A Prominent Role for DC-SIGN+ Dendritic Cells in Initiation and Dissemination of Measles Virus Infection in Non-Human Primates

Measles virus (MV) is a highly contagious virus that is transmitted by aerosols. During systemic infection, CD150+T and B lymphocytes in blood and lymphoid tissues are the main cells infected by pathogenic MV. However, it is unclear which cell types are the primary targets for MV in the lungs and how the virus reaches the lymphoid tissues. In vitro studies have shown that dendritic cell (DC) C-type lectin DC-SIGN captures MV, leading to infection of DCs as well as transmission to lymphocytes. However, evidence of DC-SIGN-mediated transmission in vivo has not been established. Here we identified DC-SIGNhiDCs as first target cells in vivo and demonstrate that macaque DC-SIGN functions as an attachment receptor for MV. Notably, DC-SIGNhicells from macaque broncho-alveolar lavage and lymph nodes transmit MV to B lymphocytes, providing in vivo support for an important role for DCs in both initiation and dissemination of MV infection

The influence of different concentrations of flavanol chocolate bars under acute supplement conditions on exercise and performance

The purpose of this study was to assess the effects and acute dosage of different flavanol concentrations in a dark chocolate bar on physiological parameters during steady state (SS) and incremental exercise. In a double-blind, randomised, crossover study, 15 healthy participants with a mean ± SD age of 30 ± 7 years; stature 176.8 ± 8.6 cm and body mass 80.3 ± 8.4 kg supplemented with high flavanol (HF) (1060 mg), moderate flavanol (MF) (746 mg), low flavanol (LF) (406 mg), or a control (CON) (88 mg) chocolate bar (~ 34 g), 2 h prior to 40 min of SS cycling (80% gas-exchange threshold) followed by an incremental test to volitional fatigue. During the SS cycle oxygen consumption ([Formula: see text]), respiratory exchange ratio (RER) and heart rate (HR) were continuously monitored. Plasma samples were collected prior to commencing exercise to determine nitrate (NO ) and nitrite (NO ) levels under each condition. There was no observed effect between flavanol concentrations on [Formula: see text], RER, and HR during SS cycling (P > 0.05). [Formula: see text], peak power, HR peak, and RER peak also did not significantly differ between conditions (P > 0.05). There was a small trend for higher plasma NO levels following higher flavanol concentration; however, this did not reach statistical significance (P > 0.05). Acute supplementation with cocoa of differing flavanol concentrations does not appear to have any effect on exercise and performance. It is plausible that longer flavanol supplementation periods might have greater accumulative effects and thus may potentially elicit a larger effect

The gut microbiota of Colombians differs from that of Americans, Europeans and Asians

ABSTRACT: The composition of the gut microbiota has recently been associated with health and disease, particularly with obesity. Some studies suggested a higher proportion of Firmicutes and a lower proportion of Bacteroidetes in obese compared to lean people; others found discordant patterns. Most studies, however, focused on Americans or Europeans, giving a limited picture of the gut microbiome. To determine the generality of previous observations and expand our knowledge of the human gut microbiota, it is important to replicate studies in overlooked populations. Thus, we describe here, for the first time, the gut microbiota of Colombian adults via the pyrosequencing of the 16S ribosomal DNA (rDNA), comparing it with results obtained in Americans, Europeans, Japanese and South Koreans, and testing the generality of previous observations concerning changes in Firmicutes and Bacteroidetes with increasing body mass index (BMI). Results: We found that the composition of the gut microbiota of Colombians was significantly different from that of Americans, Europeans and Asians. The geographic origin of the population explained more variance in the composition of this bacterial community than BMI or gender. Concerning changes in Firmicutes and Bacteroidetes with obesity, in Colombians we found a tendency in Firmicutes to diminish with increasing BMI, whereas no change was observed in Bacteroidetes. A similar result was found in Americans. A more detailed inspection of the Colombian dataset revealed that five fiber-degrading bacteria, including Akkermansia, Dialister, Oscillospira, Ruminococcaceae and Clostridiales, became less abundant in obese subjects. Conclusion: We contributed data from unstudied Colombians that showed that the geographic origin of the studied population had a greater impact on the composition of the gut microbiota than BMI or gender. Any strategy aiming to modulate or control obesity via manipulation of this bacterial community should consider this effect

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand

Objective: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. Design: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. Methods: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. Results: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. Conclusion: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Stable transgenic C9orf72 zebrafish model key aspects of the ALS/FTD phenotype and reveal novel pathological features

A hexanucleotide repeat expansion (HRE) within the chromosome 9 open reading frame 72 (C9orf72) gene is the most prevalent cause of amyotrophic lateral sclerosis/fronto-temporal dementia (ALS/FTD). Current evidence suggests HREs induce neurodegeneration through accumulation of RNA foci and/or dipeptide repeat proteins (DPR). C9orf72 patients are known to have transactive response DNA binding protein 43 kDa (TDP-43) proteinopathy, but whether there is further cross over between C9orf72 pathology and the pathology of other ALS sub-types has yet to be revealed.To address this, we generated and characterised two zebrafish lines expressing C9orf72 HREs. We also characterised pathology in human C9orf72-ALS cases. In addition, we utilised a reporter construct that expresses DsRed under the control of a heat shock promoter, to screen for potential therapeutic compounds.Both zebrafish lines showed accumulation of RNA foci and DPR. Our C9-ALS/FTD zebrafish model is the first to recapitulate the motor deficits, cognitive impairment, muscle atrophy, motor neuron loss and mortality in early adulthood observed in human C9orf72-ALS/FTD. Furthermore, we identified that in zebrafish, human cell lines and human post-mortem tissue, C9orf72 expansions activate the heat shock response (HSR). Additionally, HSR activation correlated with disease progression in our C9-ALS/FTD zebrafish model. Lastly, we identified that the compound ivermectin, as well as riluzole, reduced HSR activation in both C9-ALS/FTD and SOD1 zebrafish models.Thus, our C9-ALS/FTD zebrafish model is a stable transgenic model which recapitulates key features of human C9orf72-ALS/FTD, and represents a powerful drug-discovery tool