Human immunodeficiency virus type 1 encoded viral protein Vpr is essential for infection of macrophages by HIV-1. Furthermore, these macrophages are resistant to cell death and are viral reservoir. However, the impact of Vpr on the macrophage proteome is yet to be comprehended. The goal of the present study was to use a stable-isotope labeling by amino acids in cell culture (SILAC) coupled with mass spectrometry-based proteomics approach to characterize the Vpr response in macrophages. Cultured human monocytic cells, U937, were differentiated into macrophages and transduced with adenovirus construct harboring the Vpr gene. More than 600 proteins were quantified in SILAC coupled with LC-MS/MS approach, among which 136 were significantly altered upon Vpr overexpression in macrophages. Quantified proteins were selected and clustered by biological functions, pathway and network analysis using Ingenuity computational pathway analysis. The proteomic data illustrating increase in abundance of enzymes in the glycolytic pathway (pentose phosphate and pyruvate metabolism) was further validated by western blot analysis. In addition, the proteomic data demonstrate down regulation of some key mitochondrial enzymes such as glutamate dehydrogenase 2 (GLUD2), adenylate kinase 2 (AK2) and transketolase (TKT). Based on these observations we postulate that HIV-1 hijacks the macrophage glucose metabolism pathway via the Vpr-hypoxia inducible factor 1 alpha (HIF-1 alpha) axis to induce expression of hexokinase (HK), glucose-6-phosphate dehyrogenase (G6PD) and pyruvate kinase muscle type 2 (PKM2) that facilitates viral replication and biogenesis, and long-term survival of macrophages. Furthermore, dysregulation of mitochondrial glutamate metabolism in macrophages can contribute to neurodegeneration via neuroexcitotoxic mechanisms in the context of NeuroAIDS. 相似文献
Summary Dantrolene-Na is a muscular relaxant which binds to sarcoplasmic reticulum (SR) with high affinity and decreases the availability of Ca2+ channels. The binding of fluorescent compounds, dantrolene-Na, nifedipine and chlortetracycline to the ciliary membrane ofParamecium aurelia has been studied. Dantrolene at the concentrations of 1.9 · 10–5, 3.8 · 10–5 and 7.9 · 10–5 M manifested a punctuated binding pattern to the cell membrane. Isolated cilia also bound dantrolene at their basal portion, whereas deciliated cell bodies lost their dotted binding pattern. Chlortetracycline showed a similar but weaker fluorescent staining. Nifedipine treated cells revealed no sign of fluorescent binding to the membrane and was only taken up in food vacuoles.Based on these observations we propose that dantrolene binding regular arrays ofParamecium cell membrane could be identical to granular plaques observed by electron microscope. The possible functioning of these structures as Ca2+ reservoirs is also discussed. 相似文献
The emergence of pathogenic bacteria resistant to multiple antimicrobial agents is turning into a major crisis in human and veterinary medicine. This necessitates a serious re-evaluation of our approaches toward antibacterial drug discovery and use. Concurrent advances in genomics including whole-genome sequencing, genotyping, and gene expression profiling have the potential to transform our basic understanding of antimicrobial pathways and lead to the discovery of novel targets and therapeutics. 相似文献
The relationship between serum anti-heat shock protein (Hsp)27 antibody and high sensitive C-reactive protein (hs-CRP) levels and indices of cardiac function were investigated in patients undergoing coronary artery bypass grafting (CABG) or heart valve replacement. The changes in anti-Hsp27 antibody titers and hs-CRP levels were compared among patients undergoing off-pump and on-pump CABG or valvular heart replacement. Fifty-three patients underwent off-pump, on-pump CABG, and heart valvular replacement in each group. Serum anti-Hsp27 titers and hs-CRP values were measured 24 h before and after the operation and at discharge. Echocardiography was performed before surgery and before discharge. The results were compared with values from 83 healthy controls. hs-CRP levels increased and anti-Hsp27 antibody decreased following surgery (P < 0.001 and P < 0.05, respectively), although these changes were independent of operative procedure (P = 0.361 and P = 0.120, respectively). Anti-Hsp27 antibody levels were higher at the time of discharge (P = 0.016). Only in coronary patients were anti-Hsp27 antibody levels negatively associated with E/E′ (r = −0.268, P = 0.022), a marker of pulmonary capillary wedge pressure. In conclusions, anti-Hsp27 antibody levels are associated with indices of cardiac function in coronary patients. Cardiopulmonary bypass had no significant effect on the induction of changes in anti-Hsp27 levels. Moreover, anti-Hsp27 antibody levels fell in all groups postoperatively; this may be due to the formation of immune complexes of antigen–antibody, and antibody levels were higher at the time of discharge.
Electronic supplementary material
The online version of this article (doi:10.1007/s12192-012-0358-y) contains supplementary material, which is available to authorized users. 相似文献
Lander-Waterman’s coverage bound establishes the total number of reads required to cover the whole genome of size G bases. In fact, their bound is a direct consequence of the well-known solution to the coupon collector’s problem which proves that for such genome, the total number of bases to be sequenced should be O(G ln G). Although the result leads to a tight bound, it is based on a tacit assumption that the set of reads are first collected through a sequencing process and then are processed through a computation process, i.e., there are two different machines: one for sequencing and one for processing. In this paper, we present a significant improvement compared to Lander-Waterman’s result and prove that by combining the sequencing and computing processes, one can re-sequence the whole genome with as low as O(G) sequenced bases in total. Our approach also dramatically reduces the required computational power for the combined process. Simulation results are performed on real genomes with different sequencing error rates. The results support our theory predicting the log G improvement on coverage bound and corresponding reduction in the total number of bases required to be sequenced. 相似文献
International Journal of Peptide Research and Therapeutics - Membrane proteins play important functions, such as cellular communication and transferring materials in the cell. Many membrane... 相似文献
International Journal of Peptide Research and Therapeutics - Acinetobacter baumannii is an important pathogen responsible for nosocomial infections worldwide. Trimeric autotransporters, the... 相似文献
Landscape and Ecological Engineering - The cities that are built on the arid biomes with the hot and dry climates can adjust the temperature (oasis effect) and create the urban cool island (UCI)... 相似文献
In this research work, a systematic design of a novel anti-reflective layer using embedded plasmonic nanoparticles is investigated for a thin-film GaAs solar cell. First, an anti-reflective layer that is made from ITO or SiO2 is assumed in which Al nanoparticles are embedded inside them to manipulate the absorption and hence the photocurrent of a 500-nm GaAs solar cell. It is investigated that the Al nanoparticles embedded inside the anti-reflective coating improve the photocurrent of a GaAs solar cell. For instance, the 15.37 mA photocurrent is obtained for 500-nm bare GaAs cell, and it reached to 17.25 mA/cm2 and 20.18 mA/cm2 when an ITO anti-reflection is used with Al nanoparticles on top and inside that, respectively. It increases to 21.94 mA/cm2 and 24.98 mA/cm2 in the case of the anti-reflective layer made from SiO2 and Al nanoparticles at the top side or inside that, respectively. Finally, using a double anti-reflective layer that is made from SiO2-TiO2, the maximum photocurrents of 23.79 mA/cm2 and 24.68 mA /cm2 are obtained when Al nanoparticles are at the top side or inside that, respectively. The simulation results show that the embedding Al nanoparticles in the anti-reflective layer can improve the photocurrent of a thin-film GaAs solar cell.
International Journal of Peptide Research and Therapeutics - Natural compounds extracted from marine organisms consisting of biological active materials like collagen provide a major source of... 相似文献