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Pathway Components (pathway + component)
Selected AbstractsLongitudinal Effects of Hope on Depression and Anxiety: A Latent Variable AnalysisJOURNAL OF PERSONALITY, Issue 1 2007Randolph C. Arnau ABSTRACT This study tested the prospective effects of hope on depression and anxiety using a longitudinal design. A sample of 522 college students completed self-report measures of hope, depression, and anxiety at three time points, with 1-month delays between administrations. Structural equation modeling was employed to test two cross-lagged panel models of the reciprocal effects of the Agency and Pathways components of hope on depression and anxiety. Results indicated statistically significant negative effects for the Agency component of hope on later depression but no unique effect of the Pathways component of hope on depression. Likewise, Agency showed a statistically significant negative effect on later anxiety, but again Pathways had no significant influence on anxiety. In both cases, neither depression nor anxiety demonstrated any longitudinal effects on either the Agency or Pathways components of hope. Implications of these findings are discussed, along with potential directions for future research. [source] More than an accessory: implications of type III transforming growth factor-, receptor loss in prostate cancerBJU INTERNATIONAL, Issue 7 2010Seun Ajiboye The type III transforming growth factor-, receptor (TGF,R3, betaglycan), a tumour suppressor, is the most frequently lost TGF, pathway component. This event appears to be very important in the transition of the TGF, pathway from having tumour-suppressor activity in early prostate tumour development, to having tumour-promoting activity in metastatic disease. Moreover, loss of the TGF,R3 can also affect the cellular response towards testosterone, inhibin/activin, and dysregulate growth-factor pathways that mediate growth and angiogenesis. In this review we discuss how TGF,R3 normally functions as an accessory protein in the TGF, pathway, how its loss is related to tumour progression, and the treatment implications of TGF,R3 loss in individuals with prostate cancer. [source] Xenopus axin-related protein: A link between its centrosomal localization and function in the Wnt/,-catenin pathwayDEVELOPMENTAL DYNAMICS, Issue 1 2010Evguenia M. Alexandrova Abstract The Wnt/,-catenin signaling pathway regulates cell proliferation and cell fate determination in multiple systems. However, the subcellular localization of Wnt pathway components and the significance of this localization for the pathway regulation have not been extensively analyzed. Here we report that Xenopus Axin-related protein (XARP), a component of the ,-catenin destruction complex, is localized to the centrosome. This localization of XARP requires the presence of the DIX domain and an adjacent region. Since other components of the Wnt pathway have also been shown to associate with the centrosome, we tested a hypothesis that the ,-catenin destruction complex operates at the centrosome. However, XARP mutants with poor centrosomal localization revealed an enhanced rather than decreased ability to antagonize the Wnt/,-catenin pathway. Our data are consistent with the idea that the inactivation of XARP at the centrosome is an important regulatory point in Wnt signaling. Developmental Dynamics 239:261,270, 2010. © 2009 Wiley-Liss, Inc. [source] WNT signaling affects gene expression in the ventral diencephalon and pituitary gland growthDEVELOPMENTAL DYNAMICS, Issue 4 2008Mary Anne Potok Abstract We examined the role of WNT signaling in pituitary development by characterizing the pituitary phenotype of three WNT knockout mice and assessing the expression of WNT pathway components. Wnt5a mutants have expanded domains of Fgf10 and bone morphogenetic protein expression in the ventral diencephalon and a reduced domain of LHX3 expression in Rathke's pouch. Wnt4 mutants have mildly reduced cell differentiation, reduced POU1F1 expression, and mild anterior lobe hypoplasia. Wnt4, Wnt5a double mutants exhibit an additive pituitary phenotype of dysmorphology and mild hypoplasia. Wnt6 mutants have no obvious pituitary phenotype. We surveyed WNT expression and identified transcripts for numerous Wnts, Frizzleds, and downstream pathway members in the pituitary and ventral diencephalon. These findings support the emerging model that WNT signaling affects the pituitary gland via effects on ventral diencephalon signaling, and suggest additional Wnt genes that are worthy of functional studies. Developmental Dynamics 237:1006,1020, 2008. © 2008 Wiley-Liss, Inc. [source] Membrane binding of SRP pathway components in the halophilic archaea Haloferax volcaniiFEBS JOURNAL, Issue 7 2004Tovit Lichi Across evolution, the signal recognition particle pathway targets extra-cytoplasmic proteins to membranous translocation sites. Whereas the pathway has been extensively studied in Eukarya and Bacteria, little is known of this system in Archaea. In the following, membrane association of FtsY, the prokaryal signal recognition particle receptor, and SRP54, a central component of the signal recognition particle, was addressed in the halophilic archaea Haloferax volcanii. Purified H. volcanii FtsY, the FtsY C-terminal GTP-binding domain (NG domain) or SRP54, were combined separately or in different combinations with H. volcanii inverted membrane vesicles and examined by gradient floatation to differentiate between soluble and membrane-bound protein. Such studies revealed that both FtsY and the FtsY NG domain bound to H. volcanii vesicles in a manner unaffected by proteolytic pretreatment of the membranes, implying that in Archaea, FtsY association is mediated through the membrane lipids. Indeed, membrane association of FtsY was also detected in intact H. volcanii cells. The contribution of the NG domain to FtsY binding in halophilic archaea may be considerable, given the low number of basic charges found at the start of the N-terminal acidic domain of haloarchaeal FtsY proteins (the region of the protein thought to mediate FtsY,membrane association in Bacteria). Moreover, FtsY, but not the NG domain, was shown to mediate membrane association of H. volcanii SRP54, a protein that did not otherwise interact with the membrane. [source] Papillary and muscle invasive bladder tumors with distinct genomic stability profiles have different DNA repair fidelity and KU DNA-binding activitiesGENES, CHROMOSOMES AND CANCER, Issue 4 2009Johanne Bentley Low-grade noninvasive papillary bladder tumors are genetically stable whereas muscle invasive bladder tumors display high levels of chromosomal aberrations. As cells deficient for nonhomologous end-joining (NHEJ) pathway components display increased genomic instability, we sought to determine the NHEJ repair characteristics of bladder tumors and correlate this with tumor stage and grade. A panel of 13 human bladder tumors of defined stage and grade were investigated for chromosomal aberrations by comparative genomic hybridization and for NHEJ repair fidelity and function. Repair assays were conducted with extracts made directly from bladder tumor specimens to avoid culture-induced phenotypic alterations and selection bias as only a minority of bladder tumors grow in culture. Four noninvasive bladder tumors (pTaG2), which were genetically stable, repaired a partially incompatible double-strand break (DSB) by NHEJ-dependent annealing of termini and fill-in of overhangs with minimal loss of nucleotides. In contrast, four muscle invasive bladder cancers (pT2-3G3), which displayed gross chromosomal rearrangements, repaired DSBs in an error-prone manner involving extensive resection and microhomology association. Four minimally invasive bladder cancers (pT1G3) had characteristics of both repair types. Error-prone repair in bladder tumors correlated with reduced KU DNA-binding and loss of TP53 function. In conclusion, there were distinct differences in DSB repair between noninvasive papillary tumors and higher stage/grade invasive cancers. End-joining fidelity correlated with stage and was increasingly error-prone as tumors became more invasive and KU binding activity reduced; these changes may underlie the different genomic profiles of these tumors. © 2008 Wiley-Liss, Inc. [source] Differential expression of miRNAs in the visceral adipose tissue of patients with non-alcoholic fatty liver diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010M. Estep Aliment Pharmacol Ther 2010; 32: 487,497 Summary Background, Progression of non-alcoholic fatty liver disease (NAFLD) can be facilitated by soluble molecules secreted by visceral adipose tissue (VAT). MicroRNAs (miRNAs) are likely to regulate some of these molecular pathways involved in pathogenesis of NAFLD. Aim, To profile miRNA expression in the visceral adipose tissue of patients with NAFLD. Methods, Visceral adipose tissue samples were collected from NAFLD patients and frozen. Patients with biopsy-proven NAFLD were divided into non-alcoholic steatohepatitis (NASH) (n = 12) and non-NASH (n = 12) cohorts controlled for clinical and demographic characteristics. Extracted total RNA was profiled using TaqMan Human MicroRNA arrays. Univariate Mann,Whitney comparisons and multivariate regression analysis were performed to compare miRNA profiles. Results, A total of 113 miRNA differentially expressed between NASH patients and non-NASH patients (P < 0.05). Of these, seven remained significant after multiple test correction (hsa-miR-132, hsa-miR-150, hsa-miR-433, hsa-miR-28-3p, hsa-miR-511, hsa-miR-517a, hsa-miR-671). Predicted target genes for these miRNAs include insulin receptor pathway components (IGF1, IGFR13), cytokines (CCL3, IL6), ghrelin/obestatin gene, and inflammation-related genes (NFKB1, RELB, FAS). In addition, two miRNA species, hsa-miR-197 and hsa-miR-99, were significantly associated with pericellular fibrosis in NASH patients (P < 0.05). Levels of IL-6 in the serum negatively correlated with the expression levels of all seven miRNAs capable of down regulating IL-6 encoding gene. Conclusions, miRNA expression from VAT may contribute to the pathogenesis of NAFLD , a finding which may distinguish relatively simple steatosis from NASH. This could help identify potential targets for pharmacological treatment regimens and candidate biomarkers for NASH. [source] Emerging mechanisms in morphogen-mediated axon guidanceBIOESSAYS, Issue 10 2009Cristina Sánchez-Camacho Abstract Early in animal development, gradients of secreted morphogenic molecules, such as Sonic hedgehog (Shh), Wnt and TGF,/Bmp family members, regulate cell proliferation and determine the fate and phenotype of the target cells by activating well-characterized signalling pathways, which ultimately control gene transcription. Shh, Wnt and TGF,/Bmp signalling also play an important and evolutionary conserved role in neural circuit assembly. They regulate neuronal polarization, axon and dendrite development and synaptogenesis, processes that require rapid and local changes in cytoskeletal organization and plasma membrane components. A key question then is whether morphogen signalling at the growth cone uses similar mechanisms and intracellular pathway components to those described for morphogen-mediated cell specification. This review discusses recent advances towards the understanding of this problem, showing how Shh, Wnt and TGF,/Bmp have adapted their ,classical' signalling pathways or adopted alternative and novel molecular mechanisms to influence different aspects of neuronal circuit formation. [source] Pathway sensitivity analysis for detecting pro-proliferation activities of oncogenes and tumor suppressors of epidermal growth factor receptor-extracellular signal-regulated protein kinase pathway at altered protein levelsCANCER, Issue 18 2009Hu Li PhD Abstract BACKGROUND: Mathematic models and sensitivity analyses of biologic pathways have been used for exploring the dynamics and for detecting the key components of signaling pathways. METHODS: The authors previously developed a mathematic model of the epidermal growth factor receptor-extracellular signal-regulated protein kinase (EGFR-ERK) pathway using ordinary differential equations from existing EGFR-ERK pathway models. By using prolonged ERK activation as an indicator that may lead to cell proliferation under certain circumstances, in the current study, a pathway sensitivity analysis was performed to test its capability of detecting pro-proliferative activities through altered protein levels to examine the effects on ERK activation. RESULTS: The analysis revealed that 12 of 20 oncoproteins and 4 of 5 tumor suppressors were detected, consistent with reported experimental works. Because pathway dynamics depend on many factors, some of which were not included in the current models, failure to detect all known oncogenes and tumor suppressors can be because of the failure to include relevant crosstalk to other pathway components. CONCLUSIONS: Overall, the current results indicated that pathway sensitivity analysis is a useful approach for detecting and distinguishing pro-proliferation activities of oncoproteins and suppressed proliferative activities of tumor suppressors at altered protein levels at least in the EGFR-ERK model. Cancer 2009. © 2009 American Cancer Society. [source] Defective Jak,Stat activation in renal cell carcinoma is associated with interferon-, resistanceCANCER SCIENCE, Issue 8 2007Donghao Shang Chemotherapy is ineffective against metastatic renal cell carcinoma (RCC). Interferon (IFN)-, has become the most common agent used in clinical therapy to overcome this malignant tumor, although a satisfactory response has not been achieved and the mechanism of resistance of RCC to IFN-, remains unclear. The purpose of the present study was to evaluate the susceptibility of RCC cells to IFN-, and clarify the mechanism of IFN-, resistance in RCC. Six RCC cell lines and three types of IFN-, were used, and the expression, activation and effects of transfection of possible proteins or factors reported to be involved in IFN-, signaling were examined to clarify the mechanism of resistance. The results suggest that the resistance of RCC to IFN-, is associated with the lack of Jak1, Tyk2 and Stat1 expression and defective Jak,Stat activation, but not with a lack of IFN-, receptor, suppressors of cytokine signaling induction or other factors examined. Moreover, phosphorylation of Jak,Stat pathway components and reversion of IFN-, resistance in RCC were observed upon transfection with Jak1, Tyk2 or Stat1 vector. These results suggest that restoring the expression of Jak or Stat1 might strikingly increase the susceptibility of RCC to IFN-, and may be a new strategy for improving the response of RCC to IFN-, treatment. The Jak,Stat pathway should therefore be an appropriate target for the treatment of RCC. (Cancer Sci 2007; 98: 1259,1264) [source] | |||||||||||||