NTPase and 5′-RNA Triphosphatase Activities of Chikungunya Virus nsP2 Protein

Chikungunya virus (CHIKV) is an insect borne virus (genus: Alphavirus) which causes acute febrile illness in humans followed by a prolonged arthralgic disease that affects the joints of the extremities. Re-emergence of the virus in the form of outbreaks in last 6–7 years has posed a serious public health problem. CHIKV has a positive sense single stranded RNA genome of about 12,000 nt. Open reading frame 1 of the viral genome encodes a polyprotein precursor, nsP1234, which is processed further into different non structural proteins (nsP1, nsP2, nsP3 and nsP4). Sequence based analyses have shown helicase domain at the N-terminus and protease domain at C-terminus of nsP2. A detailed biochemical analysis of NTPase/RNA helicase and 5′-RNA phosphatase activities of recombinant CHIKV-nsP2T protein (containing conserved NTPase/helicase motifs in the N-terminus and partial papain like protease domain at the C-terminus) was carried out. The protein could hydrolyze all NTPs except dTTP and showed better efficiency for ATP, dATP, GTP and dGTP hydrolysis. ATP was the most preferred substrate by the enzyme. CHIKV-nsP2T also showed 5′-triphosphatase (RTPase) activity that specifically removes the γ-phosphate from the 5′ end of RNA. Both NTPase and RTPase activities of the protein were completely dependent on Mg2+ ions. RTPase activity was inhibited by ATP showing sharing of the binding motif by NTP and RNA. Both enzymatic activities were drastically reduced by mutations in the NTP binding motif (GKT) and co-factor, Mg2+ ion binding motif (DEXX) suggesting that they have a common catalytic site

FRUIT PEEL SOAP AND ITS ANTIBACTERIAL PROPERTIES IN SKIN CARE

Objective: To prepare soap under laboratory condition using fruit peels of Citrullus lanatus, Citrus lemon, Citrus maxima, Carica papaya, Ananas comosus and Punica granatum., to view the antibacterial property and pH of the soap prepared and to study the phytochemical content of the fruit peels. Methods: The homemade soap is prepared in the laboratory using fruit peelings. Antibacterial properties of the prepared soap were then tested using disc paper inhibition method against Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis. The Extract was prepared using distilled water and ethanol. The pH of the fruit peels was tested and screened for phytochemical properties. Results: Overall best results for the antibacterial property was shown by Citrullus lanatus, Carica papaya followed by Citrus aurantifolia and Ananas comosus for water extract. Citrus maxima followed by and Ananas comosus and Citrus aurantifolia for ethanol extract. All six fruit peels showed the presence of Alkaloids, Terpenes, Saponins, Glycosides, Quinones, and Tannins. pH of the soap ranges from 7-10. Conclusion: The peels of the fruit shows good results against the anti-bacterial activity for skin bacteria studied. Also, the soaps are less prone to the addition of the harmful chemicals and their derivatives

High on-off conductance switching ratio in light-driven self-assembled molecular devices

Date du colloque : 5-9/01/2010International audienc

What have human experimental overfeeding studies taught us about adipose tissue expansion and susceptibility to obesity and metabolic complications

What have human experimental overfeeding studies taught us about adipose tissue expansion and susceptibility to obesity and metabolic complication

Alternatives to immediate release tacrolimus in solid organ transplant recipients: When the gold standard is in short supply

Given the current climate of drug shortages in the United States, this review summarizes available comparative literature on the use of alternative immunosuppressive agents in adult solid organ transplant recipients including kidney, pancreas, liver, lung, and heart, when immediate‐release tacrolimus (IR‐TAC) is not available. Alternative options explored include extended‐release tacrolimus (ER‐TAC) formulations, cyclosporine, belatacept, mammalian target of rapamycin inhibitors, and novel uses of induction therapy for maintenance immunosuppression. Of available alternatives, only ER‐TAC formulations are of non‐inferior efficacy compared to IR‐TAC when used de novo or after conversion in stable kidney transplant recipients (KTRs). All other alternatives were associated with higher rates of biopsy‐proven rejection, but improved tolerance from classic adverse effects of IR‐TAC including nephrotoxicity and development of diabetes. While most alternative therapies are approved in KTRs, access via third‐party payors is an obstacle in non‐KTRs. In the setting of IR‐TAC shortage, alternate therapeutic options may be plausible depending on the organ population and individual patient situation to ensure appropriate, effective immunosuppression for each patient.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156148/2/ctr13903.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156148/1/ctr13903_am.pd

MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix composition

Abstract Background: Abdominal fat mass is associated with metabolic risk whilst gluteal femoral fat is paradoxically protective. MicroRNAs are known to be necessary for adipose tissue formation and function but their role in regulating human fat distribution remains largely unexplored. Methods: An initial microarray screen of abdominal subcutaneous and gluteal adipose tissue, with validatory qPCR, identified microRNA-196a as being strongly differentially expressed between gluteal and abdominal subcutaneous adipose tissue. Findings: We found that rs11614913, a SNP within pre-miR-196a-2 at the HOXC locus, is an eQTL for miR-196a expression in abdominal subcutaneous adipose tissue (ASAT). Observations in large cohorts showed that rs11614913 increased waist-to-hip ratio, which was driven specifically by an expansion in ASAT. In further experiments, rs11614913 was associated with adipocyte size. Functional studies and transcriptomic profiling of miR-196a knock-down pre-adipocytes revealed a role for miR-196a in regulating pre-adipocyte proliferation and extracellular matrix pathways. Interpretation: These data identify a role for miR-196a in regulating human body fat distribution.: This work was supported by the Medical Research Council and Novo Nordisk UK Research Foundation (G1001959) and Swedish Research Council. We acknowledge the OBB-NIHR Oxford Biomedical Research Centre and the British Heart Foundation (BHF) (RG/17/1/32663). Work performed at the MRC Epidemiology Unit was funded by the United Kingdom's Medical Research Council through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity