3,015 research outputs found

    Interactions in vivo between the Vif protein of HIV-1 and the precursor (Pr55GAG) of the virion nucleocapsid proteins

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    The abnormality of viral core structure seen in vif-defective HIV-1 grown in PBMCs has suggested a role for Vif in viral morphogenesis. Using an in vivo mammalian two-hybrid assay, the interaction between Vif and the precursor (Pr55GAG) of the virion nucleocapsid proteins has been analysed. This revealed the amino-terminal (aa 1–22) and central (aa 70–100) regions of Vif to be essential for its interaction with Pr55GAG, but deletion of the carboxy-terminal (aa 158–192) region of the protein had only a minor effect on its interaction. Initial deletion studies carried out on Pr55GAG showed that a 35-amino-acid region of the protein bridging the MA(p17)–CA(p24) junction was essential for its ability to interact with Vif. Site-directed mutagenesis of a conserved tryptophan (Trp21) near the amino terminus of Vif showed it to be important for the interaction with Pr55GAG. By contrast, mutagenesis of the highly conserved YLAL residues forming part of the BC-box motif, shown to be important in Vif promoting degradation of APOBEC3G/3F, had little or no effect on the Vif–Pr55GAG interaction

    Gains in awareness, ownership and use of insecticide-treated nets in Nigeria, Senegal, Uganda and Zambia

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    Abstract Background In April 2000, the Roll Back Malaria (RBM) "Abuja Summit" set a target of having at least 60% of pregnant women and children under five use insecticide-treated nets (ITNs). Thereafter, programmes were implemented to create demand, reduce taxes and tariffs, spur the commercial market, and reach vulnerable populations with subsidized ITNs. Using national ITN monitoring data from the USAID-sponsored AED/NetMark project, this article examines the extent to which these activities were successful in increasing awareness, ownership, and use of nets and ITNs. Methods A series of surveys with standardized sampling and measurement methods was used to compare four countries at two points in time. Surveys were conducted in 2000 and again in 2004 (Nigeria, Senegal, Zambia) or 2006 (Uganda). They contained questions permitting classification of each net as untreated, ever-treated or currently-treated (an ITN). Household members as well as nets owned were enumerated so that households, household members, and nets could be used as units of analysis. Several measures of net/ITN ownership, plus RBM ITN use indicators, were calculated. The results show the impact of ITN activities before the launch of massive free net distribution programmes. Results In 2000, treated nets were just being introduced to the public, but four to six years later the awareness of ITNs was nearly universal in all countries but Nigeria, where awareness increased from 7% to 60%. By any measure, there were large increases in ownership of nets, especially treated nets, in all countries. All countries but Nigeria made commensurate gains in the proportion of under-fives sleeping under a net/ITN, and in all countries the proportion of pregnant women sleeping under a net/ITN increased greatly. Conclusion A mix of demand creation, a strengthened commercial sector, reduced taxes and tariffs, and programmes making ITNs available at reduced prices resulted in impressive gains in awareness, ownership, and use of nets and ITNs in Nigeria, Senegal, Zambia, and Uganda between 2000 and 2004–2006. None of the countries reached the ambitious Abuja targets for ITN use, but they made substantial progress towards them.</p

    Evidence for B cell exhaustion in chronic graft-versus-host disease

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    Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies support a role for B cells in the pathogenesis of cGvHD. In this study, we report the presence of an expanded population of CD19+CD21− B cells with features of exhaustion in the peripheral blood of patients with cGvHD. CD21− B cells were significantly increased in patients with active cGvHD compared to patients without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%, respectively; p < 0.01). Compared with naïve (CD27−CD21+) and classical memory (CD27+CD21+) B cells, CD19+CD21− B cells in cGvHD were CD10 negative, CD27 negative and CD20hi, and exhibited features of exhaustion, including increased expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and altered expression of chemokine and adhesion molecules such as CD11c, CXCR3, CCR7, and CD62L. Moreover, CD21− B cells in cGvHD patients were functionally exhausted and displayed poor proliferative response and calcium mobilization in response to B-cell receptor triggering and CD40 ligation. Finally, the frequencies of circulating CD21− B cells correlated with cGvHD severity in patients after HSCT. Our study further characterizes B cells in chronic cGVHD and supports the use of CD21−CD27−CD10− B cell frequencies as a biomarker of disease severity

    Controlling Cherenkov angles with resonance transition radiation

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    Cherenkov radiation provides a valuable way to identify high energy particles in a wide momentum range, through the relation between the particle velocity and the Cherenkov angle. However, since the Cherenkov angle depends only on material's permittivity, the material unavoidably sets a fundamental limit to the momentum coverage and sensitivity of Cherenkov detectors. For example, Ring Imaging Cherenkov detectors must employ materials transparent to the frequency of interest as well as possessing permittivities close to unity to identify particles in the multi GeV range, and thus are often limited to large gas chambers. It would be extremely important albeit challenging to lift this fundamental limit and control Cherenkov angles as preferred. Here we propose a new mechanism that uses constructive interference of resonance transition radiation from photonic crystals to generate both forward and backward Cherenkov radiation. This mechanism can control Cherenkov angles in a flexible way with high sensitivity to any desired range of velocities. Photonic crystals thus overcome the severe material limit for Cherenkov detectors, enabling the use of transparent materials with arbitrary values of permittivity, and provide a promising option suited for identification of particles at high energy with enhanced sensitivity.Comment: There are 16 pages and 4 figures for the manuscript. Supplementary information with 18 pages and 5 figures, appended at the end of the file with the manuscript. Source files in Word format converted to PDF. Submitted to Nature Physic

    Psychophysiological effects of massage-myofascial release after exercise: a randomized sham-control study

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    This is a copy of an article published in the Journal of Alternative and Complementary Medicine © 2008 Mary Ann Liebert, Inc.; Journal of Alternative and Complementary Medicine is available online at: http://online.liebertpub.com.Objective: The aim of this study was to evaluate the effect of massage on neuromuscular recruitment, mood state, and mechanical nociceptive threshold (MNT) after high-intensity exercise. Design: This was a prospective randomized clinical trial using between-groups design. Setting: The study was conducted at a university-based sports medicine clinic. Participants: Sixty-two (62) healthy active students age 18–26 participated. Interventions: Participants, randomized into two groups, performed three 30-second Wingate tests and immediately received whole-body massage-myofascial induction or placebo (sham ultrasound/magnetotherapy) treatment. The duration (40 minutes), position, and therapist were the same for both treatments. Main outcome measures: Dependent variables were surface electromyography (sEMG) of quadriceps, profile of mood states (POMS) and mechanical nociceptive threshold (MNT) of trapezius and masseter muscles. These data were assessed at baseline and after exercise and recovery periods. Results: Generalized estimating equations models were performed on dependent variables to assess differences between groups. Significant differences were found in effects of treatment on sEMG of Vastus Medialis (VM) (p 0.02) and vigor subscale (p 0.04). After the recovery period, there was a significant decrease in electromyographic (EMG) activity of VM (p 0.02) in the myofascial-release group versus a nonsignificant increase in the placebo group (p 0.32), and a decrease in vigor (p 0.01) in the massage group versus no change in the placebo group (p 0.86). Conclusions: Massage reduces EMG amplitude and vigor when applied as a passive recovery technique after a high-intensity exercise protocol. Massage may induce a transient loss of muscle strength or a change in the muscle fiber tension–length relationship, influenced by alterations of muscle function and a psychological state of relaxation.The trial was funded by a research project grant (11/UPB10/06) from the Spanish Higher Sports Council

    Hospitalization due to varicella in the Netherlands

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    <p>Abstract</p> <p>Background</p> <p>In the Netherlands, incidence of physician's consultations and hospitalizations for varicella is low compared to other countries. Better knowledge about the severity of varicella among Dutch hospitalized patients is needed. Therefore, a medical record research was conducted among hospitalized patients with diagnosis varicella.</p> <p>Methods</p> <p>Hospital admissions due to varicella in 2003-2006 were obtained from the National Medical Register. Retrospectively, additional data were retrieved from the medical record of patients hospitalized with varicella in 23 Dutch hospitals using a standardized form. Analyses were performed using descriptive statistics.</p> <p>Results</p> <p>The study population (N = 296) was representative for all varicella admissions in the Netherlands (N = 1,658) regarding age, sex, duration of admission and type of diagnosis. Complications were recorded in 76% of the patients (37% had at least one relatively severe complication). Bacterial super infections of skin lesions (28%), (imminent) dehydration (19%), febrile convulsions (7%), pneumonia (7%) and gastroenteritis (7%) were most frequently reported. No varicella-related death occurred within the study population and 3% of the patients had serious rest symptoms.</p> <p>Conclusions</p> <p>It is not likely that the severity of varicella among hospitalized patients in the Netherlands differs from other countries. A considerable part of the varicella complications among hospitalized patients was rather moderate and can be treated effectively, although in a third of the hospitalized cases with complications, severe complications occurred. These data are relevant in the decision-making process regarding whether or not to introduce routine varicella vaccination in the Netherlands.</p

    Effects of Male Hypogonadism on Regional Adipose Tissue Fatty Acid Storage and Lipogenic Proteins

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    Testosterone has long been known to affect body fat distribution, although the underlying mechanisms remain elusive. We investigated the effects of chronic hypogonadism in men on adipose tissue fatty acid (FA) storage and FA storage factors. Twelve men with chronic hypogonadism and 13 control men matched for age and body composition: 1) underwent measures of body composition with dual energy x-ray absorptiometry and an abdominal CT scan; 2) consumed an experimental meal containing [3H]triolein to determine the fate of meal FA (biopsy-measured adipose storage vs. oxidation); 3) received infusions of [U-13C]palmitate and [1-14C]palmitate to measure rates of direct free (F)FA storage (adipose biopsies). Adipose tissue lipoprotein lipase, acyl-CoA synthetase (ACS), and diacylglycerol acetyl-transferase (DGAT) activities, as well as, CD36 content were measured to understand the mechanism by which alterations in fat storage occur in response to testosterone deficiency. Results of the study showed that hypogonadal men stored a greater proportion of both dietary FA and FFA in lower body subcutaneous fat than did eugonadal men (both p<0.05). Femoral adipose tissue ACS activity was significantly greater in hypogonadal than eugonadal men, whereas CD36 and DGAT were not different between the two groups. The relationships between these proteins and FA storage varied somewhat between the two groups. We conclude that chronic effects of testosterone deficiency has effects on leg adipose tissue ACS activity which may relate to greater lower body FA storage. These results provide further insight into the role of androgens in body fat distribution and adipose tissue metabolism in humans
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