Treadmill exercise within lower body negative pressure protects leg lean tissue mass and extensor strength and endurance during bed rest.

Leg muscle mass and strength are decreased during reduced activity and non-weight-bearing conditions such as bed rest (BR) and spaceflight. Supine treadmill exercise within lower body negative pressure (LBNPEX) provides full-body weight loading during BR and may prevent muscle deconditioning. We hypothesized that a 40-min interval exercise protocol performed against LBNPEX 6 days week(-1) would attenuate losses in leg lean mass (LLM), strength, and endurance during 6° head-down tilt BR, with similar benefits for men and women. Fifteen pairs of healthy monozygous twins (8 male and 7 female pairs) completed 30 days of BR with one sibling of each twin pair assigned randomly as the non-exercise control (CON) and the other twin as the exercise subject (EX). Before and after BR, LLM and isokinetic leg strength and endurance were measured. Mean knee and ankle extensor and flexor strength and endurance and LLM decreased from pre- to post-BR in the male CON subjects (P < 0.01), but knee extensor strength and endurance, ankle extensor strength, and LLM were maintained in the male EX subjects. In contrast, no pre- to post-BR changes were significant in the female subjects, either CON or EX, likely due to their lower pre-BR values. Importantly, the LBNPEX countermeasure prevents or attenuates declines in LLM as well as extensor leg strength and endurance. Individuals who are stronger, have higher levels of muscular endurance, and/or have greater LLM are likely to experience greater losses during BR than those who are less fit

Staphylococcus aureus toxin suppresses antigen-specific T cell responses

Staphylococcus aureus remains a leading cause of human infection. These infections frequently recur when the skin is a primary site of infection, especially in infants and children. In contrast, invasive staphylococcal disease is less commonly associated with reinfection, suggesting that tissue-specific mechanisms govern the development of immunity. Knowledge of how S. aureus manipulates protective immunity has been hampered by a lack of antigen-specific models to interrogate the T cell response. Using a chicken egg OVA-expressing S. aureus strain to analyze OVA-specific T cell responses, we demonstrated that primary skin infection was associated with impaired development of T cell memory. Conversely, invasive infection induced antigen-specific memory and protected against reinfection. This defect in adaptive immunity following skin infection was associated with a loss of DCs, attributable to S. aureus α-toxin (Hla) expression. Gene- and immunization-based approaches to protect against Hla during skin infection restored the T cell response. Within the human population, exposure to α-toxin through skin infection may modulate the establishment of T cell-mediated immunity, adversely affecting long-term protection. These studies prompt consideration that vaccination targeting S. aureus may be most effective if delivered prior to initial contact with the organism

Systèmes de soutien des réseaux sociaux scientifiques : Une exploration qualitative des catalyseurs et des obstacles aux nouvelles études en médecine universitaire

Introduction: As academia begins to incorporate modern communication technologies into its scholarly structures, there are both enablers and barriers which foster academics’ uptake of these innovations. Those who are early adopters of academic social media - whether it be for education, research-related networking, or knowledge translation - may therefore be best positioned to highlight both enablers and barriers within their work environments. Methods: The authors conducted a constructivist grounded theory study to discern what prominent practitioners of academic social media (e.g. Twitter) have encountered in their careers. Participants were recruited via a snowball sampling technique and invited to participate in semi-structured interviews. Three investigators engaged in constant comparative analysis of incoming transcripts. To enhance rigour, we conducted an audit of the analysis and a participant member check. Results: Seventeen emerging influencers in the field of academic social media were recruited. After axial coding, the 30 enablers and 21 barriers to academic social media use were mapped to three spheres of influence: personal, institutional, and virtual. The investigators propose a framework that organizes these enablers and barriers around a tipping point where sustainability becomes possible. Conclusions: Multiple enablers and barriers were described to influence social media users within academic medicine. By organizing these facets into a personal, institutional, and virtual framework along a spectrum, we can begin to understand the underlying structures that potentiate the academic ecosystems in which social media and similar innovations may flourish.Introduction : Alors que le milieu universitaire commence à intégrer les technologies de communication modernes dans ses structures d’enseignement, il existe à la fois des facteurs favorables et des obstacles à l’adoption de ces innovations par les chercheurs. Les premiers adoptants des réseaux sociaux scientifiques, que ce soit dans un cadre éducatif, de réseautage lié à la recherche ou d’application des connaissances, sont sans doute les mieux placés pour mettre en évidence aussi bien les facteurs favorables que les facteurs défavorables présents dans leur environnement de travail. Méthodes : Les auteurs ont mené une étude selon la théorisatoin ancrée qui s’inscrit dans un courant constructiviste afin de cibler les éléments de l’expérience d’importants utilisateurs des réseaux sociaux scientifiques (p. ex. Twitter). Les participants ont été recrutés par échantillonnage en boule de neige et invités à des entretiens semi-structurés. Trois chercheurs ont analysé les transcriptions reçues selon la méthode de la comparaison constante. Par souci de rigueur, nous avons procédé à une vérification de l’analyse et à un contrôle des participants. Résultats : Dix-sept influenceurs émergents dans le domaine des réseaux sociaux scientifiques ont été recrutés. Après un codage axial, les 30 catalyseurs et les 21 obstacles à l’utilisation des réseaux sociaux scientifiques ont été mis en correspondance avec trois sphères d’influence : personnelle, institutionnelle et virtuelle. Les chercheurs proposent un cadre qui organise ces catalyseurs et ces obstacles autour d’un point de basculement où la durabilité devient possible. Conclusions : De multiples facilitateurs et obstacles ont été décrits pour influencer les utilisateurs de réseaux sociaux dans le domaine de la médecine universitaire. La classification de ces facteurs sur une échelle par type de cadre (personnel, institutionnel et virtuel) laisse entrevoir les structures sous-jacentes des écosystèmes universitaires qui sont propices au développement des réseaux sociaux et des innovations de ce type

Muscleblind-like 3 deficit results in a spectrum of age-associated pathologies observed in myotonic dystrophy.

Myotonic dystrophy type I (DM1) exhibits distinctive disease specific phenotypes and the accelerated onset of a spectrum of age-associated pathologies. In DM1, dominant effects of expanded CUG repeats result in part from the inactivation of the muscleblind-like (MBNL) proteins. To test the role of MBNL3, we deleted Mbnl3 exon 2 (Mbnl3(ΔE2)) in mice and examined the onset of age-associated diseases over 4 to 13 months of age. Accelerated onset of glucose intolerance with elevated insulin levels, cardiac systole deficits, left ventricle hypertrophy, a predictor of a later onset of heart failure and the development of subcapsular and cortical cataracts is observed in Mbnl3(ΔE2) mice. Retention of embryonic splice isoforms in adult organs, a prominent defect in DM1, is not observed in multiple RNAs including the Insulin Receptor (Insr), Cardiac Troponin T (Tnnt2), Lim Domain Binding 3 (Ldb3) RNAs in Mbnl3(ΔE2) mice. Although rare DM1-like splice errors underlying the observed phenotypes cannot be excluded, our data in conjunction with the reported absence of alternative splice errors in embryonic muscles of a similar Mbnl3(ΔE2) mouse by RNA-seq studies, suggest that mechanisms distinct from the adult retention of embryonic splice patterns may make important contributions to the onset of age-associated pathologies in DM1

In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice

Although tau is a cytoplasmic protein, it is also found in brain extracellular fluids, e.g., CSF. Recent findings suggest that aggregated tau can be transferred between cells and extracellular tau aggregates might mediate spread of tau pathology. Despite these data, details of whether tau is normally released into the brain interstitial fluid (ISF), its concentration in ISF in relation to CSF, and whether ISF tau is influenced by its aggregation are unknown. To address these issues, we developed a microdialysis technique to analyze monomeric ISF tau levels within the hippocampus of awake, freely moving mice. We detected tau in ISF of wild-type mice, suggesting that tau is released in the absence of neurodegeneration. ISF tau was significantly higher than CSF tau and their concentrations were not significantly correlated. Using P301S human tau transgenic mice (P301S tg mice), we found that ISF tau is fivefold higher than endogenous murine tau, consistent with its elevated levels of expression. However, following the onset of tau aggregation, monomeric ISF tau decreased markedly. Biochemical analysis demonstrated that soluble tau in brain homogenates decreased along with the deposition of insoluble tau. Tau fibrils injected into the hippocampus decreased ISF tau, suggesting that extracellular tau is in equilibrium with extracellular or intracellular tau aggregates. This technique should facilitate further studies of tau secretion, spread of tau pathology, the effects of different disease states on ISF tau, and the efficacy of experimental treatments

Spatial risk modeling of cattle depredation by black vultures in the midwestern United States

ock operations through depredation of stock are a cause of human‐wildlife conflict. Management of such conflict requires identifying environmental and non‐environmental factors specific to a wildlife species\u27 biology and ecology that influence the potential for livestock depredation to occur. Identification of such factors can improve understanding of the conditions placing livestock at risk. Black vultures (Coragyps atratus) have expanded their historical range northward into the midwestern United States. Concomitantly, an increase in concern among agricultural producers regarding potential black vulture attacks on livestock has occurred. We estimated area with greater or lesser potential for depredation of domestic cattle by black vultures across a 6‐state region in the midwestern United States using an ensemble of small models (ESM). Specifically, we identified landscape‐scale spatial factors, at a zip code resolution, associated with reported black vulture depredation on cattle in midwestern landscapes to predict future potential livestock depredation. We hypothesized that livestock depredation would be greatest in areas with intensive beef cattle production close to preferred black vulture habitat (e.g., areas with fewer old fields and early successional vegetation paired with more direct edge between older forest and agricultural lands). We predicted that the density of cattle within the county, habitat structure, and proximity to anthropogenic landscape features would be the strongest predictors of black vulture livestock‐depredation risk. Our ESM estimated the relative risk of black vulture‐cattle depredation to be between 0.154–0.631 across our entire study area. Consistent with our hypothesis, areas of greatest predicted risk of depredation correspond with locations that are favorable to vulture life‐history requirements and increased potential to encounter livestock. Our results allow wildlife managers the ability to predict where black vulture depredation of cattle is more likely to occur in the future. It is in these areas where extension and outreach efforts aimed at mitigating this conflict should be focused. Researchers and wildlife managers interested in developing or employing tools aimed at mitigating livestock‐vulture conflicts can also leverage our results to select areas where depredation is most likely to occur