899 resultados para suppressor of cytokine signaling evolution
Resumo:
A central scheduling problem in wireless communications is that of allocating resources to one of many mobile stations that have a common radio channel. Much attention has been given to the design of efficient and fair scheduling schemes that are centrally controlled by a base station (BS) whose decisions depend on the channel conditions reported by each mobile. The BS is the only entity taking decisions in this framework. The decisions are based on the reports of mobiles on their radio channel conditions. In this paper, we study the scheduling problem from a game-theoretic perspective in which some of the mobiles may be noncooperative or strategic, and may not necessarily report their true channel conditions. We model this situation as a signaling game and study its equilibria. We demonstrate that the only Perfect Bayesian Equilibria (PBE) of the signaling game are of the babbling type: the noncooperative mobiles send signals independent of their channel states, the BS simply ignores them, and allocates channels based only on the prior information on the channel statistics. We then propose various approaches to enforce truthful signaling of the radio channel conditions: a pricing approach, an approach based on some knowledge of the mobiles' policies, and an approach that replaces this knowledge by a stochastic approximations approach that combines estimation and control. We further identify other equilibria that involve non-truthful signaling.
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The regulation of cell proliferation in the external granular layer (EGL) of the developing cerebellum is important for its normal patterning. An important signal that regulates EGL cell proliferation is Sonic hedgehog (Shh). Shh is secreted by the Purkinje cells (PC) and has a mitogenic effect on the granule cell precursors of the EGL. Deregulation of Shh signaling has been associated with abnormal development, and been implicated in medulloblastomas, which are tumors that arise from the cerebellum. Given the importance of the Shh pathway in cerebellum development and disease, there has been no systematic study of its expression pattern during human cerebellum development. In this study, we describe the expression pattern of Shh, its receptor patched, smoothened, and its effectors that belong to the Gli family of transcription factors, during normal human cerebellum development from 10 weeks of gestational age, and in medulloblastomas that represents a case of abnormal cell proliferation in the cerebellum. This expression pattern is compared to equivalent stages in the normal development of cerebellum in mouse, as well as in tumors. Important differences between human and mouse that reflect differences in the normal developmental program between the 2 species are observed. First, in humans there appears to be a stage of Shh signaling within the EGL, when the PC are not yet the source of Shh. Second, unlike in the postnatal mouse cerebellum, expression of Shh in the PC in the postnatal human cerebellum is downregulated. Finally, medulloblastomas in the human but not in patched heterozygote mouse express Shh. These results highlight cross-species differences in the regulation of the Shh signaling pathway.
Resumo:
The loss rate of linear momentum from a binary system composed of compact objects (radially falling towards each other under mutual gravitational influence) has been investigated using the multipolar post-Minkowskian approach. The 2.5PN accurate analytical formula for the linear momentum flux is provided, in terms of the separation of the two objects, in harmonic coordinates, both for a finite and an infinite initial separation. The 2.5PN formulas for the linear momentum flux are finally used to estimate the recoil velocity accumulated during a premerger phase of the binary evolution.
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Pathogenic rnycobacteria, including Mycobacterium tuberculosis and Mycobacterium bovis, cause significant morbidity and mortality worldwide. However, the vaccine strain Mycobacterium bovis BCG, unlike virulent strains, triggers extensive apoptosis of infected macrophages, a step necessary for the elicitation of robust protective immunity. We here demonstrate that M. bovis BCG triggers Toll-like receptor 2 (TLR2)-dependent microRNA-155 (miR-155) expression, which involves signaling cross talk among phosphatidylinositol 3-kinase (PI3K), protein kinase C delta (PKC delta), and mitogen-activated protein kinases (MAPKs) and recruitment of NF-kappa B and c-ETS to miR-155 promoter. Genetic and signaling perturbations presented the evidence that miR-155 regulates PKA signaling by directly targeting a negative regulator of PKA, protein kinase inhibitor alpha (PKI-alpha). Enhanced activation of PKA signaling resulted in the generation of PKA C-alpha; phosphorylation of MSK1, cyclic AMP response element binding protein (CREB), and histone H3; and recruitment of phospho-CREB to the apoptotic gene promoters. The miR-155-triggered activation of caspase-3, BAK1, and cytochrome c translocation involved signaling integration of MAPKs and epigenetic or posttranslational modification of histones or CREB. Importantly, M. bovis BCG infection-induced apoptosis was severely compromised in macrophages derived from miR-155 knockout mice. Gain-of-function and loss-of-function studies validated the requirement of miR-155 for M. bovis BCG's ability to trigger apoptosis. Overall, M. bovis BCG-driven miR-155 dictates cell fate decisions of infected macrophages, strongly implicating a novel role for miR-155 in orchestrating cellular reprogramming during immune responses to mycobacterial infection.
Resumo:
Madurai Block, the largest crustal block in the Southern Granulite Terrane (SGT) of Peninsular India, preserves the imprints of multistage tectonic evolution. Here, we present U-Pb and Hf isotope data on zircons from a charnockite-granite suite in the north-western part of this block. The oscillatory zoning, and the LREE to HREE enriched patterns of the zircons with positive Ce and negative Eu anomalies suggest that the zircon cores are of magmatic origin, with ages in the range of 2634-2435 Ma implying Neoarchean-Paleoproterozoic magmatism followed by subsequent metamorphism and protocontinent formation in the north-western part of the Madurai Block. A regional 550-500 Ma metamorphic overprint is also preserved in the zircons coinciding with the final amalgamation of the Gondwana supercontinent. The Hf isotopic data suggest that the granite and charnockite were derived from isotopically heterogeneous juvenile crustal domains and the charnockites show a significant contribution of mantle-derived components. Therefore, the Hf isotopic data reflect mixing of crustal and mantle-derived sources for the generation of Neoarchean crust in the north-western Madurai Block, possibly in a suprasubduction zone setting during continent building processes. (c) 2014 Elsevier Ltd. All rights reserved.
Resumo:
The effects of evaporation and the presence of agglomerating nanoparticles on the oscillation characteristics of pendant droplets are studied experimentally using ethanol and aqueous nanoalumina suspension, respectively. Axisymmetric oscillations induced by a round air jet are considered. Wavelet transform of the time evolution of the 2nd modal coefficient revealed that while a continuous increase in the natural frequency of the droplet occurs with time due to the diameter regression induced by vaporization in the case of ethanol droplet, no such change in resonant frequency occurs in the case of the agglomerating droplet. However, a gradual reduction in the oscillation amplitude ensues as the agglomeration becomes dominant. (C) 2014 Elsevier Ltd. All rights reserved.
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A new colorimetric probe has been developed for the detection and estimation of Pd-II at sub-nanomolar concentrations. The probe consisted of rhodamine (signaling unit), which was linked with a bis-picolyl moiety (binding site) through a phenyl ring. Pd-II induced opening of the spirolactam ring of the probe with the generation of a prominent pink color. The excellent selectivity of the probe towards Pd-II over Pd-0 or Rh-II ensured its potential utility for the detection of residual palladium contamination in pharma-ceutical drugs and in Pd-catalyzed reactions. The probe showed a ``turn-on'' (bright yellow) fluorescence upon the addition of Pd-II, which made it suitable for the detection of Pd contaminants in mammalian cells.
Resumo:
Tuberculosis is continuing as a problem of mankind. With evolution, MDR and XDR forms of tuberculosis have emerged from drug sensitive strain. MDR and XDR strains are resistant to most of the antibiotics, making the management more difficult. BCG vaccine is not providing complete protection against tuberculosis. Therefore new infections are spreading at a tremendous rate. At the present moment there is experimental evidence to believe that Vitamin A and Vitamin D has anti-mycobacterial property. It is in this context, we have hypothesized a host based approach using the above vitamins that can cause possible prevention and cure of tuberculosis with minimal chance of resistance or toxicity. (C) 2015 Elsevier Ltd. All rights reserved.
Resumo:
Zircon has been recognized as the unaltered part of the Earth's history which preserves nearly 4 billion year record of earth's evolution. Zircon preserves igneous and metamorphic processes during its formation and remains unaffected by sedimentary processes and crustal recycling. U-Pb and Lu-Hf in zircon work as geochronometer and geochemical tracer respectively. Zircon provide valuable information about the source composition of the rocks and the intrinsic details of an unseen crust-mantle processes. The world wide data of U-Pb and Lu-Hf isotope systems in zircon reveal crustal evolution through geological history. Moreover, the U-Pb age pattern of zircons show distinct peaks attributed to preservation of crustal rocks or mountain building during supercontinent assembly. The histogram of continental crust preservation shows that nearly one-third of continental crust was formed during the Archean, almost 20% was formed during Paleoproterozoic and 14% in last 400 Ma.
Resumo:
Activation of apoptosis signal regulating kinase 1 (ASK1)-p38 MAPK death signaling cascade is irn plicated in the death of dopaminergic neurons in substantia nigra in Parkinson's disease (PD). We investigated upstream activators of ASK1 using an MPTP mouse model of parkinsonism and assessed the temporal cascade of death signaling in ventral midbrain (VMB) and striatum (ST). MPTP selectively activated ASK1 and downstream 1)38 MAPK in a time dependent manner in VMB alone. This occurred through selective protein thiol oxidation of the redox-sensitive thiol disulfide oxidoreductase, thiorcdoxin (Trxl), resulting in release of its inhibitory association with ASK1, while glutathione-S-transferase ji 1 (GSTM1) remained in reduced form in association with ASK1. Levels of tumor necrosis factor (TNF), a known activator of ASK1, increased early after MPTP in VMB. Protein ovariation netvvork analysis (PCNA) using protein states as nodes revealed TNF to be an important node regulating the ASK1 signaling cascade. In confirmation, blocking MPTP-mecliated TNF signaling through intrathecal administration of TNFneutralizing antibody prevented Trxl oxidation and downstream ASK1-p38 MAPK activation. Averting an early increase in TNF, which leads to protein thiol oxidation resulting in activation of ASK1-p38 signaling, may be critical for neuroprotection in PD. Importantly, network analysis can help in understanding the cause/effect relationship within protein networks in complex disease states. (C) 2015 Published by Elsevier Inc.
Resumo:
The genus Glyphochloa (Poaceae: Panicoideae: Andropogoneae: Rottboellinae) is endemic to peninsular India and is distributed on lateritic plateaus of low and high altitude in and around Western Ghats and the Malabar Coast. The genus presumably originated and diversified in the Western Ghats. Species relationships in the genus Glyphochloa were deduced here based on molecular phylogenies inferred using nuclear ribosomal ITS sequences and plastid intergenic spacer regions (atpB-rbcL, trnT-trnL, trnL-trnF), and new observations were made of spikelet morphology, caryopsis morphology and meiotic chromosome counts. We observed two distinct clades of Glyphochloa s.l. One of these (group I') includes Ophiuros bombaiensis, and is characterized by a single-awned lower glume and a base chromosome number of 6; it grows in low elevation coastal areas. The other clade (group II') has a double-awned lower glume, a base chromosome number of 7, and is restricted to higher elevation lateritic plateaus; G. ratnagirica may belong to the group II clade, or may be a third distinct lineage in the genus. A sister-group relationship between group I and II taxa (with or without G. ratnagirica) is not well supported, although the genus is recovered as monophyletic in shortest trees inferred using ITS or concatenated plastid data. We present a key to species of Glyphochloa and make a new combination for O. bombaiensis.
Resumo:
The tribe Iphigenieae (Colchicaceace, Liliales) includes two genera, viz. Camptorrhiza and Iphigenia, which are distributed in Africa, India, and Australasia. Iphigenia is represented by 12 species, of which six occur in India while Camptorrhiza comprises one species each in Africa (C. strumosa) and India (C. indica). The genus Camptorrhiza possesses a knee-shaped tuber attached to the corms, filaments with a thick bulge in the middle and styles with single stigma. Iphigenia on the other hand lacks knee-shaped tuber, bears linear filaments and has styles with three stigmas. Camptorrhiza indica possesses ovoid corms, linear filaments and styles with a single stigma. These characters are intermediate between Iphigenia and Camptorrhiza and hence we studied the cytogenetics and phylogenetic placement of this species to ascertain its generic identity. Somatic chromosome count (2n = 22) and karyotypic features of C. indica are very similar to that of Iphigenia species. Molecular phylogenetic studies based on atpB-rbcL, rps16, trnL, and trnL-F regions showed that C. indica is nested within a lineage of Indian Iphigenia species. Thus, C. indica was reduced to a species of Iphigenia, i.e., I. ratnagirica. Camptorrhiza is now a monotypic genus restricted only to southern Africa. A key to the Indian Iphigenia species is provided. In addition, a new combination Wurmbea novae-zelandiae is proposed for Iphigenia novae-zelandiae.
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CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) are exploited by mycobacteria to subvert the protective host immune responses. The Treg expansion in the periphery requires signaling by professional antigen presenting cells and in particularly dendritic cells (DC). However, precise molecular mechanisms by which mycobacteria instruct Treg expansion via DCs are not established. Here we demonstrate that mycobacteria-responsive sonic hedgehog (SHH) signaling in human DCs leads to programmed death ligand-1 (PD-L1) expression and cyclooxygenase (COX)-2-catalyzed prostaglandin E-2 (PGE(2)) that orchestrate mycobacterial infection-induced expansion of Tregs. While SHH-responsive transcription factor GLI1 directly arbitrated COX-2 transcription, specific microRNAs, miR-324-5p and miR-338-5p, which target PD-L1 were downregulated by SHH signaling. Further, counter-regulatory roles of SHH and NOTCH1 signaling during mycobacterial-infection of human DCs was also evident. Together, our results establish that Mycobacterium directs a fine-balance of host signaling pathways and molecular regulators in human DCs to expand Tregs that favour immune evasion of the pathogen.
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Based on the three-dimensional elastic inclusion model proposed by Dobrovolskii, we developed a rheological inclusion model to study earthquake preparation processes. By using the Corresponding Principle in the theory of rheologic mechanics, we derived the analytic expressions of viscoelastic displacement U(r, t) , V(r, t) and W(r, t), normal strains epsilon(xx) (r, t), epsilon(yy) (r, t) and epsilon(zz) (r, t) and the bulk strain theta (r, t) at an arbitrary point (x, y, z) in three directions of X axis, Y axis and Z axis produced by a three-dimensional inclusion in the semi-infinite rheologic medium defined by the standard linear rheologic model. Subsequent to the spatial-temporal variation of bulk strain being computed on the ground produced by such a spherical rheologic inclusion, interesting results are obtained, suggesting that the bulk strain produced by a hard inclusion change with time according to three stages (alpha, beta, gamma) with different characteristics, similar to that of geodetic deformation observations, but different with the results of a soft inclusion. These theoretical results can be used to explain the characteristics of spatial-temporal evolution, patterns, quadrant-distribution of earthquake precursors, the changeability, spontaneity and complexity of short-term and imminent-term precursors. It offers a theoretical base to build physical models for earthquake precursors and to predict the earthquakes.
Resumo:
Numerical study of three-dimensional evolution of wake-type flow and vortex dislocations is performed by using a compact finite diffenence-Fourier spectral method to solve 3-D incompressible Navier-Stokes equations. A local spanwise nonuniformity in momentum defect is imposed on the incoming wake-type flow. The present numerical results have shown that the flow instability leads to three-dimensional vortex streets, whose frequency, phase as well as the strength vary with the span caused by the local nonuniformity. The vortex dislocations are generated in the nonuniform region and the large-scale chain-like vortex linkage structures in the dislocations are shown. The generation and the characteristics of the vortex dislocations are described in detail.