501 research outputs found
Interaction of the Host and Viral Genome and Their Influence on HIV Disease
The course of Human Immunodeficiency Virus type 1 (HIV) infection is a dynamic interplay in which both host and viral genetic variation, among other factors, influence disease susceptibility and rate of progression. HIV set-point viral load (spVL), a key indicator of HIV disease progression, has an estimated 30% of variance attributable to common heritable effects and roughly 70% attributable to environmental factors and/or additional non-genetic factors. Genome-wide genotyping and sequencing studies have allowed for large-scale association testing studying host and viral genetic variants associated with infection and disease progression. Host genomics of HIV infection has been studied predominantly in Caucasian populations consistently identifying human leukocyte antigen (HLA) genes and C-C motif chemokine receptor 5 as key factors of HIV susceptibility and progression. However, these studies don’t fully assess all classes of genetic variation (e.g., very rare polymorphisms, copy number variants etc.) and do not inform on non-European ancestry groups. Additionally, viral sequence variability has been demonstrated to influence disease progression independently of host genetic variation. Viral sequence variation can be attributed to the rapid evolution of the virus within the host due to the selective pressure of the host immune response. As the host immune system responds to the virus, e.g., through recognition of HIV antigens, the virus is able to mitigate this response by evolving HLA-specific escape mutations. Diversity of viral genotypes has also been correlated with moderate to strong effects on CD4+ T cell decline and some studies showing weak to no correlation with spVL. There is evidence to support these viral genetic factors being heritable between individuals and the evolution of these factors having important consequences in the genetic epidemiology of HIV infection on a population level. This review will discuss the host-pathogen interaction of HIV infection, explore the importance of host and viral genetics for a better understanding of pathogenesis and identify opportunities for additional genetic studies
Time-course changes associated with PA Lumbar Mobilizations on Lumbar and Hamstring Range of Motion:A Randomized Controlled Crossover Trial
Objective: We aimed to compare the post-intervention time-course changes in active knee extension (AKE) and active lumbar flexion (ALF) range of motion in response to unilateral posterior–anterior (UPA) mobilizations of the lumbar spine (L4/5 zygapophyseal).
Methods: Twenty-four asymptomatic participants (maleness: 0.58, age [mean ± standard deviation]: 32 ± 8 years, body mass index 25.9 ± 2.6 kg m2) were recruited to a fully controlled crossover trial. Following either the intervention (L4/5 zygapophyseal mobilizations) or control, participants immediately performed the AKE and ALF tests, which were also performed at baseline. Subsequent tests were made at intervals of 5, 10, 15, 20, 25, 30, 45 and 60 min.
Results: After adjustment for baseline (mean AKE: 37.2° from full extension, mean ALF: 14.37 cm), sex and age, UPA lumbar mobilizations had a most likely moderate effect on AKE (9.8° closer to full extension; ±1.9) and a likely moderate effect on ALF (1.34 cm; ±90% confidence limits 0.43). The magnitude of the AKE effect became most likely small 20-min posttreatment (5.3; ±1.7) and possibly small/possibly trivial 60-min posttreatment (2.1; ±1.4). For ALF, the magnitude of the effect became most likely small 15-min posttreatment (0.76; ±0.25), possibly small/possibly trivial 25-min posttreatment (0.38; ±0.18) and likely trivial 60-min posttreatment (0.26; ±1.8).
Discussion: UPA lumbar mobilizations increased lumbar Range of Motion and hamstring extensibility by a moderate magnitude, with the effect reducing after 10–20-min posttreatment. Clinicians should consider these time-course changes when applying UPA lumbar mobilizations
Artificial grass: a longitudinal study on ball roll and free pile height
Ball roll is seen as one of the first criterion which cause artificial grass pitches to fail performance standards. Previous research has demonstrated that the ball roll distance increased after a seven-year period. However, there is a lack of understanding in the mechanisms causing the ball roll distance to increase with time. During this study, the ball roll distance and free pile height were measured over a twelve-month period on an indoor pitch. The aim was to evaluate the early-life pitch performance and to determine if a correlation existed between ball roll distance and free pile height. The indoor environment protected the measurements from the confounding effects of wind and precipitation, providing a controlled environment in which to assess the effects of mechanical wear from player usage on both ball roll and free pile height.
There was a general trend for the ball roll distance to increase and the free pile height to reduce with time. There was a strong, negative correlation (R= -0.967) between ball roll distance and free pile height. The ball roll distance increased above the FIFA 2* limit within the first twelve months of pitch life, however intervening drag brushing the surface was found to reduce ball roll distance to within the requirements, signifying the importance of regular drag brushing. Significant spatial variation (P<0.001) existed in ball roll and free pile height between high use and low use areas of the pitch. The study provides strong evidence on the effects of free pile height on the ball roll distance, indicating that pitch owners need effective maintenance to ensure the carpet pile remains upright to maintain ball roll distance to meet performance standards
Understanding the effects of decompaction maintenance on the infill state and play performance of third-generation artificial grass pitches
Third generation artificial grass pitches have been observed to get harder over time. The maintenance technique of rubber infill decompaction is intended to help slow, or reverse, this process. At present, little is understood about either the science of the infill compaction process or the efficacy of decompaction maintenance. The objective of this study was to measure the changes in rubber infill net bulk density, force reduction (impact absorption) and vertical ball rebound under various levels of compactive effort in controlled laboratory-based testing. The assessments were repeated after the systems had been raked to simulate the decompaction maintenance techniques. These tests defined the limits of compaction (loose to maximally compacted) in terms of the change in rubber infill net bulk density, force reduction and vertical ball rebound. Site testing was also undertaken at four third generation pitches immediately pre and post decompaction, to determine the measurable effects in the less well controlled field environment. Rubber infill net bulk density was found to increase as compactive effort increased, resulting in increased hardness. Decompacting the surface was found to approximately fully reverse these effects. In comparison, the site measurements demonstrated similar but notably smaller magnitudes of change following the decompaction process suggesting that the field state pre and post decompaction did not reach the extremes obtained in the laboratory. The findings suggest that rubber infill net bulk density is an important parameter influencing the hardness of artificial grass and that decompactions can be an effective method to reverse compaction related hardness changes
Artificial grass: a longitudinal study on ball roll and free pile height
Ball roll is seen as one of the first criterion which cause artificial grass pitches to fail performance standards. Previous research has demonstrated that the ball roll distance increased after a seven-year period. However, there is a lack of understanding in the mechanisms causing the ball roll distance to increase with time. During this study, the ball roll distance and free pile height were measured over a twelve-month period on an indoor pitch. The aim was to evaluate the early-life pitch performance and to determine if a correlation existed between ball roll distance and free pile height. The indoor environment protected the measurements from the confounding effects of wind and precipitation, providing a controlled environment in which to assess the effects of mechanical wear from player usage on both ball roll and free pile height.
There was a general trend for the ball roll distance to increase and the free pile height to reduce with time. There was a strong, negative correlation (R= -0.967) between ball roll distance and free pile height. The ball roll distance increased above the FIFA 2* limit within the first twelve months of pitch life, however intervening drag brushing the surface was found to reduce ball roll distance to within the requirements, signifying the importance of regular drag brushing. Significant spatial variation (P<0.001) existed in ball roll and free pile height between high use and low use areas of the pitch. The study provides strong evidence on the effects of free pile height on the ball roll distance, indicating that pitch owners need effective maintenance to ensure the carpet pile remains upright to maintain ball roll distance to meet performance standards
HLA Class I and KIR Genes Do Not Protect Against HIV Type 1 Infection in Highly Exposed Uninfected Individuals With Hemophilia A
A recent genome-wide association study (GWAS) involving patients with hemophilia A who were exposed to but uninfected with human immunodeficiency virus type 1 (HIV-1) did not reveal genetic variants associated with resistance to HIV-1 infection, beyond homozygosity for CCR5-Δ32. Since variation in HLA class I and KIR genes is not well interrogated by standard GWAS techniques, we tested whether these 2 loci were involved in protection from HIV-1 infection in the same hemophilia cohort, using controls from the general population. Our data indicate that HLA class I alleles, presence or absence of KIR genes, and functionally relevant combinations of the HLA/KIR genotypes are not involved in resistance to parenterally transmitted HIV-1 infectio
HIV-1 Capture and Transmission by Dendritic Cells : The Role of Viral Glycolipids and the Cellular Receptor Siglec-1
Altres ajuts: Work in JMP group is supported by the Spanish AIDS network "Red Temática Cooperativa de Investigación en SIDA" (RD06/0006)Dendritic cells (DCs) are essential in order to combat invading viruses and trigger antiviral responses. Paradoxically, in the case of HIV-1, DCs might contribute to viral pathogenesis through trans -infection, a mechanism that promotes viral capture and transmission to target cells, especially after DC maturation. In this review, we highlight recent evidence identifying sialyllactose-containing gangliosides in the viral membrane and the cellular lectin Siglec-1 as critical determinants for HIV-1 capture and storage by mature DCs and for DC-mediated trans -infection of T cells. In contrast, DC-SIGN, long considered to be the main receptor for DC capture of HIV-1, plays a minor role in mature DC-mediated HIV-1 capture and trans -infection
Estimating the Respective Contributions of Human and Viral Genetic Variation to HIV Control
We evaluated the fraction of variation in HIV-1 set point viral load attributable to viral or human genetic factors by using joint host/pathogen genetic data from 541 HIV infected individuals. We show that viral genetic diversity explains 29% of the variation in viral load while host factors explain 8.4%. Using a joint model including both host and viral effects, we estimate a total of 30% heritability, indicating that most of the host effects are reflected in viral sequence variation
Disease-associated XMRV sequences are consistent with laboratory contamination.
BACKGROUND: Xenotropic murine leukaemia viruses (MLV-X) are endogenous gammaretroviruses that infect cells from many species, including humans. Xenotropic murine leukaemia virus-related virus (XMRV) is a retrovirus that has been the subject of intense debate since its detection in samples from humans with prostate cancer (PC) and chronic fatigue syndrome (CFS). Controversy has arisen from the failure of some studies to detect XMRV in PC or CFS patients and from inconsistent detection of XMRV in healthy controls. RESULTS: Here we demonstrate that Taqman PCR primers previously described as XMRV-specific can amplify common murine endogenous viral sequences from mouse suggesting that mouse DNA can contaminate patient samples and confound specific XMRV detection. To consider the provenance of XMRV we sequenced XMRV from the cell line 22Rv1, which is infected with an MLV-X that is indistinguishable from patient derived XMRV. Bayesian phylogenies clearly show that XMRV sequences reportedly derived from unlinked patients form a monophyletic clade with interspersed 22Rv1 clones (posterior probability >0.99). The cell line-derived sequences are ancestral to the patient-derived sequences (posterior probability >0.99). Furthermore, pol sequences apparently amplified from PC patient material (VP29 and VP184) are recombinants of XMRV and Moloney MLV (MoMLV) a virus with an envelope that lacks tropism for human cells. Considering the diversity of XMRV we show that the mean pairwise genetic distance among env and pol 22Rv1-derived sequences exceeds that of patient-associated sequences (Wilcoxon rank sum test: p = 0.005 and p < 0.001 for pol and env, respectively). Thus XMRV sequences acquire diversity in a cell line but not in patient samples. These observations are difficult to reconcile with the hypothesis that published XMRV sequences are related by a process of infectious transmission. CONCLUSIONS: We provide several independent lines of evidence that XMRV detected by sensitive PCR methods in patient samples is the likely result of PCR contamination with mouse DNA and that the described clones of XMRV arose from the tumour cell line 22Rv1, which was probably infected with XMRV during xenografting in mice. We propose that XMRV might not be a genuine human pathogen
Insights into the influence of solvent polarity on the crystallization of poly(ethylene oxide) spin-coated thin films via in situ grazing incidence wide-angle X-ray scattering
Controlling polymer thin-film morphology and crystallinity is crucial for a wide range of applications, particularly in thin-film organic electronic devices. In this work, the crystallization behavior of a model polymer, poly(ethylene oxide) (PEO), during spin-coating is studied. PEO films were spun-cast from solvents possessing different polarities (chloroform, THF, and methanol) and probed via in situ grazing incidence wide-angle X-ray scattering. The crystallization behavior was found to follow the solvent polarity order (where chloroform chloroform > methanol). When spun-cast from nonpolar chloroform, crystallization largely followed Avrami kinetics, resulting in the formation of morphologies comprising large spherulites. PEO solutions cast from more polar solvents (THF and methanol) do not form well-defined highly crystalline morphologies and are largely amorphous with the presence of small crystalline regions. The difference in morphological development of PEO spun-cast from polar solvents is attributed to clustering phenomena that inhibit polymer crystallization. This work highlights the importance of considering individual components of polymer solubility, rather than simple total solubility, when designing processing routes for the generation of morphologies with optimum crystallinities or morphologies
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