A voucher is a permanently preserved specimen that is maintained in an accessible collection. In genomics, vouchers serve as the physical evidence for the taxonomic identification of genome assemblies. Unfortunately, the vast majority of vertebrate genomes stored in the GenBank database do not refer to voucher specimens. Here, we urge researchers generating new genome assemblies to deposit voucher specimens in accessible, permanent research collections, and to link these vouchers to publications, public databases, and repositories. We also encourage scientists to deposit voucher specimens in order to recognize the work of local field biologists and promote a diverse and inclusive knowledge base, and we recommend best practices for voucher deposition to prevent taxonomic errors and ensure reproducibility and legality in genetic studies.Neurotransmitter release is a highly controlled process by which synapses can critically regulate information transfer within neural circuits. While presynaptic receptors - typically activated by neurotransmitters and modulated by neuromodulators - provide a powerful way of fine-tuning synaptic function, their contribution to activity-dependent changes in transmitter release remains poorly understood. Here, we report that presynaptic NMDA receptors (preNMDARs) at mossy fiber boutons in the rodent hippocampus can be activated by physiologically relevant patterns of activity and selectively enhance short-term synaptic plasticity at mossy fiber inputs onto CA3 pyramidal cells and mossy cells, but not onto inhibitory interneurons. Moreover, preNMDARs facilitate brain-derived neurotrophic factor release and contribute to presynaptic calcium rise. selleck Taken together, our results indicate that by increasing presynaptic calcium, preNMDARs fine-tune mossy fiber neurotransmission and can control information transfer during dentate granule cell burst activity that normally occur in vivo.Skeletal muscle excitation-contraction (EC) coupling roots in Ca2+-influx-independent inter-channel signaling between the sarcolemmal dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR1) in the sarcoplasmic reticulum. Although DHPR Ca2+ influx is irrelevant for EC coupling, its putative role in other muscle-physiological and developmental pathways was recently examined using two distinct genetically engineered mouse models carrying Ca2+ non-conducting DHPRs DHPR(N617D) (Dayal et al., 2017) and DHPR(E1014K) (Lee et al., 2015). Surprisingly, despite complete block of DHPR Ca2+-conductance, histological, biochemical, and physiological results obtained from these two models were contradictory. Here, we characterize the permeability and selectivity properties and henceforth the mechanism of Ca2+ non-conductance of DHPR(N617). Our results reveal that only mutant DHPR(N617D) with atypical high-affinity Ca2+ pore-binding is tight for physiologically relevant monovalent cations like Na+ and K+. Consequently, we propose a molecular model of cooperativity between two ion selectivity rings formed by negatively charged residues in the DHPR pore region. Considering the remaining threat of drug-resistantmutations (DRMs) to antiretroviral treatment (ART) efficacy, we investigated how the selective pressure of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes drives certain DRMs' emergence and retention. We systematically screened DRMHLA class I allele combinations in 3997 ART-naïve Swiss HIV Cohort Study (SHCS) patients. For each pair, a logistic regression model preliminarily tested for an association with the DRM as the outcome. The three HLADRM pairs remaining after multiple testing adjustment were analyzed in three ways cross-sectional logistic regression models to determine any HLA/infection time interaction, survival analyses to examine if HLA type correlated with developing specific DRMs, and via NetMHCpan to find epitope binding evidence of immune escape. Only one pair, RT-E138HLA-B18, exhibited a significant interaction between infection duration and HLA. The survival analyses predicted two pairs with an increased hazard of developing DRMs RT-E138HLA-B18 and RT-V179HLA-B35. RT-E138HLA-B18 exhibited the greatest significance in both analyses (interaction term odds ratio [OR] 1.169 [95% confidence interval (CI) 1.075-1.273]; p-value<0.001; survival hazard ratio 12.211 [95% CI 3.523-42.318]; p-value<0.001). The same two pairs were also predicted by netMHCpan to have epitopic binding. We identified DRMHLA pairs where HLA presence is associated with the presence or emergence of the DRM, indicating that the selective pressure for these mutations alternates direction depending on the presence of these HLA alleles. Funded by the Swiss National Science Foundation within the framework of the SHCS, and the University of Zurich, University Research Priority Program Evolution in Action From Genomes Ecosystems, in Switzerland.Funded by the Swiss National Science Foundation within the framework of the SHCS, and the University of Zurich, University Research Priority Program Evolution in Action From Genomes Ecosystems, in Switzerland.γ-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the human brain and can be measured with magnetic resonance spectroscopy (MRS). Conflicting accounts report decreases and increases in cortical GABA levels across the lifespan. This incompatibility may be an artifact of the size and age range of the samples utilized in these studies. No single study to date has included the entire lifespan. In this study, eight suitable datasets were integrated to generate a model of the trajectory of frontal GABA estimates (as reported through edited MRS; both expressed as ratios and in institutional units) across the lifespan. Data were fit using both a log-normal curve and a nonparametric spline as regression models using a multi-level Bayesian model utilizing the Stan language. Integrated data show that an asymmetric lifespan trajectory of frontal GABA measures involves an early period of increase, followed by a period of stability during early adulthood, with a gradual decrease during adulthood and aging that is described well by both spline and log-normal models.