The BPS Art of Science Image Contest took place again this year, during the 60th Annual Meeting in Los Angeles. The image that won second...
The epidermal growth factor (EGF) and its receptor (EGFR) constitute a well-characterized receptor-ligand system that plays an important role in the regulation of cell growth, proliferation, survival, and motility (1-4). EGFR is involved in oncogenic transformation, which can be caused by receptor overexpression, autocrine ligand loops, gene amplification, or activating mutations such as the EGFR type III deletion mutant (EGFRvIII; refs. 5-8).. In a global search for EGFR and EGFRvIII regulated genes, we recently found the mRNA level of the receptor tyrosine kinase EphA2 to be up-regulated by ligand-activated EGFR and the constitutively active variant EGFRvIII (9).. The cDNA sequence of EphA2 (previously known as epithelial cell kinase) was first described by Lindberg and Hunter in 1990 (10). EphA2 belongs to the Eph receptor family, which is the largest subfamily of receptor tyrosine kinases (11). Based on similarities in the extracellular domain sequences, the Eph receptors are divided into ...
2364 Lung cancer is the leading cause of cancer deaths worldwide. The development of improved systemic therapy is needed for those with the most common form of the disease, non-small cell lung cancer (NSCLC). This will depend on the identification of valid molecular targets. Recent studies point to the receptor tyrosine kinase EphA2 as a novel therapeutic target. EphA2 is commonly expressed in tumor tissue from patients with NSCLC, and its expression correlates with poor prognosis. However, these studies have only been carried out on a small number of patient samples. A more comprehensive assessment of EphA2 expression in NSCLC is currently needed. EphA2 may be particularly relevant in cancers with K-Ras mutations, which confer resistance to epidermal growth factor receptor (EGFR) therapy. RAS mutation leads to increased EphA2 expression in vitro. RAS-RAF-MAPK pathway activation via RAS mutation or EGFR activation is common in NSCLC. EphA2 has also been implicated in tumor angiogenesis, and ...
Purpose: : EphA receptors and ephrinA ligands are involved in nerve and vessel guidance during development, vascular cell assembly, and angiogenesis. Soluble ephrinA1-Fc has been reported to possess proangiogenic properties. Our purpose was to investigate the expression patterns of EphA and ephrinA in the cornea and in cultured mouse corneal cells. Methods: : SV40 T antigen-immortalized mouse corneal epithelial and keratocyte cell lines were generated and characterized using epithelial-/and keratocyte-specific markers. Confocal immunohistochemistry using antibodies against ephrinA ligands (ephrinA1, A2, A3, A4, or A5) and EphA receptors (EphA1, A2, A3, A4, A5, A6, A7, or A8) were used in vitro (immortalized wild type mouse corneal epithelial cells and keratocytes) and in vivo (normal mouse cornea). Results: : EphrinA1 and EphA3 were expressed mainly in normal mouse corneal epithelium. EphA1, A2, and A3 and ephrinA1 and A2 were expressed in corneal epithelial cell lines. EphA3 and ephrinA2 showed ...
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors. Protein Tyrosine Kinase (PTK) family; Ephrin Receptor (EphR) subfamily; most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, ...
EphA2 kinase regulates cell shape, adhesion, and motility and is frequently overexpressed in several cancers, including melanoma, prostate, breast, and colon cancers and lung carcinoma. Although a function in both tumor onset and metastasis has been proposed, the role played by EphA2 in tumor progression is still debated. In melanoma, EphA2 has been reported to affect cell migration and invasiveness allowing cells to move by a proteolysis-independent strategy, commonly referred as amoeboid motility. With the aim to understand the role of EphA2 in prostate cancer metastatic spreading, we stably silenced EphA2 expression in a model of aggressive metastatic prostate carcinoma. Our results show that EphA2 drives the metastatic program of prostate carcinoma, although its involvement greatly differs among metastatic steps. Indeed, EphA2 expression (i) greatly affects prostate carcinoma cell motility style, guiding an amoeboid movement based on Rho-mediated cell rounding and independent from ...
Buy 3-Keto-7α,12α-dihydroxy-5α-cholanic Acid (CAS 16265-24-0), a biochemical for proteomics research, from Santa Cruz. MF: C24H38O5
Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA Xinlong Zang,1 Huaiwei Ding,2 Xiufeng Zhao,3 Xiaowei Li,1 Zhouqi Du,1 Haiyang Hu,1 Mingxi Qiao,1 Dawei Chen,1 Yuihui Deng,1 Xiuli Zhao1 1Department of Pharmaceutics, School of Pharmacy, 2Department of Pharmaceutical Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 3Hongqi Hospital affiliated to Mudanjiang Medical University, Mudanjiang, People’s Republic of ChinaAbstract: Therapeutic delivery of small interfering RNA (siRNA) is a major challenge that limits its potential clinical application. Here, a pH-sensitive cholesterol–Schiff base–polyethylene glycol (Chol–SIB–PEG)-modified cationic liposome–siRNA complex, conjugated with the recombinant humanized anti-EphA10 antibody (Eph), was developed as an efficient nonviral siRNA delivery system. Chol–SIB–PEG was successfully
The present invention provides a method of screening for compounds which affect the processing of EphA4 by .gamma.-secretase, which includes the following steps: (i) contacting a first biological composition containing .gamma.-secretase or a biologically active fragment thereof with a second biological composition containing EphA4 in the presence and absence of a candidate compound; (ii) measuring the cleavage of the EphA4 in the presence and absence of the candidate compound; (iii) selecting those candidate compounds which affect the cleavage of the EphA4 by .gamma.-secretase; and (iv) identifying the candidate compounds selected in step (iii) as compounds which affect the processing of EphA4 by .gamma.-secretase.
Recent efforts in analyzing cancer genome have identified EPHA2 as one of the genes that are elevated in human lung cancer, and high levels of EPHA2 are associated with poor clinical outcomes. However, mechanistic basis for EPHA2 in lung cancer promotion remains poorly understood. In this study, we found that EPHA2 regulates tumor cell proliferation and motility through the JNK-c-JUN pathway. In addition, we provide evidence that EPHA2 is important for CSC function. Collectively, these data identified JNK/c-JUN as a major signaling pathway that is activated by oncogenic EPHA2 receptor in NSCLC, and a critical role for EPHA2 in CSCs.. Multiple intracellular signaling pathways have been linked to EPHA2 receptor in cancer cells (reviewed in refs. 2, 25). Ligand stimulation of EPHA2 has been shown to inhibit ERK and AKT phosphorylation, and tumor cell proliferation and motility in prostate and lung cancer cells, as well as in malignant glioma cells (11, 26, 27). Conversely, ligand-independent EPHA2 ...
Complete information for EPHA5 gene (Protein Coding), EPH Receptor A5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for EPHA5 gene (Protein Coding), EPH Receptor A5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
EphA7 est un membre de la famille des récepteurs à tyrosine kinase Eph, qui régulent ladhérence et la motilité cellulaires. EphA7 est hautement conservé chez les vertébrés et largement exprimé durant lembryogenèse, en particulier pendant le développement du SNC. Dans le cerveau adulte, EphA7 est transcrit principalement dans lhippocampe, avec de faibles niveaux dexpression ailleurs. Nous avons cartographié sa distribution dans le cerveau du rat et de la souris adultes, par hybridation in situ et immunohistochimie en microscopie photonique et électronique. Les deux méthodes montrent une distribution de marquage très cohérente. Le signal le plus fort a été observé dans lhippocampe, avec des niveaux moins élevés dans lhabénula, le striatum, lamygdale, les cortex cingulaire, piriforme et entorhinal, ainsi que le cervelet. Au niveau ultrastructural, dans lhippocampe, limmunoréactivité dEphA7 a été localisée dans le cytoplasme des cellules granulaires (gyrus ...
The major finding of our present study is that the EphA2 receptor tyrosine kinase is overexpressed in many ovarian cancers. We also showed that EphA2 overexpression relates to disease grade and survival and in particular, that EphA2 may provide independent information to guide evaluations of clinical outcome.. Our work breaks new ground in linking EphA2 with ovarian cancer. These results are consistent with studies of other epithelial carcinomas, in which EphA2 is not phosphorylated and has been described as an oncoprotein that critically controls tumor cell growth, survival, migration, invasiveness, and angiogenesis (5 , 20, 21, 22, 23, 24) . Overexpression of EphA2 has been noted in multiple epithelial carcinomas, including breast, melanoma, prostate, non-small-cell lung, and esophageal cancers (17, 18, 19, 20, 21) . To the best of our knowledge, our study is the first to evaluate the role of EphA2 in ovarian carcinoma, and its overexpression is predictive of aggressive ovarian cancer ...
Recombinant human EPHA2 (amino acids 561-end) was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag. EPHA2 is a member of the ephrin receptor subfamily of protein-tyrosine kinases that bind the ephrin-A ligand and have diverse cellular function.
Recombinant human EPHA3 (571-end) was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag. EPHA3 is a member of the ephrin receptor subfamily of protein-tyrosine kinases that bind the ephrin-A ligand and have diverse cellular function.
Mouse polyclonal antibody raised against a full-length human EPHA2 protein. EPHA2 (NP_004422.2, 1 a.a. ~ 976 a.a) full-length human protein. (H00001969-B02) - Products - Abnova
Rabbit polyclonal antibody raised against a full-length human EPHA10 protein. EPHA10 (AAH67734.1, 1 a.a. ~ 295 a.a) full-length human protein. (H00284656-D01P) - Products - Abnova
EphA3 Proteins and Enzymes available through Novus Biologicals. Browse our EphA3 Proteins and Enzyme catalog backed by our Guarantee+.
OBJECTIVE: To characterise the result of interleukin-4 (IL-4) around the biosynthesis of cyclo-oxygenases We (COX We) and II (COX II), the pace restricting enzymes of the formation of prostaglandin E2 (PGE2), in freshly ready rheumatoid synovial cells. decrease the mRNA focus of COX II in interleukin-1 alpha (IL-1 alpha) activated cultured synovial fibroblasts at passages … Read more OBJECTIVE: To characterise the result of interleukin-4 (IL-4) around the biosynthesis. Read More ...
EPHA1 (EPH receptor A1), Authors: Brett Stringer, Nirmitha Herath, Shannon Duffy, Mark Coulthard, Andrew Boyd. Published in: Atlas Genet Cytogenet Oncol Haematol.
Gene target information for EPHA3 - EPH receptor A3 (cattle). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
EphA2, EphrinAl expression in breast cancer and its relationship with clinical pathological study, Siyuan Bian, Bensi Zhang, Gui Yang, Qiandai Song, Yanjiao Li
By Sascha Marschang, Policy Manager for Health Systems, EPHA A recent conference in London, Antibiotics and Farming: Prescriptions for Change organised by the Alliance to Save our Antibiotics and Medact, explored the link between farming practices and drug-resistant infections in humans and animals. The event was timely in light of…
Supplementary Materialsfj. ITGB3, ITGAV, ITPR3, and EPHA2. Noteworthily, EPHA2 was necessary for myogenic differentiation, and it could promote myogenic differentiation through ERK signaling. Collectively, our research provided an understanding into the distinctive MBP profile between myogenic and adipogenic precursors in skeletal muscles and offered as a good basis for helping the function of MBPs in regulating differentiation.Zhang, X., Wang, L., Qiu, K., Xu, D., Yin, J. Active membrane proteome of adipogenic and myogenic precursors in skeletal muscles features EPHA2 may promote myogenic differentiation through ERK signaling. technique (29). TABLE 1 Primer sequences found in quantitative RT-PCR evaluation for 5 min at iced and 4C at ?80C for even more usage. MBPs had been extracted using Mem-PER Plus Membrane Proteins Extraction Package (89842; Thermo Fisher Scientific) based on the Cevipabulin fumarate producers instruction. Supernatant-containing cytosolic proteins had been attained after ...
Creative Biostructure has established a high-performance and ready-to-go platform for iterative crystallography service on Ephrin type-A receptor 2.
Selling tobacco, alcohol, and foods high in fat, salt and sugar (HFSS) is big business. Demand is booming, and with it, so are chronic, non-communicable diseases (NCDs). Unhealthy diet is the biggest risk factor for disability adjusted life years lost (DALYs) in the EU, principally through diabetes, cancer, and cardiovascular…
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EphA2, a member of Eph family receptor tyrosine kinases, is frequently overexpressed in a variety of human cancers, including breast cancers (Merlos-Suárez and Batlle, 2008; Pasquale, 2008). Overexpression of EphA2 is associated with an aggressive and metastatic cellular phenotype in breast cancers, and recent studies have revealed that EphA2 acts as a downstream effector of EGF receptors to promote cancer cell motility and invasion, independently of the ligand ephrin stimulation (Zelinski et al., 2001; Macrae et al., 2005; Larsen et al., 2007; Brantley-Sieders et al., 2008; Miao et al., 2009). Conversely, stimulation of EphA2 with its ligand ephrinA1 in cancer cells inhibits cell proliferation and migration (Miao et al., 2009). However, the mechanisms underlying the oncogenic effects of EphA2 remain poorly understood.. Rho family small GTPases play pivotal roles in the regulation of the actin cytoskeleton and cell migration and also contribute to many steps in cancer initiation and progression ...
The EphA4 receptor tyrosine kinase is a major regulator of axonal growth and astrocyte reactivity and is a possible inflammatory mediator. Given that multiple sclerosis (MS) is primarily an inflammatory demyelinating disease and in mouse models of MS, such as experimental autoimmune encephalomyelitis (EAE), axonal degeneration and reactive gliosis are prominent clinical features, we hypothesised that endogenous EphA4 could play a role in modulating EAE. EAE was induced in EphA4 knockout and wildtype mice using MOG peptide immunisation and clinical severity and histological features of the disease were then compared in lumbar spinal cord sections. EphA4 knockout mice exhibited a markedly less severe clinical course than wildtype mice, with a lower maximum disease grade and a slightly later onset of clinical symptoms. Numbers of infiltrating T cells and macrophages, the number and size of the lesions, and the extent of astrocytic gliosis were similar in both genotypes; however, EphA4 knockout mice ...
TY - JOUR. T1 - Epha2 genotype influences ultraviolet radiation induced cataract in mice. AU - Dave, Alpana. AU - Craig, Jamie E.. AU - Skrzypiec, Karina. AU - Quinn, Stephen. AU - Barnes, Mary. AU - Di Girolamo, Nick. AU - Mackey, David A.. AU - Burdon, Kathryn P.. AU - de Iongh, Robb U.. AU - Sharma, Shiwani. PY - 2019/11. Y1 - 2019/11. N2 - Age-related cataract is the major cause of blindness worldwide. Both genetic and environmental factors contribute to the disease. Genetic variation in the Ephrin type-A receptor 2 (EPHA2) gene is associated with the risk of age-related cataract in multiple populations, and exposure to ultraviolet-B (UV-B) radiation is a well-established risk factor for the disease. Epha2 knockout and UV-B radiation independently lead to cataract in mice, and UV-B radiation reportedly alters EPHA2 expression in cultured cells. We hypothesised that an interaction between UV-B radiation exposure and Epha2 signalling may influence cataract development. To test this hypothesis, ...
The gene encoding the mouse EphA8 receptor tyrosine kinase has been isolated from a mouse genomic library, and its complete genomic structure has been determined. This gene spans approximately 28 kb and consists of 17 exons. This gene structure is similar to the structure of the chick EphB2(Cek5) gene, except for one intron present between the first two exons encoding the EphA8 kinase domain. This difference may reflect an evolutionary divergence of the catalytic domain between EphA and EphB subgroup receptors. The site for transcription initiation has been mapped to the 19th nucleotide upstream from the translation start codon ATG. A feature of this gene is an unmethylated CpG island spanning exon 1 and the flanking sequence. The putative promoter of the EphA8 gene lacks a TATA box and contains multiple copies of the sequence GGGCGG, the core sequence of the putative Sp1-binding site. The 3.5-kb upstream genomic region containing part of the first exon showed strong promoter activity in ...
0046]Further, the polynucleotide encoding the EphA7 of the present invention includes a polynucleotide which hybridizes to a polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence as shown in SEQ ID NO: 7 or SEQ ID NO: 9 under stringent conditions and yet encodes a polypeptide having substantially the same activity as that of EphA7. The stringent conditions refer to, for example, 2×SSC, 0.1% SDS, 42° C. or 1×SSC, 0.1% SDS, 37° C. as washing conditions after hybridization. As more stringent conditions, 1×SSC, 0.1% SDS, 65° C. or 0.5×SSC, 0.1% SDS, 50° C. may be given, for example. More specifically, a method using Rapid-hyb buffer (Amersham Life Science) may be employed in which pre-hybridization is performed at 68° C. for more than 30 minutes; then, with addition of a probe, a hybrid is formed while keeping the reaction solution at 68° C. for more than 1 hour, followed by washing in 2×SSC, 0.1% SDS at room temperature for 20 minutes 3 ...
Resistance to immunotherapy is one of the biggest problems of current oncotherapeutics. While T cell abundance is essential for tumor responsiveness to immunotherapy, factors that define the T cell-inflamed tumor microenvironment are not fully understood. We used an unbiased approach to identify tumor-intrinsic mechanisms shaping the immune tumor microenvironment (TME), focusing on pancreatic adenocarcinoma because it is refractory to immunotherapy and excludes T cells from the TME. From human tumors, we identified ephrin-A receptor 2 (EPHA2) as a candidate tumor-intrinsic driver of immunosuppression. Epha2 deletion reversed T cell exclusion and sensitized tumors to immunotherapy. We found that prostaglandin endoperoxide synthase 2 (PTGS2), the gene encoding cyclooxygenase-2, lies downstream of EPHA2 signaling through TGF-β and is associated with poor patient survival. Ptgs2 deletion reversed T cell exclusion and sensitized tumors to immunotherapy; pharmacological inhibition of PTGS2 was ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Expression of EPHA8 (EEK, Hek3) in human tissue. Overview of the antibody staining with HPA031433 and CAB009660 in immunohistochemistry
Abnova Human EPHA4 Full-length ORF (NP_004429.1, 1 a.a. - 986 a.a.) Recombinant Protein with GST-tag at N-terminal 2µg Life Sciences:Protein Biology:Proteins:Proteins
Expression of EPHA4 (Hek8, TYRO1) in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers.
TY - JOUR. T1 - Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivo. AU - Kullander, K. AU - Mather, N K. AU - Diella, F. AU - Dottori, Mirella. AU - Boyd, Andrew W. AU - Klein, Rody. PY - 2001. Y1 - 2001. M3 - Article. VL - 29. SP - 73. EP - 84. JO - Neuron. JF - Neuron. SN - 0896-6273. ER - ...
The 1C1-mcMMAF immunoconjugate specifically bound to EphA2-positive HeyA8 cells but not to EphA2-negative cells and was internalized by HeyA8 cells. Treatment with 1C1-mcMMAF decreased the viability of HeyA8-luc cells in an EphA2-specific manner. In orthotopic mouse models, treatment with 1C1-mcMMAF inhibited tumor growth by 85%-98% compared with that in control mice (eg, for weight of HeyA8 tumors, 1C1-mcMMAF = 0.05 g and control = 1.03 g; difference = 0.98 g, 95% confidence interval [CI] = 0.40 to 1.58 g; P = .001). Even in bulkier disease models with HeyA8-luc cells, 1C1-mcMMAF treatment, compared with control treatment, caused regression of established tumors and increased survival of the mice (eg, 1C1-mcMMAF vs control, mean = 60.6 days vs 29.4 days; difference = 31.2 days, 95% CI = 27.6 to 31.2 days; P = .001). The antitumor effects of 1C1-mcMMAF therapy, in SKOV3ip1 tumors, for example, were statistically significantly related to decreased proliferation (eg, 1C1-mcMMAF vs control, mean = ...
EphA3 is expressed in solid tumors and leukemias and is an attractive target for the therapy. We have generated a panel of Humaneered® antibodies to the ligand-binding domain using a Fab epitope-focused library that has the same specificity as monoclonal antibody mIIIA4. A high-affinity antibody was selected that competes with the mIIIA4 antibody for binding to EphA3 and has an improved affinity of ∼1 nM. In order to generate an antibody with potent cell-killing activity the variable regions were assembled with human IgG1k constant regions and expressed in a Chinese hamster ovary (CHO) cell line deficient in fucosyl transferase ...
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Sigma-Aldrich offers abstracts and full-text articles by [Takahiro Sawada, Xuefeng Jing, Yueqiang Zhang, Emi Shimada, Hideyuki Yokote, Masayasu Miyajima, Kazushige Sakaguchi].
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Behr, M., Kaufmann, J.K., Ketzer, P., Engelhardt, S., Muck-Hausl, M., Okun, P.M., Petersen, G., Neipel, F., Hassel, J.C., Ehrhardt, A., Enk, A.H., Nettelbeck, D.M. (2014). Adenoviruses using the cancer marker EphA2 as a receptor in vitro and in vivo by genetic ligand insertion into different capsid scaffolds. PLoS One. 9, e95723 ...
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Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2. Protein Tyrosine Kinase (PTK) family; Ephrin Receptor (EphR) subfamily; EphA2 receptor; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The ...
Alzheimers disease is an age-dependent neurodegenerative disorder that is characterized by a progressive decline in cognitive function. γ-secretase dysfunction is evident in many cases of early onset familial Alzheimers disease. However, the mechanism by which γ-secretase dysfunction results in memory loss and neurodegeneration is not fully understood. Here, we demonstrate that γ-secretase is localized at synapses and regulates spine formation. We identify EphA4, one of the Ephrin receptor family members, as a substrate of γ-secretase, and find that EphA4 processing is enhanced by synaptic activity. Moreover, overexpression of EphA4 intracellular domain increases the number of dendritic spines by activating the Rac signaling pathway. These findings reveal a function for EphA4-mediated intracellular signaling in the morphogenesis of dendritic spines and suggest that the processing of EphA4 by γ-secretase affects the pathogenesis of Alzheimers disease ...
Journal of Oncology is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer. The journal provides a multidisciplinary forum for translational and clinical oncology research in the areas of molecular pathology, genomics, diagnosis and therapy, with a specific focus on molecular targeted agents and novel immune therapies.
Andretta E, Carton-Garcia F, Martinez-Barriocanal, de Marcondes PG, Jimenez-Flores LM, Macaya I, Bazzocco S, Bilic J, Rodrigues P, Nieto R, Landolfi S, Ramon Y
Absolutely free sterols seem to stabilize the constructions of mobile and intracellular membranes. Because the sheath of nerve fibres can be a deposit of numerous layers on the membranes of neighbouring cells, experienced mammalian nerve tissue (e.g., beef brain) would be the richest supply of cholesterol. Cholesterol also is transformed in animals to steroids which have a variety of crucial capabilities As well as in plants to steroids whose features are fewer Obviously comprehended. The bile acids (cholanoic acids, also known as cholanic acids) of higher vertebrates kind conjugates While using the amino acids taurine and glycine, and also the bile alcohols (cholane derivatives) of decrease animals variety esters with sulfuric acid (sulfates ...
Free of charge sterols show up to stabilize the structures of cellular and intracellular membranes. As the sheath of nerve fibres is really a deposit of numerous levels of the membranes of neighbouring cells, mature mammalian nerve tissue (e.g., beef Mind) is the richest source of cholesterol. Cholesterol is also converted in animals to steroids that have a range of essential features As well as in crops to steroids whose functions are a lot less Evidently understood. The bile acids (cholanoic acids, also referred to as cholanic acids) of bigger vertebrates type conjugates Together with the amino acids taurine and glycine, as well as bile alcohols (cholane derivatives) of reduce animals kind esters with sulfuric acid (sulfates ...
Indeed 123C4 increases survival in mice models of ALS, but acts as an EphA4 agonist and not antagonist, Pellecchia said, going on to explain that an agonist is a substance that stimulates chemical action, while an antagonist blocks such action. We show that 123C4 interacting with EphA4 causes the receptor to be internalized by a process known as endocytosis - a process initiated only by an agonist. We hypothesize that by inducing receptor internalization, 123C4 effectively removes EphA4 from the surface of motor neurons.. The transgenic mouse model Pellecchia and his colleagues used for the study has been widely adopted as a standard to select drug candidates as potential ALS therapeutics. But challenges lie ahead for Pellecchias team to bring 123C4 to the clinic to confirm that the laboratory studies effectively translate to patients affected by ALS.. As in any preclinical study, we must acknowledge that several obstacles are still in the way of translating agents like 123C4 into viable ...
In this study we adopted the guide-effector bispecific antibody design that we developed previously for cell-type-specific signaling modulation (8), and achieved cell-type-specific modulation of internalization. We show that when the guide-to-effector ratio crosses over a threshold (in our EphA2/ALCAM example, 1:5), a noninternalizing antigen (ALCAM) can be rendered internalizing by the bispecific. When the guide-to-effector ratio falls below the threshold, an internalizing antigen (EphA2) can be rendered non- or slowly internalizing by the bispecific. Thus in the context of bispecific targeting, the internalization behavior of a cell surface antigen is significantly impacted by its neighboring antigens, and can be readily manipulated in either direction through bispecific-based targeting of appropriately selected guide/effector pairs.. Our study has relevance to therapeutic development. In the direction of converting a noninternalizing into an internalizing antigen, our study has direct ...
The identification of a novel isoform of EphA4 and ITS expression in SOD1G93A mice. Zhao, Jing, Boyd, Andrew W. and Bartlett, Perry F. (2017) The identification of a novel isoform of EphA4 and ITS expression in SOD1G93A mice. Neuroscience, 347 11-21. doi:10.1016/j.neuroscience.2017.01.038. Australian brain alliance. Michie, Patricia T., Badcock, David R., Bartlett, Perry F., Bekkers, John M., Bourne, James A., Castles, Anne, Egan, Gary F., Fornito, Alex, Hannan, Anthony J., Hickie, Ian B., Mattingley, Jason B., Richards, Linda J., Schofield, Peter R., Shum, David H.K., Stuart, Greg J., Vickers, James C. and Vissel, Bryce (2016) Australian brain alliance. Neuron,92 3: 597-600. doi:10.1016/j.neuron.2016.10.038. Rejuvenating the brain: Aging with cognitive sparkle. Bartlett, Perry F. (2016) Rejuvenating the brain: Aging with cognitive sparkle. AQ - Australian Quarterly, 87 4: 24-29.. Elimination of the geomagnetic field stimulates the proliferation of mouse neural progenitor and stem cells. Fu, ...
NVP-BSK805 al., 2011; Lataillade et al., 2010; Simen, et al., 2009) Examples with sufficient HIV viral tons (typically >10,000 copies/mL) had been further examined for low-level resistant variations to 0.4% from the circulating viral quasi-species (Kozal MJ, et al., 2011; Lataillade, et al., 2010) that might have been skipped by regular genotyping strategies.(Kozal MJ, et al., 2011; Lataillade, et al., 2010; Li, et al., 2011; Simen, et al., 2009) Ultra-deep sequencing was still performed on examples with HIV viral tons bellow 10,000 copies/mL, nevertheless, NVP-BSK805 the degrees of mutations determined in these examples represent the percentage of sequenced PCR amplicons formulated with the mutation and could or might not represent the real percentage in the plasma test.(Kozal MJ, et al., 2011; Lataillade, et al., 2010) Test size and data evaluation A formal test size calculation had not been conducted because of this cross-sectional evaluation. We expected a prevalence of HIV medication level ...
Supplementary MaterialsAdditional document 1 Summary of the HPV16-specific proliferative responses measured by the lymphocyte stimulation assay. adaptive immune system permitting the development of an HPV16-synthetic long peptide (SLP) vaccine with an excellent treatment profile in animal models. Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced […]. ...
Presentation of Steier eck, located in Malia in Crete. The Restaurant Steier Eck is located on the point between the historical Old City and the unique beachside road of Malia. It is located in the center of Malia Town, which is a great touristic area - resort. The restaurant offer...
SWISS-MODEL Template Library (SMTL) entry for 5nk7.1. Crystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase with Compound 2a
Analysis of mouse EphA knockins and knockouts suggests that retinal axons programme target cells to form ordered retinotopic maps ...
Z kladn m pracovn m n strojom be ca je v ka dom ro nom obdob jeho noha. Je z kladom dr ania tela, zdrojom pohybu, odrazu a kontaktu s povrchom, na ktorom sa pohybuje.
Im very happy, Papelbon said before last nights game. Im not worried at all. Thats like I said yesterday - Ill let [NESN broadcasters] Tom Caron and Dennis Eckersley (above) worry about it. Im not worried about it. They seem to be more worried about it than I even am.. Heres the deal. Heres what everybody - including Tom and all the reporters - [expletive], Im a human. You know? Im not a machine. And, [expletive], a machine breaks down sometimes, too.. So I mean, theres that human factor for error. Youre going to be faced with that. Im going to be faced with that throughout my career and throughout the year.. Papelbons indifference toward critics, he said, stems from his self-analysis. He found a small measure of solace in his recent struggles, he said, because he improves more after a poor performance than a strong one.. Im going to be my hardest critic, Papelbon said. What you guys write in the paper, and what Dennis Eckersley and Tom Caron want to say, Im not doing ...
And The Economy - September 15, 2005A few new readers have asked whether I realize how dangerous it can be to have the Central Bank print too much money. Yes I do, as I will prove in a moment. But as you will see, there are other factors... ...
Ruijtenbeek, Rob; Kruijtzer, John A. W.; van De Wiel, Wendy; Fischer, Marcel J. E.; Flüeck, Martin; Redegeld, Frank A. M.; Liskamp, Rob M. J.; et al. ...