MicroRNAs influence protein activities throughout the body, and they are easily measured in biofluids, including blood, cerebrospinal fluid and saliva, according to the authors.
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An information-theoretic framework for biomarker discovery, integrating biofluid and tissue information, has been introduced; this approach takes advantage of functional synergy between certain biofluids and tissues, with the potential for clinically significant findings (not possible if tissues and biofluids were considered separately). By conceptualizing tissue biofluids as information channels, significant biofluid proxies were identified and then used for guided development of clinical diagnostics. Candidate biomarkers were then predicted, based on information-transfer criteria across the tissue-biofluid channels. Significant biofluid-tissue relationships can be used to prioritize the clinical validation of biomarkers.
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Biofluids are more readily accessible, unlike more invasive or unfeasible techniques (such as tissue biopsy). Biofluids contain proteins from tissues and serve as effective hormonal communicators. The tissue acts as a transmitter of information, and the biofluid (sampled by physician) acts as a receiver. The informativeness of the biofluid relies on the fidelity of the channel.
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The proteomic networks contain many biomarkers that are proxies for development and illustrate the potential clinical application of this technology as a way to monitor normal and abnormal fetal development. An information theoretic framework has also been introduced for biomarker discovery, integrating biofluid and tissue information. This new approach takes advantage of functional synergy between certain biofluids and tissues with the potential for clinically significant findings not possible if tissues and biofluids were considered individually.
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Proximity in these abstract spaces signifies a low level of distortion across the information channel (and, hence, high performance by the biofluid). However, current approaches to biomarker prediction have analyzed tissues and biofluids separately.
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Because an organism's metabolome is largely defined by its genome, different species will have different metabolomes. Indeed, the fact that the metabolome of a tomato is different than the metabolome of an apple is the reason why these two fruits taste so different. Furthermore, different tissues, different organs and biofluids associated with those organs and tissues can also have distinctly different metabolomes. The fact that different organisms and different tissues/biofluids have such different metabolomes has led to the development of a number of organism-specific and biofluid-specific metabolome databases.
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In this case, the inverse Fahraeus–Lindquist effect occurs and the wall shear stress increases. An example of a gaseous biofluids problem is that of human respiration. Recently, respiratory systems in insects have been studied for bioinspiration for designing improved microfluidic devices.
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It is a normal metabolite found in human biofluids. Phosphoserine has three potential coordination sites (carboxyl, amine and phosphate group) Determination of the mode of coordination between phosphorylated ligands and metal ions occurring in an organism is a first step to explain the function of the phosphoserine in bioinorganic processes.
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Sibutramine and its two active N-demethylated metabolites may be measured in biofluids by liquid chromatography-mass spectrometry. Plasma levels of these three species are usually in the 1–10 μg/L range in persons undergoing therapy with the drug. The parent compound and norsibutramine are often not detectable in urine, but dinorsibutramine is generally present at concentrations of >200 μg/L.Jain DS, Subbaiah G, Sanyal M, et al.
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MALDI is also used however, the application of a MALDI matrix can add significant background at <1000 Da that complicates analysis of the low-mass range (i.e., metabolites). In addition, the size of the resulting matrix crystals limits the spatial resolution that can be achieved in tissue imaging. Because of these limitations, several other matrix-free desorption/ionization approaches have been applied to the analysis of biofluids and tissues.
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For instance, blood circulation in the cardiovascular system is maintained to some extent even when the heart's valves fail. Meanwhile, the embryonic vertebrate heart begins pumping blood long before the development of discernible chambers and valves. In microfluidics, valveless impedance pumps have been fabricated, and are expected to be particularly suitable for handling sensitive biofluids. Ink jet printers operating on the piezoelectric transducer principle also use valveless pumping.
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Biomarkers for a number of diseases have recently emerged, including prostate specific antigen (PSA) for prostate cancer and C-reactive protein (CRP) for heart disease. The epigenetic clock which measures the age of cells/tissues/organs based on DNA methylation levels is arguably the most accurate genomic biomarker. Using biomarkers from easily assessable biofluids (e.g. blood and urine) is beneficial in evaluating the state of harder-to- reach tissues and organs.
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Nitrate reductase activity can be used as a biochemical tool for predicting grain yield and grain protein production. Nitrate reductase can be used to test nitrate concentrations in biofluids. Nitrate reductase promotes amino acid production in tea leaves. Under south Indian conditions, it is reported that tea plants sprayed with various micronutrients (like Zn, Mn and B) along with Mo enhanced the amino acid content of tea shoots and also the crop yield.
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MetaboMiner is a tool which can be used to automatically or semi-automatically identify metabolites in complex biofluids from 2D-NMR spectra. MetaboMiner is able to handle both 1H-1H total correlation spectroscopy (TOCSY) and 1H-13C heteronuclear single quantum correlation (HSQC) data. It identifies compounds by comparing 2D spectral patterns in the NMR spectrum of the biofluid mixture with specially constructed libraries containing reference spectra of approximately 500 pure compounds. MetaboMiner protocol is available via MetaboMiner website.
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The ability to analyze the composition of a mixture on the nano scale makes the use of SERS substrates beneficial for environmental analysis, pharmaceuticals, material sciences, art and archeological research, forensic science, drug and explosives detection, food quality analysis, and single algal cell detection. SERS combined with plasmonic sensing can be used for high-sensitivity and quantitative analysis of small molecules in human biofluids, quantitative detection of biomolecular interaction, and to study redox processes at the single molecule level.
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Samples of antibody microarray creations and detections. An antibody microarray (also known as antibody array) is a specific form of protein microarray. In this technology, a collection of capture antibodies are spotted and fixed on a solid surface such as glass, plastic, membrane, or silicon chip, and the interaction between the antibody and its target antigen is detected. Antibody microarrays are often used for detecting protein expression from various biofluids including serum, plasma and cell or tissue lysates.
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Sources of noise which decrease fidelity include the addition of proteins derived from other tissues (or from the biofluid itself); proteins may also be lost through glomerular filtration. These factors can significantly influence the protein composition of a biofluid. In addition, simply looking at protein overlap would miss information transmission occurring through classes of proteins and protein-protein interactions. Instead, the proteins' projection onto functional, drug, and disease spaces allow measurement of the functional distance between tissue and biofluids.
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A nanoscale enzymatic biofuel cell for self-powered nanodevices have been developed that uses glucose from biofluids including human blood and watermelons. One limitation to this innovation is the fact that electrical interference or leakage or overheating from power consumption is possible. The wiring of the structure is extremely difficult because they must be positioned precisely in the nervous system. The structures that will provide the interface must also be compatible with the body's immune system.
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Carbide- derived carbons with a mesoporous structure remove large molecules from biofluids. As other carbons, CDCs possess good biocompatibility. CDCs have been demonstrated to remove cytokines such as TNF-alpha, IL-6, and IL-1beta from blood plasma. These are the most common receptor-binding agents released into the body during a bacterial infection that cause the primary inflammatory response during the attack and increase the potential lethality of sepsis, making their removal a very important concern.
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The mechanical analysis of biomaterials and biofluids is usually carried forth with the concepts of continuum mechanics. This assumption breaks down when the length scales of interest approach the order of the micro structural details of the material. One of the most remarkable characteristic of biomaterials is their hierarchical structure. In other words, the mechanical characteristics of these materials rely on physical phenomena occurring in multiple levels, from the molecular all the way up to the tissue and organ levels.
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Hannah- Brown remained at King's College London as an Engineering and Physical Sciences Research Council (EPSRC) funded postdoctoral researcher. She became a lecturer in the Department of Pharmacy in 2000. She won the Desty Memorial Prize for Contribution to Separation Science in 2000. She developed instrumentation to enable detection of trace components in biofluids supported by Research Councils UK. In 2006 Hanna-Brown was appointed as Separation Science Lead at Pfizer UK, and made head of the Analytical Team in 2008.
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Questions that can be answered by biomarkers A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. Ideally, such biomarkers can be assayed in non-invasively collected biofluids like blood or serum.
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The concentration of calcium phosphate is higher in milk than in serum, but it rarely forms deposits of insoluble phosphates. Unfolded phosphopeptides are believed to sequester ACP nanoclusters, and form stable complexes in other biofluids such as urine and blood serum, thus preventing deposition of insoluble calcium phosphates and calcification of soft tissue. In the laboratory, stored samples of formulations of artificial blood, serum, urine and milk (which approximate the pH of the naturally occurring fluid) deposit insoluble phosphates. The addition of suitable phosphopeptides prevents precipitation.
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Furthermore, heroin contains codeine (or acetyl codeine) as an impurity and its use will result in excretion of small amounts of codeine. Poppy seed foods represent yet another source of low levels of codeine in one's biofluids. Blood or plasma codeine concentrations are typically in the 50–300 µg/L range in persons taking the drug therapeutically, 700–7000 µg/L in chronic users and 1000–10,000 µg/L in cases of acute fatal over dosage. Codeine is produced in the human body along the same biosynthetic pathway as morphine.
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Surface-based mass analysis has seen a resurgence in the past decade, with new MS technologies focused on increasing sensitivity, minimizing background, and reducing sample preparation. The ability to analyze metabolites directly from biofluids and tissues continues to challenge current MS technology, largely because of the limits imposed by the complexity of these samples, which contain thousands to tens of thousands of metabolites. Among the technologies being developed to address this challenge is Nanostructure-Initiator MS (NIMS), a desorption/ ionization approach that does not require the application of matrix and thereby facilitates small-molecule (i.e., metabolite) identification.
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There is an increasing trend of using ICP-MS as a tool in speciation analysis, which normally involves a front end chromatograph separation and an elemental selective detector, such as AAS and ICP-MS. For example, ICP-MS may be combined with size exclusion chromatography and quantitative preparative native continuous polyacrylamide gel electrophoresis (QPNC-PAGE) for identifying and quantifying native metal cofactor containing proteins in biofluids. Also the phosphorylation status of proteins can be analyzed. In 2007, a new type of protein tagging reagents called metal-coded affinity tags (MeCAT) were introduced to label proteins quantitatively with metals, especially lanthanides.
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LAESI is a novel ionization source for mass spectrometry (MS) that has been used to perform MS imaging of plants, tissues, cell pellets, and even single cells. In addition, LAESI has been used to analyze historic documents and untreated biofluids such as urine and blood. The technique of LAESI is performed at atmospheric pressure and therefore overcomes many of the obstacles of traditional MS techniques, including extensive and invasive sample preparation steps and the use of high vacuum. Because molecules and aerosols are ionized by interacting with an electrospray plume, LAESI's ionization mechanism is similar to SESI and EESI techniques.
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LAESI can be used to perform MS imaging experiments of diverse tissue samples, not only in three dimensions but also with respect to time. Similarly, LAESI can also be used for process monitoring applications because each individual analysis requires less than 2 seconds to perform. Because of the speed of a LAESI analysis, the technique is amenable to rapid, sensitive, and direct analysis of aqueous samples in 96- and 384-well microplates. These analyses can also be performed on liquid samples, such as biofluids, containing peptides, proteins, metabolites, and other biomarkers for clinical, diagnostic, and discovery workflows.
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Clonazepam and 7-aminoclonazepam may be quantified in plasma, serum, or whole blood in order to monitor compliance in those receiving the drug therapeutically. Results from such tests can be used to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. Both the parent drug and 7-aminoclonazepam are unstable in biofluids, and therefore specimens should be preserved with sodium fluoride, stored at the lowest possible temperature and analyzed quickly to minimize losses.R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 335-337.
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The MSEA web server is a freely available web server for performing metabolite set enrichment analysis on human or mammalian metabolomics data. The required input is either a list of compound names or compound names and concentrations. The output is a set of graphs and tables with embedded hyperlinks to the pertinent pathway images and descriptors. The Metabolite Set Enrichment Analysis offered by the web server is based on a curated library of more 5000 predefined metabolite sets covering various human metabolic pathways (nearly 100), hundreds of human disease states (in 3 different biofluids), human biofluid and tissue locations as well as human SNP-metabolite associations (4500 different SNP associations).
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Graphic depicting the human skin microbiota, with relative prevalences of various classes of bacteria The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, placenta, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, biliary tract, and gastrointestinal tract. Types of human microbiota include bacteria, archaea, fungi, protists and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.
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Secondary ion mass spectrometry (SIMS) was one of the first matrix-free desorption/ionization approaches used to analyze metabolites from biological samples. SIMS uses a high-energy primary ion beam to desorb and generate secondary ions from a surface. The primary advantage of SIMS is its high spatial resolution (as small as 50 nm), a powerful characteristic for tissue imaging with MS. However, SIMS has yet to be readily applied to the analysis of biofluids and tissues because of its limited sensitivity at >500 Da and analyte fragmentation generated by the high-energy primary ion beam. Desorption electrospray ionization (DESI) is a matrix-free technique for analyzing biological samples that uses a charged solvent spray to desorb ions from a surface.
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Some of the better known metabolome databases include the Human Metabolome Database or HMDB, the Yeast Metabolome Database or YMDB, the E. coli Metabolome Database or ECMDB, the Arabidopsis metabolome database or AraCyc as well as the Urine Metabolome Database, the Cerebrospinal Fluid (CSF) Metabolome Database and the Serum Metabolome Database. The latter three databases are specific to human biofluids. A number of very popular general metabolite databases also exist including KEGG, MetaboLights, the Golm Metabolome Database, MetaCyc, LipidMaps and Metlin. Metabolome databases can be distinguished from metabolite databases in that metabolite databases contain lightly annotated or synoptic metabolite data from multiple organisms while metabolome databases contain richly detailed and heavily referenced chemical, pathway, spectral and metabolite concentration data for specific organisms.
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LSD may be quantified in urine as part of a drug abuse testing program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims or in whole blood to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. Both the parent drug and its major metabolite are unstable in biofluids when exposed to light, heat or alkaline conditions and therefore specimens are protected from light, stored at the lowest possible temperature and analyzed quickly to minimize losses.R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 12th edition, Biomedical Publications, Foster City, CA, 2020, pp. 1197-1199. The apparent plasma half life of LSD is considered to be around 5.1 hours with peak plasma concentrations occurring 3 hours after administration.
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Proteomics research received a boost in 2008 when Canada's most powerful research computer an IBM supercomputer was installed in Toronto. The $20 million machine, about the size of an SUV, can make 12.5 trillion computations per second and will be used for proteomics research by the Ontario Cancer Institute, the Princess Margaret Hospital (specializing in cancer) and the University Health Network. A new field, metabolomics, has generated much recent interest. The logical next step after genomics, which studies the plan for protein construction and proteomics, which studies the manufacture of the proteins themselves from that plan, metabolomics studies the metabolic molecules produced by those proteins in an organism. After receiving a $7.5 million grant from Genome Canada and Genome Alberta, the University of Alberta in Edmonton began the Human Metabolome Project in 2005 with the goal of identifying, quantifying and cataloguing all metabolites in human tissue and biofluids.
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