Molecular Epidemiology of Early and Acute HIV Type 1 Infections in the United States Navy and Marine Corps, 2005–2010

The U.S. military represents a unique population within the human immunodeficiency virus 1 (HIV-1) pandemic. The last comprehensive study of HIV-1 in members of the U.S. Navy and Marine Corps (Sea Services) was completed in 2000, before large-scale combat operations were taking place. Here, we present molecular characterization of HIV-1 from 40 Sea Services personnel who were identified during their seroconversion window and initially classified as HIV-1 negative during screening. Protease/reverse transcriptase (pro/rt) and envelope (env) sequences were obtained from each member of the cohort. Phylogenetic analyses were carried out on these regions to determine relatedness within the cohort and calculate the most recent common ancestor for the related sequences. We identified 39 individuals infected with subtype B and one infected with CRF01_AE. Comparison of the pairwise genetic distance of Sea Service sequences and reference sequences in the env and pro/rt regions showed that five samples were part of molecular clusters, a group of two and a group of three, confirmed by single genome amplification. Real-time molecular monitoring of new HIV-1 acquisitions in the Sea Services may have a role in facilitating public health interventions at sites where related HIV-1 infections are identified

Molecular Epidemiology of Early and Acute HIV Type 1 Infections in the United States Navy and Marine Corps, 2005–2010

The U.S. military represents a unique population within the human immunodeficiency virus 1 (HIV-1) pandemic. The last comprehensive study of HIV-1 in members of the U.S. Navy and Marine Corps (Sea Services) was completed in 2000, before large-scale combat operations were taking place. Here, we present molecular characterization of HIV-1 from 40 Sea Services personnel who were identified during their seroconversion window and initially classified as HIV-1 negative during screening. Protease/reverse transcriptase (pro/rt) and envelope (env) sequences were obtained from each member of the cohort. Phylogenetic analyses were carried out on these regions to determine relatedness within the cohort and calculate the most recent common ancestor for the related sequences. We identified 39 individuals infected with subtype B and one infected with CRF01_AE. Comparison of the pairwise genetic distance of Sea Service sequences and reference sequences in the env and pro/rt regions showed that five samples were part of molecular clusters, a group of two and a group of three, confirmed by single genome amplification. Real-time molecular monitoring of new HIV-1 acquisitions in the Sea Services may have a role in facilitating public health interventions at sites where related HIV-1 infections are identified

HIV-1 genetic diversity and demographic characteristics in Bulgaria.

HIV-1 strain diversity in Bulgaria is extensive and includes contributions from nearly all major subtypes and the Circulating Recombinant Forms (CRF): 01_AE, 02_AG, and 05_DF. Prior to this study, HIV-1 sequence information from Bulgaria has been based solely on the pro-RT gene, which represent less than 15% of the viral genome. To further characterize HIV-1 in Bulgaria, assess participant risk behaviors, and strengthen knowledge of circulating strains in the region, the study "Genetic Subtypes of HIV-1 in Bulgaria (RV240)" was conducted. This study employed the real time-PCR based Multi-region Hybridization Assay (MHA) B/non-B and HIV-1 sequencing to survey 215 of the approximately 1100 known HIV-1 infected Bulgarian adults (2008-2009) and determine if they were infected with subtype B HIV-1. The results indicated a subtype B prevalence of 40% and demonstrate the application of the MHA B/non-B in an area containing broad HIV-1 strain diversity. Within the assessed risk behaviors, the proportion of subtype B infection was greatest in men who have sex with men and lowest among those with drug use risk factors. During this study, 15 near full-length genomes and 22 envelope sequences were isolated from study participants. Phylogenetic analysis shows the presence of subtypes A1, B, C, F1, and G, CRF01_AE, CRF02_AG, CRF05_DF, and one unique recombinant form (URF). These sequences also show the presence of two strain groups containing participants with similar risk factors. Previous studies in African and Asian cohorts have shown that co-circulation of multiple subtypes can lead to viral recombination within super-infected individuals and the emergence of new URFs. The low prevalence of URFs in the presence of high subtype diversity in this study, may be the result of successful infection prevention and control programs. Continued epidemiological monitoring and support of infection prevention programs will help maintain control of the HIV-1 epidemic in Bulgaria

Mitochondrial DNA sequence variation is associated with free-living activity energy expenditure in the elderly

The decline in activity energy expenditure underlies a range of age-associated pathological conditions, neuromuscular and neurological impairments, disability, and mortality. The majority (90%) of the energy needs of the human body are met by mitochondrial oxidative phosphorylation (OXPHOS). OXPHOS is dependent on the coordinated expression and interaction of genes encoded in the nuclear and mitochondrial genomes. We examined the role of mitochondrial genomic variation in free-living activity energy expenditure (AEE) and physical activity levels (PAL) by sequencing the entire (~16.5 kilobases) mtDNA from 138 Health, Aging, and Body Composition Study participants. Among the common mtDNA variants, the hypervariable region 2 m.185G>A variant was significantly associated with AEE (p=0.001) and PAL (p=0.0005) after adjustment for multiple comparisons. Several unique nonsynonymous variants were identified in the extremes of AEE with some occurring at highly conserved sites predicted to affect protein structure and function. Of interest is the p.T194M, CytB substitution in the lower extreme of AEE occurring at a residue in the Qi site of complex III. Among participants with low activity levels, the burden of singleton variants was 30% higher across the entire mtDNA and OXPHOS complex I when compared to those having moderate to high activity levels. A significant pooled variant association across the hypervariable 2 region was observed for AEE and PAL. These results suggest that mtDNA variation is associated with free-living AEE in older persons and may generate new hypotheses by which specific mtDNA complexes, genes, and variants may contribute to the maintenance of activity levels in late life

Systems Toxicology: From Basic Research to Risk Assessment

[Image: see text] Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment

Search for diphoton events with large missing transverse momentum in 1 fb(-1) of 7 TeV proton-proton collision data with the ATLAS detector ATLAS Collaboration

A search for diphoton events with large missing transverse momentum has been performed using 1.07 fb -1 of proton-proton collision data at s=7 TeV recorded with the ATLAS detector. No excess of events was observed above the Standard Model prediction and 95% Confidence Level (CL) upper limits are set on the production cross section for new physics. The limits depend on each model parameter space and vary as follows: Λ<(22-129) fb in the context of a generalised model of gauge-mediated supersymmetry breaking (GGM) with a bino-like lightest neutralino, σ<(27-91) fb in the context of a minimal model of gauge-mediated supersymmetry breaking (SPS8), and σ<(15-27) fb in the context of a specific model with one universal extra dimension (UED). A 95% CL lower limit of 805 GeV, for bino masses above 50 GeV, is set on the GGM gluino mass. Lower limits of 145 TeV and 1.23 TeV are set on the SPS8 breaking scale Λ and on the UED compactification scale 1/R, respectively. These limits provide the most stringent tests of these models to date. © 2012 CERN

Search for diphoton events with large missing transverse momentum in 1 fb^-1 of 7 TeV proton–proton collision data with the ATLAS detector

A search for diphoton events with large missing transverse momentum has been performed using 1.07 fb−1of proton–proton collision data at √s=7  TeV recorded with the ATLAS detector. No excess of events was observed above the Standard Model prediction and 95% Confidence Level (CL) upper limits are set on the production cross section for new physics. The limits depend on each model parameter space and vary as follows: σ<(22–129) fb in the context of a generalised model of gauge-mediated supersymmetry breaking (GGM) with a bino-like lightest neutralino, σ<(27–91) fb in the context of a minimal model of gauge-mediated supersymmetry breaking (SPS8), and σ< (15–27) fb in the context of a specific model with one universal extra dimension (UED). A 95% CL lower limit of 805 GeV, for bino masses above 50 GeV, is set on the GGM gluino mass. Lower limits of 145 TeV and 1.23 TeV are set on the SPS8 breaking scale ∧ and on the UED compactification scale 1/R, respectively. These limits provide the most stringent tests of these models to date

Search for diphoton events with large missing transverse momentum in 1 fb(-1) of 7 TeV proton-proton collision data with the ATLAS detector ATLAS Collaboration

A search for diphoton events with large missing transverse momentum has been performed using 1.07 fb(-1) of proton-proton collision data at root s = 7 TeV recorded with the ATLAS detector. No excess of events was observed above the Standard Model prediction and 95% Confidence Level (CL) upper limits are set on the production cross section for new physics. The limits depend on each model parameter space and vary as follows: sigma < (22-129) fb in the context of a generalised model of gauge-mediated supersymmetry breaking (GGM) with a bino-like lightest neutralino, sigma < (27-91) fb in the context of a minimal model of gauge-mediated supersymmetry breaking (SPS8), and sigma < (15-27) fb in the context of a specific model with one universal extra dimension (UED). A 95% CL lower limit of 805 GeV, for bino masses above 50 GeV, is set on the GGM gluino mass. Lower limits of 145 TeV and 1.23 TeV are set on the SPS8 breaking scale Lambda and on the UED compactification scale 1/R, respectively. These limits provide the most stringent tests of these models to date. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved. RI Sivoklokov, Sergey/D-8150-2012; Li, Xuefei/C-3861-2012; Smirnov, Sergei/F-1014-2011; Gladilin, Leonid/B-5226-2011; Barreiro, Fernando/D-9808-2012; Prokoshin, Fedor/E-2795-2012; Fazio, Salvatore /G-5156-2010; Orlov, Ilya/E-6611-2012; Doyle, Anthony/C-5889-2009; Alexa, Calin/F-6345-2010; Moorhead, Gareth/B-6634-2009; Livan, Michele/D-7531-2012; Takai, Helio/C-3301-2012; Petrucci, Fabrizio/G-8348-2012; Jones, Roger/H-5578-2011; Fabbri, Laura/H-3442-2012; Kurashige, Hisaya/H-4916-2012; Villa, Mauro/C-9883-2009; Delmastro, Marco/I-5599-201

Search for diphoton events with large missing transverse momentum in 1 fb(-1) of 7 TeV proton-proton collision data with the ATLAS detector ATLAS Collaboration

A search for diphoton events with large missing transverse momentum has been performed using 1.07 fb(-1) of proton-proton collision data at root s = 7 TeV recorded with the ATLAS detector. No excess of events was observed above the Standard Model prediction and 95% Confidence Level (CL) upper limits are set on the production cross section for new physics. The limits depend on each model parameter space and vary as follows: sigma < (22-129) fb in the context of a generalised model of gauge-mediated supersymmetry breaking (GGM) with a bino-like lightest neutralino, sigma < (27-91) fb in the context of a minimal model of gauge-mediated supersymmetry breaking (SPS8), and sigma < (15-27) fb in the context of a specific model with one universal extra dimension (UED). A 95% CL lower limit of 805 GeV, for bino masses above 50 GeV, is set on the GGM gluino mass. Lower limits of 145 TeV and 1.23 TeV are set on the SPS8 breaking scale Lambda and on the UED compactification scale 1/R, respectively. These limits provide the most stringent tests of these models to date. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved