Siglec receptors impact mammalian lifespan by modulating oxidative stress.

Aging is a multifactorial process that includes the lifelong accumulation of molecular damage, leading to age-related frailty, disability and disease, and eventually death. In this study, we report evidence of a significant correlation between the number of genes encoding the immunomodulatory CD33-related sialic acid-binding immunoglobulin-like receptors (CD33rSiglecs) and maximum lifespan in mammals. In keeping with this, we show that mice lacking Siglec-E, the main member of the CD33rSiglec family, exhibit reduced survival. Removal of Siglec-E causes the development of exaggerated signs of aging at the molecular, structural, and cognitive level. We found that accelerated aging was related both to an unbalanced ROS metabolism, and to a secondary impairment in detoxification of reactive molecules, ultimately leading to increased damage to cellular DNA, proteins, and lipids. Taken together, our data suggest that CD33rSiglecs co-evolved in mammals to achieve a better management of oxidative stress during inflammation, which in turn reduces molecular damage and extends lifespan

The Earth Microbiome Project: Meeting report of the "1 EMP meeting on sample selection and acquisition" at Argonne National Laboratory October 6 2010.

This report details the outcome the first meeting of the Earth Microbiome Project to discuss sample selection and acquisition. The meeting, held at the Argonne National Laboratory on Wednesday October 6(th) 2010, focused on discussion of how to prioritize environmental samples for sequencing and metagenomic analysis as part of the global effort of the EMP to systematically determine the functional and phylogenetic diversity of microbial communities across the world

Ideal MHD theory of low-frequency Alfven waves in the H-1 Heliac

A part analytical, part numerical ideal MHD analysis of low-frequency Alfven wave physics in the H-1 stellarator is given. The three-dimensional, compressible ideal spectrum for H-1 is presented and it is found that despite the low beta (approx. 10^-4) of H-1 plasmas, significant Alfven-acoustic interactions occur at low frequencies. Several quasi-discrete modes are found with the three-dimensional linearised ideal MHD eigenmode solver CAS3D, including beta-induced Alfven eigenmode (BAE)- type modes in beta-induced gaps. The strongly shaped, low-aspect ratio magnetic geometry of H-1 causes CAS3D convergence difficulties requiring the inclusion of many Fourier harmonics for the parallel component of the fluid displacement eigenvector even for shear wave motions. The highest beta-induced gap reproduces large parts of the observed configurational frequency dependencies in the presence of hollow temperature profiles

Connecting the cosmic infrared background to the X-ray background

We estimate the contribution of AGNs and of their host galaxies to the infrared background. We use the luminosity function and evolution of AGNs recently determined by the hard X-ray surveys, and new Spectral Energy Distributions connecting the X-ray and the infrared emission, divided in intervals of absorption. These two ingredients allow us to determine the contribution of AGNs to the infrared background by using mostly observed quantities, with only minor assumptions. We obtain that AGN emission contributes little to the infrared background ($<$5% over most of the infrared bands), implying that the latter is dominated by star formation. However, AGN host galaxies may contribute significantly to the infrared background, and more specifically 10--20% in the 1--20$\mu$m range and $\sim$5% at $\lambda<60\mu m$. We also give the contribution of AGNs and of their host galaxies to the source number counts in various infrared bands, focusing on those which will be observed with Spitzer. We also report a significant discrepancy between the expected contribution of AGN hosts to the submm background and bright submm number counts with the observational constraints. We discuss the causes and implications of this discrepancy and the possible effects on the Spitzer far-IR bands.Comment: to appear in MNRAS, replaced with accepted version, paper shortened, results unchange

An elastoplastic framework for granular materials becoming cohesive through mechanical densification. Part I - small strain formulation

Mechanical densification of granular bodies is a process in which a loose material becomes increasingly cohesive as the applied pressure increases. A constitutive description of this process faces the formidable problem that granular and dense materials have completely different mechanical behaviours (nonlinear elastic properties, yield limit, plastic flow and hardening laws), which must both be, in a sense, included in the formulation. A treatment of this problem is provided here, so that a new phenomenological, elastoplastic constitutive model is formulated, calibrated by experimental data, implemented and tested, that is capable of describing the transition between granular and fully dense states of a given material. The formulation involves a novel use of elastoplastic coupling to describe the dependence of cohesion and elastic properties on the plastic strain. The treatment falls within small strain theory, which is thought to be appropriate in several situations; however, a generalization of the model to large strain is provided in Part II of this paper.Comment: 42 pages, 27 figure

Human Immunodeficiency Virus Type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains

BACKGROUND: The Nef protein of Human Immunodeficiency Viruses optimizes viral spread in the infected host by manipulating cellular transport and signal transduction machineries. Nef also boosts the infectivity of HIV particles by an unknown mechanism. Recent studies suggested a correlation between the association of Nef with lipid raft microdomains and its positive effects on virion infectivity. Furthermore, the lipidome analysis of HIV-1 particles revealed a marked enrichment of classical raft lipids and thus identified HIV-1 virions as an example for naturally occurring membrane microdomains. Since Nef modulates the protein composition and function of membrane microdomains we tested here if Nef also has the propensity to alter microdomain lipid composition. RESULTS: Quantitative mass spectrometric lipidome analysis of highly purified HIV-1 particles revealed that the presence of Nef during virus production from T lymphocytes enforced their raft character via a significant reduction of polyunsaturated phosphatidylcholine species and a specific enrichment of sphingomyelin. In contrast, Nef did not significantly affect virion levels of phosphoglycerolipids or cholesterol. The observed alterations in virion lipid composition were insufficient to mediate Nef's effect on particle infectivity and Nef augmented virion infectivity independently of whether virus entry was targeted to or excluded from membrane microdomains. However, altered lipid compositions similar to those observed in virions were also detected in detergent-resistant membrane preparations of virus producing cells. CONCLUSION: Nef alters not only the proteome but also the lipid composition of host cell microdomains. This novel activity represents a previously unrecognized mechanism by which Nef could manipulate HIV-1 target cells to facilitate virus propagation in vivo

Bioclimatic envelope models predict a decrease in tropical forest carbon stocks with climate change in Madagascar

Recent studies have underlined the importance of climatic variables in determining tree height and biomass in tropical forests. Nonetheless, the effects of climate on tropical forest carbon stocks remain uncertain. In particular, the application of process-based dynamic global vegetation models has led to contrasting conclusions regarding the potential impact of climate change on tropical forest carbon storage. Using a correlative approach based on a bioclimatic envelope model and data from 1771 forest plots inventoried during the period 1996–2013 in Madagascar over a large climatic gradient, we show that temperature seasonality, annual precipitation and mean annual temperature are key variables in determining forest above-ground carbon density. Taking into account the explicative climate variables, we obtained an accurate (R2 = 70% and RMSE = 40 Mg ha−1) forest carbon map for Madagascar at 250 m resolution for the year 2010. This national map was more accurate than previously published global carbon maps (R2 ≤ 26% and RMSE ≥ 63 Mg ha−1). Combining our model with the climatic projections for Madagascar from 7 IPCC CMIP5 global climate models following the RCP 8.5, we forecast an average forest carbon stock loss of 17% (range: 7–24%) by the year 2080. For comparison, a spatially homogeneous deforestation of 0.5% per year on the same period would lead to a loss of 30% of the forest carbon stock. Synthesis. Our study shows that climate change is likely to induce a decrease in tropical forest carbon stocks. This loss could be due to a decrease in the average tree size and to shifts in tree species distribution, with the selection of small-statured species. In Madagascar, climate-induced carbon emissions might be, at least, of the same order of magnitude as emissions associated with anthropogenic deforestation

Comparative genomics of Toll-like receptor signalling in five species

<p>Abstract</p> <p>Background</p> <p>Over the last decade, several studies have identified quantitative trait loci (QTL) affecting variation of immune related traits in mammals. Recent studies in humans and mice suggest that part of this variation may be caused by polymorphisms in genes involved in Toll-like receptor (TLR) signalling. In this project, we used a comparative approach to investigate the importance of TLR-related genes in comparison with other immunologically relevant genes for resistance traits in five species by associating their genomic location with previously published immune-related QTL regions.</p> <p>Results</p> <p>We report the genomic localisation of <it>TLR1-10 </it>and ten associated signalling molecules in sheep and pig using <it>in-silico </it>and/or radiation hybrid (RH) mapping techniques and compare their positions with their annotated homologues in the human, cattle and mouse whole genome sequences. We also report medium-density RH maps for porcine chromosomes 8 and 13. A comparative analysis of the positions of previously published relevant QTLs allowed the identification of homologous regions that are associated with similar health traits in several species and which contain TLR related and other immunologically relevant genes. Additional evidence was gathered by examining relevant gene expression and association studies.</p> <p>Conclusion</p> <p>This comparative genomic approach identified eight genes as potentially causative genes for variations of health related traits. These include susceptibility to clinical mastitis in dairy cattle, general disease resistance in sheep, cattle, humans and mice, and tolerance to protozoan infection in cattle and mice. Four TLR-related genes (<it>TLR1</it>, <it>6</it>, <it>MyD88</it>, <it>IRF3</it>) appear to be the most likely candidate genes underlying QTL regions which control the resistance to the same or similar pathogens in several species. Further studies are required to investigate the potential role of polymorphisms within these genes.</p

Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle

AbstractFarm animals remain at risk of endemic, exotic and newly emerging viruses. Vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. A complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. However, identification of the causal polymorphisms is not straightforward as it generally requires large numbers of animals with linked phenotypes and genotypes. Investigation of genes underlying complex traits such as resistance or response to viral pathogens requires several genetic approaches including candidate genes deduced from knowledge about the cellular pathways leading to protection or pathology, or unbiased whole genome scans using markers spread across the genome.Evidence for host genetic variation exists for a number of viral diseases in cattle including bovine respiratory disease and anecdotally, foot and mouth disease virus (FMDV). We immunised and vaccinated a cattle cross herd with a 40-mer peptide derived from FMDV and a vaccine against bovine respiratory syncytial virus (BRSV). Genetic variation has been quantified. A candidate gene approach has grouped high and low antibody and T cell responders by common motifs in the peptide binding pockets of the bovine major histocompatibility complex (BoLA) DRB3 gene. This suggests that vaccines with a minimal number of epitopes that are recognised by most cattle could be designed. Whole genome scans using microsatellite and single nucleotide polymorphism (SNP) markers has revealed many novel quantitative trait loci (QTL) and SNP markers controlling both humoral and cell-mediated immunity, some of which are in genes of known immunological relevance including the toll-like receptors (TLRs).The sequencing, assembly and annotation of livestock genomes and is continuing apace. In addition, provision of high-density SNP chips should make it possible to link phenotypes with genotypes in field populations without the need for structured populations or pedigree information. This will hopefully enable fine mapping of QTL and ultimate identification of the causal gene(s). The research could lead to selection of animals that are more resistant to disease and new ways to improve vaccine efficacy