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11.
Glia maturation factor (GMF), a highly conserved brain-specific protein, isolated, sequenced and cloned in our laboratory.
Overexpression of GMF in astrocytes induces the production and secretion of granulocyte-macrophage-colony stimulating factor
(GM-CSF), and subsequent immune activation of microglia, expression of several proinflammatory genes including major histocompatibility
complex proteins, IL-1β, and MIP-1β, all associated with the development of experimental autoimmune encephalomyelitis (EAE),
the animal model for multiple sclerosis. Based on GMF’s ability to activate microglia and induce well-established proinflammatory
mediators, including GM-CSF, we hypothesize that GMF is involved in the pathogenesis of inflammatory disease EAE. In this
present investigation, using GMF-deficient mice, we study the role of GMF and how the lack of GMF affects the EAE disease.
Our results show a significant decrease in incidence, delay in onset, and reduced severity of EAE in GMF-deficient mice, and
support the hypothesis that GMF plays a major role in the pathogenesis of disease. 相似文献
12.
Hongwei Yu Bassam Wakim Man Li Brian Halligan G Stephen Tint Shailendra B Patel 《Proteome science》2007,5(1):17
Background
The low concentration and highly hydrophobic nature of proteins in lipid raft samples present significant challenges for the sensitive and accurate proteomic analyses of lipid raft proteins. Elimination of highly enriched lipids and interfering substances from raft samples is generally required before mass spectrometric analyses can be performed, but these procedures often lead to excessive protein loss and increased sample variability. For accurate analyses of the raft proteome, simplified protocols are needed to avoid excessive sample handling and purification steps. 相似文献13.
Influence of selected formulation variables on the preparation of enzyme-entrapped eudragit S100 microspheres 总被引:1,自引:0,他引:1
The aim of this work is to study the influence of formulation parameters in the preparation of sustained release enzyme-loaded Eudragit S100 microspheres by emulsion solvent diffusion technique. A 3(2) full factorial experiment was designed to study the effects of the amount of solvent (dichloromethane) and stabilizers (Tween 20, 40, or 80) on the drug content and microsphere size. The results of analysis of variance test for both effects indicated that the test is significant. The effect of amount of stabilizer was found to be higher on both responses (SS(Y1) = 45.60; SS(Y2) = 737.93), whereas solvent concentration comparatively produced significant effect on the size of microspheres (SS(Y1) = 0.81; SS(Y2) = 358.83). Scanning electron microscopy of microspheres with maximum drug content (2.5 mL dichloromethane and 0.1 mL Tween 80) demonstrated smooth surface spherical particles with mean diameter of 56.83 +/- 2.88 microm. The effect of formulation variables on the integrity of enzyme was confirmed by in vitro proteolytic activity. The enteric nature of microspheres was evaluated and results demonstrated ~6% to 7% release of enzyme in acidic medium. The release of enzyme from microspheres followed Higuchi kinetics. In phosphate buffer, microspheres showed an initial burst release of 20.34% +/- 2.35% in 1 hour with additional 58.79% +/- 4.32% release in the next 5 hours. Three dimensional response graphs were presented to visualize the effect of independent variables on the chosen response. Thus, Eudragit S100 microspheres can be successfully prepared for oral delivery of enzymes with desirable characters in terms of maximum loading and diffusion release pattern. 相似文献
14.
Swati Agarwal Shashi Kant Tiwari Brashket Seth Anuradha Yadav Anshuman Singh Anubha Mudawal Lalit Kumar Singh Chauhan Shailendra Kumar Gupta Vinay Choubey Anurag Tripathi Amit Kumar Ratan Singh Ray Shubha Shukla Devendra Parmar Rajnish Kumar Chaturvedi 《The Journal of biological chemistry》2015,290(34):21163-21184
The human health hazards related to persisting use of bisphenol-A (BPA) are well documented. BPA-induced neurotoxicity occurs with the generation of oxidative stress, neurodegeneration, and cognitive dysfunctions. However, the cellular and molecular mechanism(s) of the effects of BPA on autophagy and association with oxidative stress and apoptosis are still elusive. We observed that BPA exposure during the early postnatal period enhanced the expression and the levels of autophagy genes/proteins. BPA treatment in the presence of bafilomycin A1 increased the levels of LC3-II and SQSTM1 and also potentiated GFP-LC3 puncta index in GFP-LC3-transfected hippocampal neural stem cell-derived neurons. BPA-induced generation of reactive oxygen species and apoptosis were mitigated by a pharmacological activator of autophagy (rapamycin). Pharmacological (wortmannin and bafilomycin A1) and genetic (beclin siRNA) inhibition of autophagy aggravated BPA neurotoxicity. Activation of autophagy against BPA resulted in intracellular energy sensor AMP kinase (AMPK) activation, increased phosphorylation of raptor and acetyl-CoA carboxylase, and decreased phosphorylation of ULK1 (Ser-757), and silencing of AMPK exacerbated BPA neurotoxicity. Conversely, BPA exposure down-regulated the mammalian target of rapamycin (mTOR) pathway by phosphorylation of raptor as a transient cell''s compensatory mechanism to preserve cellular energy pool. Moreover, silencing of mTOR enhanced autophagy, which further alleviated BPA-induced reactive oxygen species generation and apoptosis. BPA-mediated neurotoxicity also resulted in mitochondrial loss, bioenergetic deficits, and increased PARKIN mitochondrial translocation, suggesting enhanced mitophagy. These results suggest implication of autophagy against BPA-mediated neurodegeneration through involvement of AMPK and mTOR pathways. Hence, autophagy, which arbitrates cell survival and demise during stress conditions, requires further assessment to be established as a biomarker of xenoestrogen exposure. 相似文献
15.
Raman Dhariwal Vijay Gahlaut Bhaganagare R. Govindraj Dharmendra Singh Saloni Mathur Shailendra Vyas Rajib Bandopadhyay Jitendra Paul Khurana Akhilesh Kumar Tyagi Kumble Vinod Prabhu Kunal Mukhopadhyay Harindra Singh Balyan Pushpendra Kumar Gupta 《Functional & integrative genomics》2015,15(2):233-245
16.
Similar to other bacteria, cyanobacteria exist in a wide-ranging diversity of shapes and sizes. However, three general shapes are observed most frequently: spherical, rod and spiral. Bacteria can also grow as filaments of cells. Some filamentous cyanobacteria have differentiated cell types that exhibit distinct morphologies: motile hormogonia, nitrogen-fixing heterocysts, and spore-like akinetes. Cyanobacterial cell shapes, which are largely controlled by the cell wall, can be regulated by developmental and/or environmental cues, although the mechanisms of regulation and the selective advantage(s) of regulating cellular shape are still being elucidated. In this review, recent insights into developmental and environmental regulation of cell shape in cyanobacteria and the relationship(s) of cell shape and differentiation to organismal fitness are discussed. 相似文献
17.
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) form a four-helix coiled-coil bundle that juxtaposes two bilayers and drives a basal level of membrane fusion. The Sec1/Munc18 (SM) protein binds to its cognate SNARE bundle and accelerates the basal fusion reaction. The question of how the topological arrangement of the SNARE helices affects the reactivity of the fusion proteins remains unanswered. Here we address the problem for the first time in a reconstituted system containing both SNAREs and SM proteins. We find that to be fusogenic a SNARE topology must support both basal fusion and SM stimulation. Certain topological combinations of exocytic SNAREs result in basal fusion but cannot support SM stimulation, whereas other topologies support SM stimulation without inducing basal fusion. It is striking that of all the possible topological combinations of exocytic SNARE helices, only one induces efficient fusion. Our results suggest that the intracellular membrane fusion complex is designed to fuse bilayers according to one genetically programmed topology. 相似文献
18.
The purpose of this research was to apply vacuum foam drying (VFD) for processing of LaSota virus and to screen formulation
additives for its stability. The aqueous dispersion of harvest containing sucrose or trehalose in combination with additive
(monosaccharides, polymers, N-Z-amine) was prepared. The diluted dispersions in vials were vacuum concentrated, foamed to
form a continuous structure, and vacuum dried. The products were evaluated for foam characteristics, residual moisture, virus
titer, x-ray diffraction pattern, and stability profile. The foamability increased with solid content in solutions. The foamability
of sucrose was enhanced with incorporation of N-Z-amine (10% and 15% wt/vol) and polyvinyl pyrrolidone (PVP K30, 3% wt/vol).
The fructose- or galactose-containing mixtures were deposited irregularly on the vial surface. The virus titer increased with
disaccharides in the formulation. Sucrose provided better protection than trehalose. Unlike lyophilization, N-Z-amine with
sucrose protected the virus from Millard’s Browning. Amino acids do not have a catalytic effect on hydrolysis of sucrose during
VFD. Monosaccharides were ineffective. A synergistic effect of PVP K30 or polyethylene glycol 6000 (3% wt/vol) with N-Z-amine
provided the maximum virus titer (6.97 and 7.15, respectively). This formulation retained the desired virus potency at 5°,
25°, and 40°C. The diffraction pattern revealed that a threshold concentration of N-Z-amine was required for inhibiting crystallization
of sucrose during VFD. VFD was successfully applied to produce a solid LaSota formulation. The products were amorphous and
did not devitrify on storage.
Published: July 21, 2006 相似文献
19.
Jingshi Shen Shailendra S. Rathore Lavan Khandan James E. Rothman 《The Journal of cell biology》2010,190(1):55-63
Sec1/Munc18 (SM) proteins activate intracellular membrane fusion through binding to cognate SNAP receptor (SNARE) complexes. The synaptic target membrane SNARE syntaxin 1 contains a highly conserved Habc domain, which connects an N-peptide motif to the SNARE core domain and is thought to participate in the binding of Munc18-1 (the neuronal SM protein) to the SNARE complex. Unexpectedly, we found that mutation or complete removal of the Habc domain had no effect on Munc18-1 stimulation of fusion. The central cavity region of Munc18-1 is required to stimulate fusion but not through its binding to the syntaxin Habc domain. SNAP-25, another synaptic SNARE subunit, contains a flexible linker and exhibits an atypical conjoined Qbc configuration. We found that neither the linker nor the Qbc configuration is necessary for Munc18-1 promotion of fusion. As a result, Munc18-1 activates a SNARE complex with the typical configuration, in which each of the SNARE core domains is individually rooted in the membrane bilayer. Thus, the SNARE four-helix bundle and syntaxin N-peptide constitute a minimal complement for Munc18-1 activation of fusion. 相似文献
20.
Mice with a targeted mutation of 3beta-hydroxysterol Delta(7)-reductase (Dhcr7) that cannot convert 7-dehydrocholesterol to cholesterol were used to identify the origin of fetal sterols. Because their heterozygous mothers synthesize cholesterol normally, virtually all sterols found in a Dhcr7 knockout fetus having a Delta(7) or a Delta(8) double bond must have been synthesized by the fetus itself but any cholesterol had to have come from the mother. Early in gestation, most fetal sterols were of maternal origin, but at approximately E13-14, in situ synthesis became increasingly important, and by birth, 55-60% of liver and lung sterols had been made by the fetus. In contrast, at E10-11, upon formation of the blood-brain barrier, the brain rapidly became the source of almost all of its own sterols (90% at birth). New, rapid, de novo sterol synthesis in brain was confirmed by the observation that concentrations of C24,25-unsaturated sterols were low in the brains of all very young fetuses but increased rapidly beginning at approximately E11-12. Reduced activity of sterol C24,25-reductase (Dhcr24) in brain, suggested by the abundance of C24,25-unsaturated compounds, seems to be the result of suppressed Dhcr24 expression. The early fetal brain also appears to conserve cholesterol by keeping cholesterol 24-hydroxylase expression low until approximately E18. 相似文献