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排序方式: 共有123条查询结果,搜索用时 15 毫秒
71.
72.
Caruana G Cullen-McEwen L Nelson AL Kostoulias X Woods K Gardiner B Davis MJ Taylor DF Teasdale RD Grimmond SM Little MH Bertram JF 《Gene expression patterns : GEP》2006,6(8):807-825
The E11.5 mouse metanephros is comprised of a T-stage ureteric epithelial tubule sub-divided into tip and trunk cells surrounded by metanephric mesenchyme (MM). Tip cells are induced to undergo branching morphogenesis by the MM. In contrast, signals within the mesenchyme surrounding the trunk prevent ectopic branching of this region. In order to identify novel genes involved in the molecular regulation of branching morphogenesis we compared the gene expression profiles of isolated tip, trunk and MM cells using Compugen mouse long oligo microarrays. We identified genes enriched in the tip epithelium, sim-1, Arg2, Tacstd1, Crlf-1 and BMP7; genes enriched in the trunk epithelium, Innp1, Itm2b, Mkrn1, SPARC, Emu2 and Gsta3 and genes spatially restricted to the mesenchyme surrounding the trunk, CSPG2 and CV-2, with overlapping and complimentary expression to BMP4, respectively. This study has identified genes spatially expressed in regions of the developing kidney involved in branching morphogenesis, nephrogenesis and the development of the collecting duct system, calyces, renal pelvis and ureter. 相似文献
73.
Lu D Shen J Vil MD Zhang H Jimenez X Bohlen P Witte L Zhu Z 《The Journal of biological chemistry》2003,278(44):43496-43507
Vascular endothelial growth factor (VEGF) and its receptors have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. We previously identified several fully human neutralizing anti-VEGF receptor 2 (or kinase inserting domain-containing receptor (KDR)) antibodies from a large antibody phage display library. These antibodies bind specifically to KDR, block VEGF/KDR interaction, and inhibit VEGF-induced proliferation of human endothelial cells and migration of KDR+ leukemia cells. Three of these antibodies, interestingly, share an identical heavy chain variable (VH) sequence. In this report, we constructed a new library comprising the single VH paired with the variable light chain (VL) repertoire obtained from the original na?ve human library. Initial in vitro selection revealed that the single VH could pair with a number of different VL while retaining its specificity for KDR. However, a consensus VH/VL pair, clone 1121, was identified after three or four rounds of selection by tailoring the stringency of the panning conditions. Clone 1121 showed a >30-fold higher binding affinity to KDR (Kd, 100 pm) because of improvement on both association and dissociation constants and blocked VEGF/KDR interaction with an IC50 of approximately 1 nm, compared with that of 3-4 nm for the parent Fab fragments. Further, clone 1121 was more potent in inhibiting VEGF-stimulated KDR phosphorylation in endothelial cells. A binding epitope mapping study on clone 1121 and one of the parent clones, 2C6, demonstrated that both antibodies interacted with the third immunoglobulin domain within the extracellular region of KDR. Several peptide phage display libraries were utilized to further examine the fine binding specificities of the two antibodies. All of the 2C6-binding peptides are cysteine-constrained, whereas clone 1121 binds to both cysteine-constrained and linear peptides. It is noteworthy that most of the 2C6-binding peptides also cross-react with clone 1121, but none of the clone 1121-specific peptides binds to 2C6, indicating that clone 1121 retained part of the original binding epitope(s) of 2C6 while gaining new binding specificity. Taken together, our observation suggests that clone 1121 may have great clinical potential in anti-angiogenesis therapy. It further underscores the efforts to identify antibodies of high affinity for enhanced biological activities. 相似文献
74.
Carmen Parola Laura Salogni Xenia Vaira Sara Scutera Paolo Somma Valentina Salvi Tiziana Musso Giuseppe Tabbia Marco Bardessono Christian Pasquali Alberto Mantovani Silvano Sozzani Daniela Bosisio 《PloS one》2013,8(12)
OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), a product made of the water soluble fractions of 21 inactivated bacterial strain patterns responsible for respiratory tract infections, is used for the prevention of recurrent upper respiratory tract infections and acute exacerbations in chronic obstructive pulmonary disease patients. OM-85 is able to potentiate both innate and adaptive immune responses. However, the molecular mechanisms responsible for OM-85 activation are still largely unknown. Purpose of this study was to investigate the impact of OM-85 stimulation on human dendritic cell functions. We show that OM-85 selectively induced NF-kB and MAPK activation in human DC with no detectable action on the interferon regulatory factor (IRF) pathway. As a consequence, chemokines (i.e. CXCL8, CXCL6, CCL3, CCL20, CCL22) and B-cell activating cytokines (i.e. IL-6, BAFF and IL-10) were strongly upregulated. OM-85 also synergized with the action of classical pro-inflammatory stimuli used at suboptimal concentrations. Peripheral blood mononuclear cells from patients with COPD, a pathological condition often associated with altered PRR expression pattern, fully retained the capability to respond to OM-85. These results provide new insights on the molecular mechanisms of OM-85 activation of the immune response and strengthen the rational for its use in clinical settings. 相似文献
75.
The addition of an antiserum against Somatostatin (SRIF) to a culture of dispersed rat pituitary cells incubated in the presence of hypothalamic tissue enhances thyrotropin (TSH) secretion into the medium. This indicates that SRIF is normally secreted in amounts sufficient to affect TSH secretion and suggests that SRIF may be the agent responsible for the unexplained rapid termination of TSH secretion by thyrotrophs which have been activated by Thyrotropin Releasing Factor (TRF). 相似文献
76.
Gatsos X Perry AJ Anwari K Dolezal P Wolynec PP Likić VA Purcell AW Buchanan SK Lithgow T 《FEMS microbiology reviews》2008,32(6):995-1009
The assembly of beta-barrel proteins into membranes is a fundamental process that is essential in Gram-negative bacteria, mitochondria and plastids. Our understanding of the mechanism of beta-barrel assembly is progressing from studies carried out in Escherichia coli and Neisseria meningitidis. Comparative sequence analysis suggests that while many components mediating beta-barrel protein assembly are conserved in all groups of bacteria with outer membranes, some components are notably absent. The Alphaproteobacteria in particular seem prone to gene loss and show the presence or absence of specific components mediating the assembly of beta-barrels: some components of the pathway appear to be missing from whole groups of bacteria (e.g. Skp, YfgL and NlpB), other proteins are conserved but are missing characteristic domains (e.g. SurA). This comparative analysis is also revealing important structural signatures that are vague unless multiple members from a protein family are considered as a group (e.g. tetratricopeptide repeat (TPR) motifs in YfiO, beta-propeller signatures in YfgL). Given that the process of the beta-barrel assembly is conserved, analysis of outer membrane biogenesis in Alphaproteobacteria, the bacterial group that gave rise to mitochondria, also promises insight into the assembly of beta-barrel proteins in eukaryotes. 相似文献
77.
Viruses depend on the host cell to provide the energy and biomolecular subunits necessary for production of viral progeny. We have previously reported that human cytomegalovirus (HCMV) infection induces dramatic changes to central carbon metabolism, including glycolysis, the tricarboxylic acid (TCA) cycle, fatty acid biosynthesis, and nucleotide biosynthesis. Here, we explore the mechanisms involved in HCMV-mediated glycolytic activation. We find that HCMV virion binding and tegument protein delivery are insufficient for HCMV-mediated activation of glycolysis. Viral DNA replication and late-gene expression, however, are not required. To narrow down the list of cellular pathways important for HCMV-medicated activation of glycolysis, we utilized pharmaceutical inhibitors to block pathways reported to be both involved in metabolic control and activated by HCMV infection. We find that inhibition of calmodulin-dependent kinase kinase (CaMKK), but not calmodulin-dependent kinase II (CaMKII) or protein kinase A (PKA), blocks HCMV-mediated activation of glycolysis. HCMV infection was also found to target calmodulin-dependent kinase kinase 1 (CaMKK1) expression, increasing the levels of CaMKK1 mRNA and protein. Our results indicate that inhibition of CaMKK has a negligible impact on immediate-early-protein accumulation yet severely attenuates production of HCMV viral progeny, reduces expression of at least one early gene, and blocks viral DNA replication. Inhibition of CaMKK did not affect the glycolytic activation induced by another herpes virus, herpes simplex virus type 1 (HSV-1). Furthermore, inhibition of CaMKK had a much smaller impact on HSV-1 replication than on that of HCMV. These data suggest that the role of CaMKK during the viral life cycle is, in this regard, HCMV specific. Taken together, our results suggest that CaMKK is an important factor for HCMV replication and HCMV-mediated glycolytic activation. 相似文献
78.
Oluwadayo Oluwadara Luca Giacomelli Xenia Brant Russell Christensen Raisa Avezova George Kossan Francesco Chiappelli 《Bioinformation》2011,5(7):285-290
The evidence appears compelling that the microenvironment, and associated biological cellular and molecular factors, may contribute to the progression of
a variety of tumors. The effects of the microenvironment may directly influence the plasticity of T cell lineages, which was recently discussed (O''Shea &
Paul, 2010 [4]). To review the putative role of the microenvironment in modulating the commitment of tumor immune surveillance, we use the model of
oral premalignant lesions. 相似文献
79.
In the U.S., nasopharyngeal carcinoma (NpC) kills >7,600 each year. Deaths are predominantly among adult men, and in most cases, early detection and treatment can save lives. Despite the annual spending of approximately 3.2 billion dollars on head and neck cancer research, NpC remains a neglected disease since its fatality rates are among the lowest nation wide. The relative survival rates from NpC have not improved in the U.S. in the last 20 years. Infection with Epstein Barr Virus (EBV) is an important co-factor in the etiology of NpC. In other regions of the word (e.g., South-East Asia, Latin America), EBV infection and NpCrelated prevalence and mortality are substantially higher and more alarming. Epidemiological data indicate high prevalence of EBV infection and increased risk for NpC among Central and South American and Asian immigrants in the U.S., and also predict a sharp increase in NpC incidence in the next decade. To face this emerging threat, it is important to develop and validate novel modes of detection and intervention for NpC. To this end, we characterized the proteomic signature of NpC, and of the tumor infiltrating lymphocytes of the CD8+, activated (CD38+, mTOR+) and regulatory immune cell (FoxP3+) phenotype. Paraffinized biopsies were processed, and tissue microarrays constructed and tested by immunohistochemistry and triimmunohistofluorescence for a battery of signaling markers, including AKT and PI3K, in conjunction with EBV status and ANKRD11, an NpC susceptibility biomarker. Microphotographs, analyzed and quantified by confocal microscopy and fractal analysis, suggest new avenues for immunotherapies of NpC. 相似文献
80.
Galina Dvoriantchikova Isabel Perea-Martinez Steve Pappas Ariel Faye Barry Dagmara Danek Xenia Dvoriantchikova Daniel Pelaez Dmitry Ivanov 《PloS one》2015,10(6)
The oscillatory expression of Notch signaling in neural progenitors suggests that both repressors and activators of neural fate specification are expressed in the same progenitors. Since Notch1 regulates photoreceptor differentiation and contributes (together with Notch3) to ganglion cell fate specification, we hypothesized that genes encoding photoreceptor and ganglion cell fate activators would be highly expressed in Notch1 receptor-bearing (Notch1+) progenitors, directing these cells to differentiate into photoreceptors or into ganglion cells when Notch1 activity is diminished. To identify these genes, we used microarray analysis to study expression profiles of whole retinas and isolated from them Notch1+ cells at embryonic day 14 (E14) and postnatal day 0 (P0). To isolate Notch1+ cells, we utilized immunomagnetic cell separation. We also used Notch3 knockout (Notch3KO) animals to evaluate the contribution of Notch3 signaling in ganglion cell differentiation. Hierarchical clustering of 6,301 differentially expressed genes showed that Notch1+ cells grouped near the same developmental stage retina cluster. At E14, we found higher expression of repressors (Notch1, Hes5) and activators (Dll3, Atoh7, Otx2) of neuronal differentiation in Notch1+ cells compared to whole retinal cell populations. At P0, Notch1, Hes5, and Dll1 expression was significantly higher in Notch1+ cells than in whole retinas. Otx2 expression was more than thirty times higher than Atoh7 expression in Notch1+ cells at P0. We also observed that retinas of wild type animals had only 14% (P < 0.05) more ganglion cells compared to Notch3KO mice. Since this number is relatively small and Notch1 has been shown to contribute to ganglion cell fate specification, we suggested that Notch1 signaling may play a more significant role in RGC development than the Notch3 signaling cascade. Finally, our findings suggest that Notch1+ progenitors—since they heavily express both pro-ganglion cell (Atoh7) and pro-photoreceptor cell (Otx2) activators—can differentiate into either ganglion cells or photoreceptors. 相似文献