, instead of being ferried across the BBB into the targeted area.
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In 1968, Lusk described the limitation of bacterial (Escherichia coli) growth on Mg2+-poor media, suggesting that bacteria required Mg2+ and were likely to actively take this ion from the environment. The following year, the same group and another group, Silver, independently described the uptake and efflux of Mg2+ in metabolically active E. coli cells using 28Mg2+. By the end of 1971, two papers had been published describing the interference of Co2+, Ni2+ and Mn2+ on the transport of Mg2+ in E. coli and in Aerobacter aerogenes and Bacillus megaterium. In the last major development before the cloning of the genes encoding the transporters, it was discovered that there was a second Mg2+ uptake system that showed similar affinity and transport kinetics to the first system, but had a different range of sensitivities to interfering cations.
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The poem can be split in two parts, Sections 1-8 and Sections 9-15. During the first part, Whitman describes the open road “as a metaphorical journey characterized by freedom, independence and affirmations of self, time and place” (Kreidler). During this part, Whitman notices how everything is as it should be. He realizes that along the journey one will face a test of wisdom, but, as stated by Kreidler, “Whitman says, ‘not [the wisdom] finally tested in schools’ (92); rather, the wisdom of the soul, revealed through provoking questions, experiences in nature, and experiences along the journey. Further, he avers happiness is the ‘efflux of the soul,’ flowing out, and ‘falls distilled the charm that mocks beauty and attainment’” (143). During part two, Whitman welcomes company along his journey by repeating “the word ‘Allons’ meaning ‘We go’ or ‘Let's go,’” (Kreidler).
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Transcriptomic data allows analysis and comparisons of gene expressions, profiles of secreted molecules, gene functions and products which are important for successfully establishing a symbiotic relationship. Transcriptomic data shows that about 340 genes in XH001 are differentially regulated under coculture conditions. Approximately 70 genes belonging to XH001 genes are up-regulated when XH001 is physically associated with TM7x. These include genes that encode functions related to general stress related responses such as stress related proteins and transcriptional regulators, induced turgor stress-related response, a ribosomal subunit interface protein that binds to machinery of the ribosomes, inhibiting protein biosynthesis, Cys-tRNA-Pro deacylase which prevents addition of amino acids to the tRNA molecule, inhibiting protein translation, TA-encoding systems which include toxin component GNAT family, prevent-host death family protein, YefM TA system and addiction module toxin-RelE family; potassium efflux system KefA homolog, biosynthesis of essential amino acids and transporters.
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Some authors have proposed that a combination of mechanisms can satisfactorily explain the origin of the Athabasca Valles system - namely, the large-scale emplacement of low-viscosity lava flows on top of pre-existing glaciers. Apart from ice interactions, this large-scale low-viscosity volcanic efflux is thought to have formed up to a third of the modern Martian surface and has been analogized to Earth's large igneous provinces (LIPs). Individual periods of volcanic activity constituting the modern Elysium Planitia region are thought to have lasted up to 1 Myr, with the rock in the vicinity of the Athabasca Valles being potentially deposited on a timescale of weeks or months. Given the obliquity of Mars during this part of the Amazonian, it has been hypothesized that glaciers were likely actively accumulating in this region of Elysium Planitia at the same time as this period of volcanism.
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ABCC11 is a gene encoding an apical ATP-driven efflux transporter that has been found to transport a variety of lipophilic anions including cyclic nucleotides, estradiol glucuronide, steroid sulfates such as DHEA-S, and monoanionic bile acids. It is expressed and localized in apocrine glands, including in the axilla, the ceruminous glands in the auditory canal, and in the mammary gland. A single-nucleotide polymorphism (SNP) 538G→A in ABCC11 that leads to a G180R substitution in the encoded protein has been found to result in loss-of-function via affecting N-linked glycosylation and in turn causing proteasomal degradation of the protein. This polymorphism has been found to be responsible for the dry and white earwax phenotype, and is considered to be unique as it has been described as the only human SNP that has been found to determine a visible genetic trait.
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The Kv1.3 K+ channel and the calcium-activated KCa3.1 K+ channel in T cells promote calcium entry into the cytoplasm through CRAC by providing a counterbalancing cation efflux. Blockade of Kv1.3 depolarizes the membrane potential of T cells, suppresses calcium signaling and IL-2 production, but not IL2-receptor expression. Kv1.3 blockers have no effect on activation pathways that are independent of a rise in intracellular calcium (e.g. anti-CD28, IL-2). Expression of the Kv1.3 and KCa3.1 channels varies during T cell activation and differentiation into memory T cells. When naïve T cells and central memory T cells (TCM) are activated they upregulate KCa3.1 expression to ~500 per cell without significant change in Kv1.3 numbers. In contrast, when terminally differentiated effector memory subsets (TEM, TEMRA [T effector memory re-expressing CD45RA]) are activated, they upregulate Kv1.3 to 1500 per cell without changes in KCa3.1. The Kv1.3 channel number increases and the KCa3.1 channel number decreases as T cells are chronically activated.
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The theorem of Torricelli was employed by many succeeding writers, but particularly by Edme Mariotte (1620–1684), whose Traité du mouvement des eaux, published after his death in the year 1686, is founded on a great variety of well-conducted experiments on the motion of fluids, performed at Versailles and Chantilly. In the discussion of some points he committed considerable mistakes. Others he treated very superficially, and in none of his experiments apparently did he attend to the diminution of efflux arising from the contraction of the liquid vein, when the orifice is merely a perforation in a thin plate; but he appears to have been the first who attempted to ascribe the discrepancy between theory and experiment to the retardation of the water's velocity through friction. His contemporary Domenico Guglielmini (1655–1710), who was inspector of the rivers and canals at Bologna, had ascribed this diminution of velocity in rivers to transverse motions arising from inequalities in their bottom.
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" He also stated that efflux disorders have been documented before, and described them as "problems with getting a metal, in this case mercury, out of a cell", citing Wilson's disease as an example thereof. Aposhian also testified, with regard to the concept of a dose- response relationship, that "This is an ancient form of quotation that until recently we taught in medical schools, and in undergraduate school, and in graduate school. We now have to consider the hyper susceptibility of people." According to Arthur Allen, author of the book Vaccine, "On cross examination, Aposhian acknowledged there was no record of any child becoming autistic as a result of mercury exposures prior to the thimerosal theory." In the end, the special master decided that "The reports and advice given to the Cedillos by Dr. [Arthur] Krigsman and some other physicians, advising the Cedillos that there is a causal connection between Michelle’s MMR vaccination and her chronic conditions, have been very wrong.
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The possibility to secure uniformity of depth in a river by lowering the shoals obstructing the channel depends on the nature of the shoals. A soft shoal in the bed of a river is due to deposit from a diminution in velocity of flow, produced by a reduction in fall and by a widening of the channel, or to a loss in concentration of the scour of the main current in passing over from one concave bank to the next on the opposite side. The lowering of such a shoal by dredging merely effects a temporary deepening, for it soon forms again from the causes which produced it. The removal, moreover, of the rocky obstructions at rapids, though increasing the depth and equalizing the flow at these places, produces a lowering of the river above the rapids by facilitating the efflux, which may result in the appearance of fresh shoals at the low stage of the river.
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For this reason, and because they are embedded in the lipid bilayer of the membrane, most membrane proteins are difficult to study and their functions have often been intractable. CEF scientists have done groundbreaking work to overcome some of these challenges and made major contributions to elucidating the structure, mechanisms and regulation of a number of important large complexes, including respiratory complex I , rotary ATPases , supercomplex I1III2IV1 , cytochrome cbb3 oxidase, cytochrome bd oxidase, a sulfide:quinone oxidoreductase, a fungal TOM core complex, a bacterial double-pore K+ uptake system KtrAB, the Na+-independent carnitine/butyrobetaine antiporter CaiT, the betaine/Na+ symporter BetP, the multidrug efflux transporter AcrB and the chaperone and editing TAPBPR–MHC I complex and the human MHC-I peptide-loading complex. Antigenic peptide recognition on TAP was resolved by DNP-enhanced solid-state NMR spectroscopy. The conformational coupling and trans-inhibition in the human antigen transporter ortholog TmrAB was resolved with the aid of dipolar EPR spectroscopy.
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These transmembrane transporters are localised both in the cytoplasmic membrane and in the MM, but in an inverted orientation; this configuration allows them to generate an efflux of Fe2+ ions at the cytoplasmic membrane, and an influx of this same ion at the MM. This step is strictly controlled by a cytochrome-dependent redox system, which is not yet fully explained and appears to be species-specific. During the final stage of the process, the magnetite crystal nucleation is by action of transmembrane proteins with acidic and basic domains. One of these proteins, called Mms6, has also been employed for the artificial synthesis of magnetite, where its presence allows the production of crystals homogeneous in shape and size. It is likely that many other proteins associated with the MM could be involved in other roles, such as generation of supersaturated concentrations of iron, maintenance of reducing conditions, oxidisation of iron, and partial reduction and dehydration of hydrated iron compounds.
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On 21 November 2016, at around 6pm, a powerful southerly change occurred in Melbourne, which resulted in the death of 10 people, who were asthmatic and succumbed to respiratory failure.Melbourne thunderstorm asthma victims left waiting for ambulances which had not been despatched by Karen Percy (ABC News) Thousands of others across the city experienced allergic reactions and asthma-like symptoms triggered by the storm.Coronial investigation uncovers tenth thunderstorm asthma death by Aisha Dow (The Age) This was due to a stark southerly wind (60 km/hour) that distributed ryegrass pollen into the moist air, rupturing them into very fine specks, small enough particles to enter people's lungs, as they were sucked up into the warm updraft of air forming the storm cells, before they returned to earth in the storm's cool down-draft, spreading across the land in the storm's efflux area.Thunderstorm asthma deaths: ambulance dispatch 'unlikely' factor – coroner by Melissa Davey (The Guardian) Hospitals and medical centres in the city had to arduously manage 8,500 emergency calls in the space of just five hours, and the hospitalisation of 1400 people.
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Using new MGS data, the authors affirmed the initial Viking-era hypotheses that both water and lava features shaping the Athabasca Valles may have erupted at different times from the Cerberus Fossae fissures, although diagnostic morphological signs had since been overprinted by later geological events in the fossae. The study also explored potential sources of the water thought to have formed the Athabasca Valles, reasoning that an extremely deep reservoir of water with some protective layer was necessary to concentrate efflux of fluid matter through the narrow Cerberus Fossae system and to delay the outflow of water to such a late part of the Amazonian. Aquifer recharge by precipitation, long-distance water transport in the regolith from the highlands, local burial of glacial ice under volcanics, and atmospheric recharge via condensation were all suggested as possible but uncertain explanations. A review was published concurrently by Devon Burr, Jennifer Grier, Alfred McEwen and Laszlo Keszthelyi (of the University of Arizona and Arizona State University), also using recently published MGS data (MOC and MOLA).
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Crystallographic structural studies of a potassium channel have shown that, when a potential difference is introduced over the membrane, the associated electric field induces a conformational change in the potassium channel. The conformational change distorts the shape of the channel proteins sufficiently such that the cavity, or channel, opens to allow influx or efflux to occur across the membrane. This movement of ions down their concentration gradients subsequently generates an electric current sufficient to depolarize the cell membrane. Voltage-gated sodium channels and calcium channels are made up of a single polypeptide with four homologous domains. Each domain contains 6 membrane spanning alpha helices. One of these helices, S4, is the voltage sensing helix. The S4 segment contains many positive charges such that a high positive charge outside the cell repels the helix, keeping the channel in its closed state. In general, the voltage sensing portion of the ion channel is responsible for the detection of changes in transmembrane potential that trigger the opening or closing of the channel. The S1-4 alpha helices are generally thought to serve this role.
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Private jetties near the mouth of the alt= A small tidal rise spreading tidal water over a large expanse of lagoon or inland backwater causes the influx and efflux of the tide to maintain a deep channel through a narrows no longer confined by a bank on each side, becomes dispersed, and owing to the reduction of its scouring force, is no longer able at a moderate distance from the shore effectually to resist the action of tending to form a continuous beach in front of the outlet. Hence a bar is produced that diminishes the available depth in the approach channel. By carrying out a solid jetty over the bar, however on each side of the outlet, the tidal currents are concentrated in the channel across the bar, and lower it by scour. Thus the available depth of the approach channels to Venice through the Malamocco and Lido outlets from the Venetian Lagoon have been deepened several feet (metres) over their bars by jetties of rubble, carried out across the foreshore into deep water on both sides of the channel.
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LA is able to scavenge reactive oxygen and reactive nitrogen species in a biochemical assay due to long incubation times, but there is little evidence this occurs within a cell or that radical scavenging contributes to the primary mechanisms of action of LA. The relatively good scavenging activity of LA toward hypochlorous acid (a bactericidal produced by neutrophils that may produce inflammation and tissue damage) is due to the strained conformation of the 5-membered dithiolane ring, which is lost upon reduction to DHLA. In cells, LA is reduced to dihydrolipoic acid, which is generally regarded as the more bioactive form of LA and the form responsible for most of the antioxidant effects and for lowering the redox activities of unbound iron and copper. This theory has been challenged due to the high level of reactivity of the two free sulfhydryls, low intracellular concentrations of DHLA as well as the rapid methylation of one or both sulfhydryls, rapid side-chain oxidation to shorter metabolites and rapid efflux from the cell. Although both DHLA and LA have been found inside cells after administration, most intracellular DHLA probably exists as mixed disulfides with various cysteine residues from cytosolic and mitochondrial proteins.
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These primary metabolites are thought to be primarily released through the root tip when the rhizosphere is negatively affected by stressors such as being nutrient poor. This environmental sense of surroundings allows the plant to dictate when these metabolites should be released. The mechanism described for this process is illustrated by facilitated diffusion from the root tip, this process requires the possible adjustment of the source sink conserves and this creates a pressure driven mechanism through the phloem. Traveling through the simplistic pathway is the most common method as they can travel freely however while nearing their journey, they have to pass through a plasma membrane and to do this they need a transmembrane protein to complete the trip. “The phloem unloads the primary metabolites through the plasmodesmata using both facilitated diffusion and pressure flow mechanics to push release at the root tip”. Another possible mechanism of release of exudates would be the plants ability to control “efflux of primary metabolites is controlled through distinct channels and carriers which in turn allow down regulation in response to gene expression and or post translational modifications” examples of such transporters are GDU, SWEET, and CAT transporters.
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"Velar" clicks in these languages have only a single release burst, that of the forward release, and the release of the rear articulation isn't audible. However, in other languages all clicks are velar, and a few languages, such as Taa, have a true velar–uvular distinction that depends on the place rather than the timing of rear articulation and is audible in the quality of the vowel. Regardless, in most of the literature the stated place of the click is the anterior articulation (called the release or influx), whereas the manner is ascribed to the posterior articulation (called the accompaniment or efflux). The anterior articulation defines the click type and is written with the IPA letter for the click (dental , alveolar , etc.), whereas the traditional term 'accompaniment' conflates the categories of manner (nasal, affricated), phonation (voiced, aspirated, breathy voiced, glottalised), as well as any change in the airstream with the release of the posterior articulation (pulmonic, ejective), all of which are transcribed with additional letters or diacritics, as in the nasal alveolar click, or or—to take an extreme example—the voiced (uvular) ejective alveolar click, .
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The cyclic nucleotides (cGMP and cAMP) produced by these cyclases activate Protein Kinase G and Protein Kinase A and phosphorylate a number of proteins. The phosphorylation events lead to a decrease in intracellular calcium (inhibit L type Calcium channels, inhibits IP3 receptor channels, stimulates sarcoplasmic reticulum Calcium pump ATPase), a decrease in the 20kd myosin light chain phosphorylation by altering calcium sensitization and increasing myosin light chain phosphatase activity, a stimulation of calcium sensitive potassium channels which hyperpolarize the cell, and the phosphorylation of amino acid residue serine 16 on the small heat shock protein (hsp20)by Protein Kinases A and G. The phosphorylation of hsp20 appears to alter actin and focal adhesion dynamics and actin-myosin interaction, and recent evidence indicates that hsp20 binding to 14-3-3 protein is involved in this process. An alternative hypothesis is that phosphorylated Hsp20 may also alter the affinity of phosphorylated myosin with actin and inhibit contractility by interfering with crossbridge formation. The endothelium derived hyperpolarizing factor stimulates calcium sensitive potassium channels and/or ATP sensitive potassium channels and stimulate potassium efflux which hyperpolarizes the cell and produces relaxation.
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