The Dark Side of the Electroweak Phase Transition

Recent data from cosmic ray experiments may be explained by a new GeV scale of physics. In addition the fine-tuning of supersymmetric models may be alleviated by new O(GeV) states into which the Higgs boson could decay. The presence of these new, light states can affect early universe cosmology. We explore the consequences of a light (~ GeV) scalar on the electroweak phase transition. We find that trilinear interactions between the light state and the Higgs can allow a first order electroweak phase transition and a Higgs mass consistent with experimental bounds, which may allow electroweak baryogenesis to explain the cosmological baryon asymmetry. We show, within the context of a specific supersymmetric model, how the physics responsible for the first order phase transition may also be responsible for the recent cosmic ray excesses of PAMELA, FERMI etc. We consider the production of gravity waves from this transition and the possible detectability at LISA and BBO

Immunoelectron Microscopic Evidence for Tetherin/BST2 as the Physical Bridge between HIV-1 Virions and the Plasma Membrane

Tetherin/BST2 was identified in 2008 as the cellular factor responsible for restricting HIV-1 replication at a very late stage in the lifecycle. Tetherin acts to retain virion particles on the plasma membrane after budding has been completed. Infected cells that express large amounts of tetherin display large strings of HIV virions that remain attached to the plasma membrane. Vpu is an HIV-1 accessory protein that specifically counteracts the restriction to virus release contributed by tetherin. Tetherin is an unusual Type II transmembrane protein that contains a GPI anchor at its C-terminus and is found in lipid rafts. The leading model for the mechanism of action of tetherin is that it functions as a direct physical tether bridging virions and the plasma membrane. However, evidence that tetherin functions as a physical tether has thus far been indirect. Here we demonstrate by biochemical and immunoelectron microscopic methods that endogenous tetherin is present on the viral particle and forms a bridge between virion particles and the plasma membrane. Endogenous tetherin was found on HIV particles that were released by partial proteolytic digestion. Immunoelectron microscopy performed on HIV-infected T cells demonstrated that tetherin forms an apparent physical link between virions and connects patches of virions to the plasma membrane. Linear filamentous strands that were highly enriched in tetherin bridged the space between some virions. We conclude that tetherin is the physical tether linking HIV-1 virions and the plasma membrane. The presence of filaments with which multiple molecules of tetherin interact in connecting virion particles is strongly suggested by the morphologic evidence

Analysis of physical pore space characteristics of two pyrolytic biochars and potential as microhabitat

Background and Aims Biochar amendment to soil is a promising practice of enhancing productivity of agricultural systems. The positive effects on crop are often attributed to a promotion of beneficial soil microorganisms while suppressing pathogens e.g. This study aims to determine the influence of biochar feedstock on (i) spontaneous and fungi inoculated microbial colonisation of biochar particles and (ii) physical pore space characteristics of native and fungi colonised biochar particles which impact microbial habitat quality. Methods Pyrolytic biochars from mixed woods and Miscanthus were investigated towards spontaneous colonisation by classical microbiological isolation, phylogenetic identification of bacterial and fungal strains, and microbial respiration analysis. Physical pore space characteristics of biochar particles were determined by X-ray μ-CT. Subsequent 3D image analysis included porosity, surface area, connectivities, and pore size distribution. Results Microorganisms isolated from Wood biochar were more abundant and proliferated faster than those from the Miscanthus biochar. All isolated bacteria belonged to gram-positive bacteria and were feedstock specific. Respiration analysis revealed higher microbial activity for Wood biochar after water and substrate amendment while basal respiration was on the same low level for both biochars. Differences in porosity and physical surface area were detected only in interaction with biochar-specific colonisation. Miscanthus biochar was shown to have higher connectivity values in surface, volume and transmission than Wood biochars as well as larger pores as observed by pore size distribution. Differences in physical properties between colonised and non-colonised particles were larger in Miscanthus biochar than in Wood biochar. Conclusions Vigorous colonisation was found on Wood biochar compared to Miscanthus biochar. This is contrasted by our findings from physical pore space analysis which suggests better habitat quality in Miscanthus biochar than in Wood biochar. We conclude that (i) the selected feedstocks display large differences in microbial habitat quality as well as physical pore space characteristics and (ii) physical description of biochars alone does not suffice for the reliable prediction of microbial habitat quality and recommend that physical and surface chemical data should be linked for this purpose

Antagonism of Tetherin Restriction of HIV-1 Release by Vpu Involves Binding and Sequestration of the Restriction Factor in a Perinuclear Compartment

The Vpu accessory protein promotes HIV-1 release by counteracting Tetherin/BST-2, an interferon-regulated restriction factor, which retains virions at the cell-surface. Recent reports proposed β-TrCP-dependent proteasomal and/or endo-lysosomal degradation of Tetherin as potential mechanisms by which Vpu could down-regulate Tetherin cell-surface expression and antagonize this restriction. In all of these studies, Tetherin degradation did not, however, entirely account for Vpu anti-Tetherin activity. Here, we show that Vpu can promote HIV-1 release without detectably affecting Tetherin steady-state levels or turnover, suggesting that Tetherin degradation may not be necessary and/or sufficient for Vpu anti-Tetherin activity. Even though Vpu did not enhance Tetherin internalization from the plasma membrane (PM), it did significantly slow-down the overall transport of the protein towards the cell-surface. Accordingly, Vpu expression caused a specific removal of cell-surface Tetherin and a re-localization of the residual pool of Tetherin in a perinuclear compartment that co-stained with the TGN marker TGN46 and Vpu itself. This re-localization of Tetherin was also observed with a Vpu mutant unable to recruit β-TrCP, suggesting that this activity is taking place independently from β-TrCP-mediated trafficking and/or degradation processes. We also show that Vpu co-immunoprecipitates with Tetherin and that this interaction involves the transmembrane domains of the two proteins. Importantly, this association was found to be critical for reducing cell-surface Tetherin expression, re-localizing the restriction factor in the TGN and promoting HIV-1 release. Overall, our results suggest that association of Vpu to Tetherin affects the outward trafficking and/or recycling of the restriction factor from the TGN and as a result promotes its sequestration away from the PM where productive HIV-1 assembly takes place. This mechanism of antagonism that results in TGN trapping is likely to be augmented by β-TrCP-dependent degradation, underlining the need for complementary and perhaps synergistic strategies to effectively counteract the powerful restrictive effects of human Tetherin

Polarity Changes in the Transmembrane Domain Core of HIV-1 Vpu Inhibits Its Anti-Tetherin Activity

Tetherin (BST-2/CD317) is an interferon-inducible antiviral protein that restricts the release of enveloped viruses from infected cells. The HIV-1 accessory protein Vpu can efficiently antagonize this restriction. In this study, we analyzed mutations of the transmembrane (TM) domain of Vpu, including deletions and substitutions, to delineate amino acids important for HIV-1 viral particle release and in interactions with tetherin. The mutants had similar subcellular localization patterns with that of wild-type Vpu and were functional with respect to CD4 downregulation. We showed that the hydrophobic binding surface for tetherin lies in the core of the Vpu TM domain. Three consecutive hydrophobic isoleucine residues in the middle region of the Vpu TM domain, I15, I16 and I17, were important for stabilizing the tetherin binding interface and determining its sensitivity to tetherin. Changing the polarity of the amino acids at these positions resulted in severe impairment of Vpu-induced tetherin targeting and antagonism. Taken together, these data reveal a model of specific hydrophobic interactions between Vpu and tetherin, which can be potentially targeted in the development of novel anti-HIV-1 drugs

HIV-2 interaction with cell coreceptors: amino acids within the V1/V2 region of viral envelope are determinant for CCR8, CCR5 and CXCR4 usage

© 2014 Santos-Costa et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Human immunodeficiency virus 1 and 2 (HIV-1 and HIV-2) use cellular receptors in distinct ways. Besides a more promiscuous usage of coreceptors by HIV-2 and a more frequent detection of CD4-independent HIV-2 isolates, we have previously identified two HIV-2 isolates (HIV-2MIC97 and HIV-2MJC97) that do not use the two major HIV coreceptors: CCR5 and CXCR4. All these features suggest that in HIV-2 the Env glycoprotein subunits may have a different structural organization enabling distinct - although probably less efficient - interactions with cellular receptors. Results: By infectivity assays using GHOST cell line expressing CD4 and CCR8 and blocking experiments using CCR8-specific ligand, I-309, we show that efficient replication of HIV-2MIC97 and HIV-2MJC97 requires the presence of CCR8 at plasma cell membrane. Additionally, we disclosed the determinants of chemokine receptor usage at the molecular level, and deciphered the amino acids involved in the usage of CCR8 (R8 phenotype) and in the switch from CCR8 to CCR5 or to CCR5/CXCR4 usage (R5 or R5X4 phenotype). The data obtained from site-directed mutagenesis clearly indicates that the main genetic determinants of coreceptor tropism are located within the V1/V2 region of Env surface glycoprotein of these two viruses. Conclusions: We conclude that a viral population able to use CCR8 and unable to infect CCR5 or CXCR4-positive cells, may exist in some HIV-2 infected individuals during an undefined time period, in the course of the asymptomatic stage of infection. This suggests that in vivo alternate molecules might contribute to HIV infection of natural target cells, at least under certain circumstances. Furthermore we provide direct and unequivocal evidence that the usage of CCR8 and the switch from R8 to R5 or R5X4 phenotype is determined by amino acids located in the base and tip of V1 and V2 loops of HIV-2 Env surface glycoprotein.This work was supported by grants from: Fundação para a Ciência e Tecnologia (FCT; PPCDT/SAU-IMI/55726/2004); Fundação para a Ciência e Tecnologia and Ministério da Saúde de Portugal (VIH/SAU/0006/2011); and from Gilead Sciences Portugal (Programa Gilead Génese).info:eu-repo/semantics/publishedVersio

The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide

Background: A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods: We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results: The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions: This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet

Associations between physical activity types and multi-domain cognitive decline in older adults from the Three-city cohort

Several studies suggest that physical activity improves cognitive functions and reduces cognitive decline, whereas others did not find any evidence of a neuroprotective effect. Furthermore, few cohort studies have analyzed the different physical activity types and particularly household activities. Our objective was to assess the association of two physical activity types with the decline in different cognitive domains in a large prospective cohort of community-dwelling older adults from the Three-city study. Physical activity (domestic/transportation activities and leisure/sport activities) was assessed with the Voorrips questionnaire, specific for older adults. Baseline sociodemographic and health history variables as well as cognitive performance data at baseline and during the 8-year follow-up (Mini-Mental State Examination, Benton Visual Retention Test, Trail Making Tests A and B, Isaac's Set Test and Free and Cued Selective Reminding Test) were also available. Associations between physical activity scores and cognitive decline in different domains were tested using minimally- and multi-adjusted linear mixed models. The analysis included 1697 participants without dementia at baseline and with at least one follow-up visit. At baseline, participants with higher sub-scores for the two physical activity types had better cognitive performances. Interaction with time showed that decline in some cognitive scores (Trail Making Test B and Isaac's Set Test) was significantly less pronounced in participants with higher household/transportation activity sub-scores. No significant effect over time was found for leisure/sport activities. This study shows that during an 8-year follow-up, executive functions and verbal fluency were better preserved in older adults who performed household/transportation activities at moderate to high level. Participation in domestic activities and using adapted transport means could allow older adults to maintain specific cognitive abilities