559 research outputs found
Genetic control of mammalian T-cell proliferation with a synthetic RNA regulatory system - illusion or reality?
Synthetic RNA-based regulatory systems are used to program higher-level biological functions that could be exploited, among many applications, for in vivo diagnostic and therapeutic applications. Chen and colleagues have recently reported a significant technological advance by producing an RNA modular device based on a hammerhead ribozyme and successfully tested its ability to control the proliferation of mammalian T lymphocytes. Like all exciting research, this work raises a lot of significant questions. How quickly will such knowledge be translated into clinical practice? How efficient will this system be in human clinical trials involving adaptive T-cell therapy? We discuss the possible advantages of using such new technologies for specific therapeutic applications
High glucose induces MCP-1 expression partly via tyrosine kinaseāAP-1 pathway in peritoneal mesothelial cells
High glucose induces MCP-1 expression partly via tyrosine kinaseāAP-1 pathway in peritoneal mesothelial cells.BackgroundHigh glucose in peritoneal dialysis solutions has been implicated in the pathogenesis of peritoneal fibrosis in chronic ambulatory peritoneal dialysis (CAPD) patients. However, the mechanisms are not very clear. Peritoneal macrophages seem to participate in the process of peritoneal fibrosis and monocyte chemoattractant protein-1 (MCP-1) plays a key role in the recruitment of monocytes toward the peritoneal cavity. However, little is known about the effect of high glucose on MCP-1 expression and its signal transduction pathway in human peritoneal mesothelial cells.MethodsMesothelial cells were cultured with glucose (5 to 100 mmol/L) or mannitol chronically for up to seven days. MCP-1 expression of mRNA and protein was measured by Northern blot analysis and enzyme-linked immunosorbent assay (ELISA). Chemotactic activity of high-glucoseāconditioned culture supernatant was measured by chemotactic assay. To examine the roles of the transcription factors activator protein-1 (AP-1) and nuclear factor-ĪŗB (NF-ĪŗB), electrophoretic mobility shift assay (EMSA) was performed.ResultsGlucose induced MCP-1 mRNA expression in a time- and dose-dependent manner. MCP-1 protein in cell culture supernant was also increased. Equivalent concentrations of mannitol had no significant effect. High-glucoseāconditioned supernatant possessed an increased chemotactic activity for monocytes, which was neutralized by antiāMCP-1 antibody. EMSA revealed that glucose increased the AP-1 binding activity in a time- and dose-dependent manner, but not NF-ĪŗB. Curcumin, an inhibitor of AP-1, dose-dependently suppressed the induction of MCP-1 mRNA by high glucose. Tyrosine kinase inhibitors such as genistein (12.5 to 50 Ī¼mol/L) and herbimycin A (0.1 to 1 Ī¼mol/L) inhibited the high-glucoseāinduced MCP-1 mRNA expression in a dose-dependent manner, and also suppressed the high-glucoseāinduced AP-1 binding activity.ConclusionsHigh glucose induced mesothelial MCP-1 expression partly via the tyrosine kinase-AP-1 pathway
Activation of spleen tyrosine kinase is required for TNF-Ī±-induced endothelin-1 upregulation in human aortic endothelial cells
AbstractEndothelin-1 (ET-1) promotes atherosclerosis. We tested whether spleen tyrosine kinase (Syk) mediates tumor necrosis factor-Ī± (TNF-Ī±)-induced ET-1 upregulation in human aortic endothelial cells (HAECs) and sought to identify the signal pathways involved. TNF-Ī±-induced reactive oxygen species (ROS) activated Syk and phosphatidylinositol 3-kinase (PI3K), which was required for the activation of AP-1 and subsequent ET-1 gene transcription. ROS mediated c-Jun NH2-terminal kinase (JNK) is also required for AP-1 activation, but Syk and PI3K regulated AP-1 activation independently of JNK. Through regulation of ET-1 production, Syk could be implicated in atherosclerosis
KMT-2016-BLG-1107: A New Hollywood-Planet Close/Wide Degeneracy
We show that microlensing event KMT-2016-BLG-1107 displays a new type of
degeneracy between wide-binary and close-binary Hollywood events in which a
giant-star source envelops the planetary caustic. The planetary anomaly takes
the form of a smooth, two-day "bump" far out on the falling wing of the light
curve, which can be interpreted either as the source completely enveloping a
minor-image caustic due to a close companion with mass ratio , or
partially enveloping a major-image caustic due to a wide companion with
. The best estimates of the companion masses are both in the planetary
regime ( and ) but differ by an even larger factor than the mass ratios due to
different inferred host masses. We show that the two solutions can be
distinguished by high-resolution imaging at first light on next-generation
("30m") telescopes. We provide analytic guidance to understand the conditions
under which this new type of degeneracy can appear.Comment: 23 pages, 7 figures, accepted for publication in A
Clarithromycin Susceptibility Testing of Mycobacterium avium Complex Using 2,3-Diphenyl-5-thienyl-(2)-tetrazolium Chloride Microplate Assay with Middlebrook 7H9 Broth
A series of 119 Mycobacterium avium complex isolates were subjected to clarithromycin susceptibility testing using microplates containing 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC). Among 119 isolates, 114 (95.8%) were susceptible to clarithromycin and 5 were resistant according to the new and the standard method. STC counts the low cost and reduces the number of procedures needed for susceptibility testing
KMT-2018-BLG-1990Lb: A Nearby Jovian Planet From A Low-Cadence Microlensing Field
We report the discovery and characterization of KMT-2018-BLG-1990Lb, a Jovian
planet orbiting a late M dwarf
, at a distance
(D_L=1.23_{-0.43}^{+1.06}\,\kpc), and projected at times the
snow line distance, i.e., a_{\rm snow}\equiv 2.7\,\au (M/M_\odot), This is
the second Jovian planet discovered by KMTNet in its low cadence () fields, demonstrating that this population will be well
characterized based on survey-only microlensing data.Comment: 24 pages, 7 figures, 4 table
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