Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection. However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response.National Institutes of Health (U.S.

ICAR: endoscopic skull‐base surgery

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Clinical outcome of patients with malignant ventricular tachyarrhythmias and a multiprogrammable implantable cardioverter-defibrillator implanted with or without thoracotomy: an international multicenter study

Objectives. The long term efficacy and safety of a third-generation implantable cardioverter-defibrillator implanted with thoracotomy and nonthoracotomy lead systems was evaluated in a multicenter international study. Background. The clinical impact of transvenous leads for nonthoracotomy implantation and pacing for bradyarrhythmias and tachyarrhythmias in implantable cardioverter defibrillator systems is not well defined. Methods. The safety of the implantation procedure and clinical outcome of 1,221 patients with symptomatic and life-threatening ventricular tachyarrhythmias who underwent implantation of a third generation cardioverter defibrillator using either a thoracotomy approach with epicardial leads (616 patients) or a nonthoracotomy approach with endocardial leads (605 patients) in a nonrandomized manner was analyzed. The implantable cardioverter defibrillator system permitted pacing, cardioversion, defibrillation, arrhythmia event memory and noninvasive tachycardia induction. Results. Successful implantation of an endocardial lead system was achieved in 605 (88.2%) of 686 patients and an epicardial system in 614 (99.7%) of 616 (p 0.2). Conclusions. Third-generation cardioverter defibrillators with monophasic waveforms can be successfully implanted with epicardial (99.7%) and endocardial (88.2%) lead systems. We conclude that endocardial leads should be the implant technique of first choice. Improved patient management and tolerance for device therapy is achieved with the addition of antitachycardia pacemaker capability in these systems

Life-History Responses to the Altitudinal Gradient

We review life-history variation along elevation in animals and plants and illustrate its drivers, mechanisms and constraints. Elevation shapes life histories into suites of correlated traits that are often remarkably convergent among organisms facing the same environmental challenges. Much of the variation observed along elevation is the result of direct physiological sensitivity to temperature and nutrient supply. As a general rule, alpine populations adopt ‘slow’ life cycles, involving long lifespan, delayed maturity, slow reproductive rates and strong inversions in parental care to enhance the chance of recruitment. Exceptions in both animals and plants are often rooted in evolutionary legacies (e.g. constraints to prolonging cycles in obligatory univoltine taxa) or biogeographic history (e.g. location near trailing or leading edges). Predicting evolutionary trajectories into the future must take into account genetic variability, gene flow and selection strength, which define the potential for local adaptation, as well as the rate of anthropogenic environmental change and species’ idiosyncratic reaction norms. Shifts up and down elevation in the past helped maintain genetic differentiation in alpine populations, with slow life cycles contributing to the accumulation of genetic diversity during upward migrations. Gene flow is facilitated by the proximity of neighbouring populations, and global warming is likely to move fast genotypes upwards and reduce some of those constraints dominating alpine life. Demographic buffering or compensation may protect local alpine populations against trends in environmental conditions, but such mechanisms may not last indefinitely if evolutionary trajectories cannot keep pace with rapid changes.Peer reviewe