The researchers' paper was published in the journal Nature, and named the subtypes as: - Squamous - Pancreatic Progenitor - Immunogenic - Aberrantly Differentiated Endocrine eXocrine, or ADEX.
|
|
The aberrantly uncompetitive US ISP market leads to situations where someone like Comcast or Spectrum can effectively dictate whatever terms it likes to its customers.
|
|
Microsoft's Surface Book suffered from a number of power management problems relating to Skylake, and other PC manufacturers also had to issue an aberrantly high number of firmware and driver updates for their Skylake machines.
|
|
Three years later he was nearly seven feet tall, with physical advantages that allowed him to control the paint, and enough skill to step out and unleash a potent jumper that started on his right and aberrantly followed through across his body (a form that was nicknamed the "Seagoville Shot" in college).
|
|
He noted that Kansas has an unlikely 6-1 record in one-possession and overtime games this season, further explaining its aberrantly high R.P.I. By contrast, NET factors game location into its Team Value Index, and the N.C.A.A. also sorts wins into quadrants based on whether they came at home, on the road or at a neutral court.
|
|
Cells may aberrantly express B-cell marker CD20 and the NK marker CD56. Monoblasts may be positive for CD34.
|
|
CD7 can be aberrantly expressed in refractory anaemia with excess blasts (RAEB) and may confer a worse prognosis. Also, a lack of CD7 expression could insinuate mycosis fungoides (MF) or Sezary syndrome (SS).
|
|
Glycyl-tRNA synthetase has been shown to interact with EEF1D. Mutant forms of the protein associated with peripheral nerve disease have been shown to aberrantly bind to the transmembrane receptor proteins neuropilin 1 and Trk receptors A-C.
|
|
OATP1B3 has also been identified as a transporter aberrantly expressed in prostate cancer and implicated in prostate cancer progression. Increasing mRNA expression of OATP1B3 was also correlated to prostate cancer Gleason score. In addition, lower expression of OATP1B3 mRNA was also detected in testicular cancer.
|
|
Studies into human breast tissue lines and primary breast tumors have observed that the gene FOXJ1 are aberrantly hypermethylated in primary tumors. This hypermethylation serves to silence production of the FOXJ1 protein and has been proposed as a potentially important event in tumor formation.
|
|
Apple wireless Mighty Mouse An optional Bluetooth-based cordless version of the Apple Mouse in white, released in 2003 was Apple's first cordless mouse. Combined with internal Bluetooth interfaces in new Macs, this bypassed their wired relatives' aberrantly short cords to once again make Apple's mouses usable for left-handed laptop owners.
|
|
The p25 form accumulates in the brain neurons of patients with Alzheimer's disease. This accumulation correlates with an increase in CDK5 kinase activity, and may lead to aberrantly phosphorylated forms of the microtubule-associated protein tau, which contributes to Alzheimer's disease. In melanocytic cells CDK5R1 gene expression may be regulated by MITF.
|
|
Similarly to the related cytosine modifications 5-Methylcytosine (5mC) and 5hmC, 5fC is broadly distributed across the mammalian genome, although it is much more rarely occurring. The specific concentration values vary significantly depending on the cell type. 5fC can be aberrantly expressed in distinct sets of tissue that can indicate different tumor onsets and canceration.
|
|
Neutrophil elastase is an important protease enzyme that when expressed aberrantly can cause emphysema or emphysematous changes. This involves breakdown of the lung structure and increased airspaces. Mutations of the ELANE gene cause cyclic and severe congenital neutropenia, which is a failure of neutrophils to mature. In 2019 study was confirmed that ELANE deletion does not cause neutropenia.
|
|
Once the compression has relieved, regeneration of axons from the lesion site begins. This time though, only 50% of the set of axons that innervate the orbicularis oris successfully reinnervate the original site. The other half aberrantly branched off and innervated the orbicularis oculi(eye muscle). Thus, when the patient purses their lips, the ipsilateral eye will squint.
|
|
Ashman beats are described as wide complex QRS complexes that follow a short R-R interval preceded by a long R-R interval. This short QRS complex typically has a right bundle branch block morphology and represents an aberrantly conducted complex that originates above the AV node, rather than a complex that originates in either the right or left ventricle.
|
|
DNA methylation involves the addition of a methyl group to the carbon-5 position of the cytosine ring in the CpG dinucleotide and converting it to methylcytosine. This process is catalyzed by DNA methyltransferase. In numerous cancers, the CpG islands of selected genes are aberrantly methylated (hypermethylated) which results in transcriptional repression. This may be an alternate mechanism of gene inactivation.
|
|
However, cyclin A2/CDK complexes do not function strictly as activators of cyclin B1/CDK1 in G2, as CDK2 has been shown to be required for activation of the p53-independent G2 checkpoint activity, perhaps through a stabilizing phosphorylation on Cdc6. CDK2-/- cells also have aberrantly high levels of Cdc25A. Cyclin A2/CDK1 has also been shown to mediate proteasomal destruction of Cdc25B.
|
|
Both types of contact inhibition are well-known properties of normal cells and contribute to the regulation of proper tissue growth, differentiation, and development. It is worth noting that both types of regulation are normally negated and overcome during organogenesis during embryonic development and tissue and wound healing. However, contact inhibition of locomotion and proliferation are both aberrantly absent in cancer cells, and the absence of this regulation contributes to tumorigenesis.
|
|
The activity of scramblase does not require energy, meaning that there is no contribution of adenosine triphosphate in the process. Scramblases are proline-rich proteins, possessing many cysteinyl sulfhydryl groups that are prone to modifications. Oxidation, nitrosylation, and blockage of these sulfhydryl groups produce an enhanced scramblase activity. Patients with sickle cell disease exhibit a fraction of erythrocytes with an aberrantly enhanced exposure of phosphotidyl serine on their surface.
|
|
Unchecked or overactive TFH cell immune responses have the potential to mount unwarranted germinal centers, composed of aberrantly mutated B cells that can drive antibody-mediated autoimmune diseases. Elevated levels of TFH-like cells can be detected in the blood of a subset of human patients with systemic lupus erythematosus (SLE) and Sjögren syndrome. However, scientific evidence suggesting TFH cells can definitively cause autoimmunity in humans remains incomplete.
|
|
The classic example of targeted development is imatinib mesylate (Gleevec), a small molecule which inhibits a signaling molecule kinase. The genetic abnormality causing chronic myelogenous leukemia (CML) has been known for a long time to be a chromosomal translocation creating an abnormal fusion protein, kinase BCR-ABL, which signals aberrantly, leading to uncontrolled proliferation of the leukemia cells. Imatinib precisely inhibits this kinase. Unlike so many other anti-cancer agents, this pharmaceutical was no accident.
|
|
ALS patients and mouse models show general histone hypoacetylation that can ultimately trigger apoptosis of cells. In experiments with mice, HDAC inhibitors counteract this hypoacetylation, reactivate aberrantly down-regulated genes, and counteract apoptosis initiation. Furthermore, HDAC inhibitors are known to prevent SOD1 protein aggregates in vitro. ;Sodium phenylbutyrate: Sodium phenylbutyrate treatment in a SOD1 mouse model of ALS showed improved motor performance and coordination, decreased neural atrophy and neural loss, and increased weight gain.
|
|
Aromatase and 17beta-hydroxysteroid dehydrogenase are aberrantly expressed in fibroids, indicating that fibroids can convert circulating androstenedione into estradiol. Similar mechanism of action has been elucidated in endometriosis and other endometrial diseases. Aromatase inhibitors are currently considered for treatment, at certain doses they would completely inhibit estrogen production in the fibroid while not largely affecting ovarian production of estrogen (and thus systemic levels of it). Aromatase overexpression is particularly pronounced in African-American women.
|
|
AZD0530 is an inhibitor of Src and Abl family kinases1. It has been developed as treatment for malignancies because these kinases play a role in tumor invasion and proliferation. However, the Src family kinases (SFKs) are highly expressed in brain and have major effects on synaptic plasticity2. Moreover, the investigators have recently shown that a specific SFK, namely Fyn, is aberrantly activated by specific conformations of the Amyloid Beta (Aß) peptide from Alzheimer's disease (AD).
|
|
Mitral valve prolapse can result in mitral regurgitation, shown here, in which blood abnormally flows from the left ventricle back into the left atrium. Mitral valve prolapse is frequently associated with mild mitral regurgitation, where blood aberrantly flows from the left ventricle into the left atrium during systole. In the United States, MVP is the most common cause of severe, non-ischemic mitral regurgitation. This is occasionally due to rupture of the chordae tendineae that support the mitral valve.
|
|
Variants in this gene have been associated with Type 1 diabetes, Graves' disease, Hashimoto's thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, primary biliary cirrhosis and other autoimmune diseases. Polymorphisms of the CTLA-4 gene are associated with autoimmune diseases such as rheumatoid arthritis, autoimmune thyroid disease and multiple sclerosis, though this association is often weak. In systemic lupus erythematosus (SLE), the splice variant sCTLA-4 is found to be aberrantly produced and found in the serum of patients with active SLE.
|
|
This receptor is a glycosylated, 7-transmembrane G-protein coupled receptor that activates the phospholipase C signaling pathway. The receptor is aberrantly expressed in numerous cancers such as those of the lung, colon, and prostate. An individual with autism and multiple exostoses was found to have a balanced translocation between chromosome 8 and a chromosome X breakpoint located within the gastrin-releasing peptide receptor gene. The transcription factor CREB is a regulator of human GRP-R expression in colon cancer.
|
|
Normal cells will display the normal protein antigen on their MHC molecules, whereas cancer cells will display the mutant version. Some viral proteins are implicated in forming cancer (oncogenesis), and some viral antigens are also cancer antigens. Cancer-testis antigens are antigens expressed primarily in the germ cells of the testes, but also in fetal ovaries and the trophoblast. Some cancer cells aberrantly express these proteins and therefore present these antigens, allowing attack by T-cells specific to these antigens.
|
|
With Kathryn Ferguson and others, he also played an important role in understanding the structure and function of the Pleckstrin homology domain in phosphoinositide signalling and elsewhere. Lemmon has made important contributions to the discovery of both normal and pathological activation mechanisms of growth factor receptors and the signalling networks that they engage within cells. He is also committed to exploiting this understanding clinically. These receptors and their downstream effectors are activated aberrantly in numerous cancers, and are important targets of cancer drugs.
|
|
Expression of egfl7 is endothelial cell- specific in physiological conditions, however it is aberrantly expressed by tumour cells in human cancers. In colorectal cancer, high levels of egfl7 correspond to tumours with higher pathologic stages and to the presence of lymph node metastases. Egfl7 is also over-expressed by tumour cells in human hepatocellular carcinoma and overexpression is significantly higher in tumours with multiple nodules, without capsules and with vein invasion. Levels of egfl7 are thus correlated with markers of metastasis and with poor prognosis.
|
|
Gene conversion occurs when the intact SBDS gene and its pseudogene copy aberrantly recombine at meiosis, leading to an incorporation of pseudogene-like sequences into the otherwise functional copy of the SBDS gene, thereby inactivating it. Two gene conversion mutations predominate in SDS patients. One is a splice site mutation affecting the 5' splice site of intron two, while the second is an exon two nonsense mutation. The marked absence of patients homozygous for the otherwise common nonsense mutation suggested that the SBDS gene is essential.
|
|
In normal cellular function, trimming of glucose residues off the core oligosaccharide added during N-linked glycosylation is a part of protein processing. If "overseer" enzymes note that residues are misfolded, proteins within the rER will re-add glucose residues so that other calreticulin/calnexin can bind to these proteins and prevent them from proceeding to the Golgi. This leads these aberrantly folded proteins down a path whereby they are targeted for degradation. Studies on transgenic mice reveal that calreticulin is a cardiac embryonic gene that is essential during development.
|
|
NF-κB is widely used by eukaryotic cells as a regulator of genes that control cell proliferation and cell survival. As such, many different types of human tumors have misregulated NF-κB: that is, NF-κB is constitutively active. Active NF-κB turns on the expression of genes that keep the cell proliferating and protect the cell from conditions that would otherwise cause it to die via apoptosis. In cancer, proteins that control NF- κB signaling are mutated or aberrantly expressed, leading to defective coordination between the malignant cell and the rest of the organism.
|
|
Zoptarelin doxorubicin (developmental code names AEZS-108, AN-152) consists of doxorubicin linked to a small peptide agonist to the luteinizing hormone- releasing hormone (LHRH) receptor. It has been developed as a potential treatment for a number of human cancers. The LHRH receptor is aberrantly present on the cell surface of approximately 80% of endometrial and ovarian cancers, 86% of prostate cancers and about 50% of breast cancers. Whereas in normal tissues, expression of this receptor is mainly confined to the pituitary gland, reproductive organs and hematopoietic stem cells.
|
|
Gunaydin started her lab at the University of San Francisco in 2016 and has since held an assistant professorship in Psychiatry as well as an appointment at the Institute for Neurodegenerative Diseases. In addition, Gunaydin is a member of the UCSF Neuroscience Graduate Program, the Kavli Institute for Fundamental Neuroscience, and in 2017 was named a Chan Zuckerberg Biohub Investigator. Gunaydin's lab aims to investigate the neural circuits underlying motivated behaviors and further understand how they aberrantly function in disease states. Gunaydin's lab is currently focusing on three main projects to address this aim.
|
|
When they inhibited PRC2, microglia exhibited robust phagocytic activity even in the absence of dying neurons. These findings highlighted a critical role for epigenetic regulation of microglia in diseases where aberrantly activated microglia lead to over-pruning and neurodegeneration. To understand more deeply what drives the unique epigenetic programming of cerebellar versus striatal microglia, Schaefer collaborated with Dr. Miriam Merad’s group at Sinai to look at ontology of cerebellar versus striatal microglia. They found that cerebellar microglial identity was driven by interactions between CSF-1 and the CSF-1 receptor, and was not reliant on the alternate CSF-1R ligand, IL-34.
|
|
The defective "protofilament" products apparently accumulate aberrantly, and thus form the distinctive whorled paranuclear inclusions that are characteristic of the rhabdoid cell. It seems likely that mutations and post-translational modifications affecting cytokeratin 8, cytokeratin 18, and vimentin protofilaments are intimately involved in the genesis of the characteristic inclusions and, therefore, of the rhabdoid phenotype. The particulars of this process are poorly understood, but depend in part on the origin of the tumor and stochastic genomic phenomena. Rhabdoid cells often express protein products suggestive of aggressive, dedifferentiated cells, including neuroendocrine tumor-related products and granulocyte-macrophage colony stimulating factor (GM-CSF).
|
|
Hepatocyte growth factor/Scatter Factor (HGF/SF) and its splicing isoform (NK1, NK2) are the only known ligands of the MET receptor. MET is normally expressed by cells of epithelial origin, while expression of HGF/SF is restricted to cells of mesenchymal origin. When HGF/SF binds its cognate receptor MET it induces its dimerization through a not yet completely understood mechanism leading to its activation. Abnormal MET activation in cancer correlates with poor prognosis, where aberrantly active MET triggers tumor growth, formation of new blood vessels (angiogenesis) that supply the tumor with nutrients, and cancer spread to other organs (metastasis).
|
|
NF-κB activity is tightly controlled by multiple proteins, which collectively ensure that only discrete clusters of genes are induced by NF-κB in a given cell and at a given time. This tight regulation of signal exchange between cells protects the tissue from excessive inflammation, and ensures that different cell types gradually acquire complementary functions and specific positions. Failure of this mutual regulation between genetic reprogramming and cell interactions allows cancer cells to give rise to metastasis. Cancer cells respond aberrantly to cytokines, and activate signal cascades that can protect them from the immune system.
|
|
Cancer is a complex, heterogeneous disease that can be hereditary or the result of environmental stimuli. Minigenes are used to help oncologists understand the roles pre-mRNA splicing plays in different cancer types. Of particular interest are cancer specific genetic mutations that disrupt normal splicing events, including those affecting spliceosome components and RNA-binding proteins such as heterogeneous nuclear ribonucleoparticules (hnRNP), serine/arginine-rich (SR) proteins and small ribonucleoproteins (snRNP). Proteins encoded by aberrantly spliced pre-mRNAs are functionally different and contribute to the characteristic anomalies exhibited by cancer cells, including their ability to proliferate, invade and undergo angiogenesis, and metastasis.
|
|
It occurs because the duration of the refractory period of the myocardium is proportional to the R-R interval of the preceding cycle. A short R-R interval is associated with a shorter duration of action potential and vice versa. A long R-R cycle will prolong the ensuing refractory period, and if a shorter cycle follows, the beat terminating the cycle is likely to be conducted aberrantly. Because the refractory period of the right bundle branch is longer than the left, the right bundle will still be in the refractory period when the supraventricular impulse reaches the His-Purkinje system, resulting in a complex with right bundle branch morphology.
|
|
Caspase-11 appears to provide immune defense against bacteria that enter or access the host cell cytosol. Caspase-11 has been shown to be activated by Burkholderia pseudomallei, Gram- negative bacteria found in the soil of southeast Asia that cause severe melioidosis. Caspase-11 has been shown in vitro to be activated by Shigella flexneri infection, while a guinea pig model of Shigella infection has been shown to activate the human homolog of caspase-11, caspase-4. For bacteria that do not typically access the host cytosol, caspase-11 is activated with delayed kinetics if Gram-negative bacteria aberrantly escape the vacuole and enter into the cytoplasm.
|
|
Not until the first decade of the next century, when the great (and popular) fantasist Maxfield Parrish worked his magic on the figure, would Pierrot be comfortably naturalized in America. Of course, writers from the United States living abroad--especially in Paris or London--were aberrantly susceptible to the charms of the Decadence. Such a figure was Stuart Merrill, who consorted with the French Symbolists and who compiled and translated the pieces in Pastels in Prose. Another was William Theodore Peters, an acquaintance of Ernest Dowson and other members of the Rhymers' Club and a driving force behind the conception and theatrical realization of Dowson's Pierrot of the Minute (1897; see England above).
|
|
In other scenarios and in contrast to the therapy outlined above, recent research suggests that HIF induction in normoxia is likely to have serious consequences in disease settings with a chronic inflammatory component. It has also been shown that chronic inflammation is self-perpetuating and that it distorts the microenvironment as a result of aberrantly active transcription factors. As a consequence, alterations in growth factor, chemokine, cytokine, and ROS balance occur within the cellular milieu that in turn provide the axis of growth and survival needed for de novo development of cancer and metastasis. These results have numerous implications for a number of pathologies where NF-κB and HIF-1 are deregulated, including rheumatoid arthritis and cancer.
|
|
Integration of sensory, emotional, and cognitive information allows for these diverse functions of the IC, so Gogolla sought to understand how this integration occurs and how it is aberrantly functioning in ASD models, both idiopathic and monogenic. Through in vivo fluorescence imaging techniques, Gogolla was able to record from the IC and observe multisensory integration emerging in the IC throughout early development, but this process did not occur in ASD models. She further found that expression of inhibitory neuron markers was decreased compared to controls in the IC of ASD mouse models suggesting that inhibitory/excitatory circuit balance is disrupted. Following this result, they pharmacologically enhanced inhibitory signalling in juvenile mice via systemic injections of diazepam for two weeks and found that it rescued integration deficits in ASD models.
|
|
Regulators of autophagy control regulators of inflammation, and vice versa. Cells of vertebrate organisms normally activate inflammation to enhance the capacity of the immune system to clear infections and to initiate the processes that restore tissue structure and function. Therefore, it is critical to couple regulation of mechanisms for removal of cellular and bacterial debris to the principal factors that regulate inflammation: The degradation of cellular components by the lysosome during autophagy serves to recycle vital molecules and generate a pool of building blocks to help the cell respond to a changing microenvironment. Proteins that control inflammation and autophagy form a network that is critical for tissue functions, which is dysregulated in cancer: In cancer cells, aberrantly expressed and mutant proteins increase the dependence of cell survival on the “rewired” network of proteolytic systems that protects malignant cells from apoptotic proteins and from recognition by the immune system.
|
|
After pioneering the use of PET imaging in the tracking and assessment of amyloid beta burden in the brains of AD patients, Price sought to use PET imaging to observe the Tau burden in AD patients as Tau deposition has been shown to be associated with neurodegeneration in various diseases. Price helped to improve the existing tools for PET imaging Tau by first debunking the idea that the common Tau PET ligand [F-18]AV-1451 aberrantly bind the choroid plexus leading to false positives. Price and her team explored the possible presence of tau tangles in the epithelial cells that line the choroid plexus and found that in fact they do contain tangles and they are labelled by tau antibodies as well. Price’s findings suggest that the previous reports of off target binding of [F-18]AV-1451 are actually just binding to brain boarder cells that are suffering from AD pathology.
|
|
Here, however, the eventual result is organ damage and often profound or even fatal disease, not resolution of the infection. An emerging concept is that IL-13 may antagonize Th1 responses that are required to resolve intracellular infections. In this immune dysregulated context, marked by the recruitment of aberrantly large numbers of Th2 cells, IL-13 inhibits the ability of host immune cells to destroy intracellular pathogens. IL-13 expression has demonstrated to be increased in bronchoalveolar lavage (BAL) fluid and cells in patients with atopic mild asthma after allergen challenge. Genome-wide association studies have identified multiple polymorphisms of IL-13 and genes encoding the IL-13 receptors as associated with asthma susceptibility, bronchial hyperresponsiveness, and increased IgE levels. The overexpression of IL-13 induces many features of allergic lung disease, including airway hyperresponsiveness, goblet cell metaplasia, mucus hypersecretion and airway remodelling which all contribute to airway obstruction. murine studies demonstrated that IL-13 was both necessary and sufficient to generate asthma-like Th2 responses in the mouse lung. IL-13 is mainly overexpressed in sputum, bronchial submucosa, peripheral blood and mast cells in the airway smooth muscle bundle.
|
|