Search results for "Signal"
showing 10 items of 6924 documents
Regulation of the hDlg/hScrib/Hugl-1 tumour suppressor complex.
2008
The proper function of the Scribble tumour suppressor complex is dependent upon the correct localisation of its components. Previously we observed dynamic relocalisation of the hDlg component under conditions of osmotic stress. We now show that the other two components of the complex, hScrib and Hugl-1 display similar patterns of expression. We demonstrate, by shRNA ablation of hScrib expression, that hDlg and Hugl-1 are in part dependent upon hScrib for their correct localization. However under conditions of osmotic stress this apparent dependency no longer exists: hDlg and Hugl-1 localise to cell membranes independently of hScrib. We also demonstrate an interaction between the three compo…
Design Considerations of Transverse Flux Generator to Sea Wave Energy
2014
In this paper we study the possibility to use a transverse flux linear generator (TFG) because transverse flux technology presents the highest force density per volume index among the iron based electrical machines. This paper is organized as follows an introduction to describe "state of the art" of WEC's and TFG, in the Section II we find a summary description of the marine condition of the chosen site; in the Section III there is an the analytical procedure for geometric and magnetic design of device (chosen material, length, etc) and in the Section IV the simulation of generator. Further defined the design of the generator, the machine was designed and analyzed through the use of a 3D FE…
Expression of the ALS-causing variant hSOD1G93A leads to an impaired integrity and altered regulation of claudin-5 expression in an in vitro blood–sp…
2015
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to the loss of primary and secondary motor neurons. Mutations in the Cu/Zn-superoxide dismutase (SOD1) gene are associated with familial ALS and to date numerous hypotheses for ALS pathology exist including impairment of the blood–spinal cord barrier. In transgenic mice carrying mutated SOD1 genes, a disrupted blood–spinal cord barrier as well as decreased levels of tight junction (TJ) proteins ZO-1, occludin, and claudin-5 were detected. Here, we examined TJ protein levels and barrier function of primary blood–spinal cord barrier endothelial cells of presymptomatic hSOD1G93…
Protein kinase CK2 governs the molecular decision between encephalitogenic T H 17 cell and T reg cell development
2016
T helper 17 (TH17) cells represent a discrete TH cell subset instrumental in the immune response to extracellular bacteria and fungi. However, TH17 cells are considered to be detrimentally involved in autoimmune diseases like multiple sclerosis (MS). In contrast to TH17 cells, regulatory T (Treg) cells were shown to be pivotal in the maintenance of peripheral tolerance. Thus, the balance between Treg cells and TH17 cells determines the severity of a TH17 cell-driven disease and therefore is a promising target for treating autoimmune diseases. However, the molecular mechanisms controlling this balance are still unclear. Here, we report that pharmacological inhibition as well as genetic ablat…
Generation of T Follicular Helper Cells Is Mediated by Interleukin-21 but Independent of T Helper 1, 2, or 17 Cell Lineages
2008
After activation, CD4(+) helper T (Th) cells differentiate into distinct effector subsets. Although chemokine (C-X-C motif) receptor 5-expressing T follicular helper (Tfh) cells are important in humoral immunity, their developmental regulation is unclear. Here we show that Tfh cells had a distinct gene expression profile and developed in vivo independently of the Th1 or Th2 cell lineages. Tfh cell generation was regulated by ICOS ligand (ICOSL) expressed on B cells and was dependent on interleukin-21 (IL-21), IL-6, and signal transducer and activator of transcription 3 (STAT3). However, unlike Th17 cells, differentiation of Tfh cells did not require transforming growth factor beta (TGF-beta…
STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.
2009
Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific d…
Suppressor of cytokine signaling 3 sensitizes anaplastic thyroid cancer to standard chemotherapy
2009
We previously showed that cancer cells from papillary, follicular, and anaplastic thyroid carcinomas produce interleukin-4 and interleukin-10, which counteract the cytotoxic activity of conventional chemotherapy through the up-regulation of antiapoptotic molecules. Here, we identify Janus kinase/signal transducers and activators of transcription (STAT) and phosphatidyl inositol 3-kinase (PI3K)/AKT as the down-stream pathways through which these cytokines confer resistance to cell death in thyroid cancer. We found that the absence of suppressors of cytokine signaling (SOCS) molecules allows the propagation of the survival signaling. Exogenous expression of SOCS1, SOCS3, and SOCS5 in the high…
Signaling molecules: the pathogenic role of the IL-6/STAT-3 trans signaling pathway in intestinal inflammation and in colonic cancer.
2008
Although the precise etiology of inflammatory bowel diseases (IBD) still remains unclear, considerable progress has been made in the identification of novel signal transduction pathways that elucidate the immunopathogenesis involved in the perpetuation of the inflammatory process. As both ulcerative colitis and Crohn's disease are associated with an increased risk for developing colorectal cancer (CRC) and precancerous dysplastic epithelial changes, further studies have concentrated on finding a common signaling pathway that could serve as a mechanistic link between inflammation and associated colonic cancer in IBD. This review presents the current data concerning the pathogenic role of the…
Effect of LIF-withdrawal on acetylcholine synthesis in the embryonic stem cell line CGR8 is not mediated by STAT3, PI3Ks or cAMP/PKA pathways.
2015
Acetylcholine (ACh) acts as a local cellular signaling molecule and is widely expressed in nature, including mammalian cells and embryonic stem cells. The murine embryonic stem cell line CGR8 synthesizes and releases substantial amounts of ACh. Particularly during early differentiation - a period associated with multiple alterations in geno-/phenotype functions - synthesis and release of ACh are increased by 10-fold. In murine stem cells second messengers of the STAT-3, PI3K and cAMP/PKA pathways are involved in maintaining self-renewal and pluripotency. The present experiments were designed to test whether blockers of these signaling pathways enhance ACh cell content in the presence of LIF…
Socs3 induction by PPARγ restrains cancer-promoting inflammation
2013
The presence of proinflammatory cytokines in the tumor microenvironment can support further growth of established cancers. Docosahexaenoic acid (DHA), a peroxisome proliferator-activated receptor-gamma (PPARγ) ligand, has been shown to suppress inflammation and limit tumor progression in vivo. Are the anticancer properties of DHA relying on its ability to prevent inflammation? If so, what are the molecular links between the anti-inflammatory properties of DHA and its anticancer effects? DHA is an n-3 polyinsaturated fatty acid mainly found in fish oil that was shown to contribute to inflammation resolution by preventing the release of proinflammatory mediators in vivo.1 DHA has also been as…