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Medical students need to understand core neuroscience principles as a foundation for their required clinical experiences in neurology. In fact, they need a solid neuroscience foundation for their clinical experiences in all other medical disciplines also, because the nervous system plays such a critical role in the function of every organ system. Due to the rapid pace of neuroscience discoveries, it is unrealistic to expect students to master the entire field. It is also unnecessary, as students can expect to have ready access to electronic reference sources no matter where they practice. In the pre-clerkship phase of medical school, the focus should be on providing students with the foundational knowledge to use those resources effectively and interpret them correctly. This article describes an organizational framework for teaching the essential neuroscience background needed by all physicians. This is particularly germane at a time when many medical schools are re-assessing traditional practices and instituting curricular changes such as competency-based approaches, earlier clinical immersion, and increased emphasis on active learning. This article reviews factors that should be considered when developing the pre-clerkship neuroscience curriculum, including goals and objectives for the curriculum, the general topics to include, teaching and assessment methodology, who should direct the course, and the areas of expertise of faculty who might be enlisted as teachers or content experts. These guidelines were developed by a work group of experienced educators appointed by the Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN). They were then successively reviewed, edited, and approved by the entire UES, the AAN Education Committee, and the AAN Board of Directors.

The flexible control of sequential behavior is a fundamental aspect of speech, enabling endless reordering of a limited set of learned vocal elements (syllables or words). Songbirds are phylogenetically distant from humans but share both the capacity for vocal learning and neural circuitry for vocal control that includes direct pallial-brainstem projections. Based on these similarities, we hypothesized that songbirds might likewise be able to learn flexible, moment-by-moment control over vocalizations. Here, we demonstrate that Bengalese finches (Lonchura striata domestica), which sing variable syllable sequences, can learn to rapidly modify the probability of specific sequences (e.g. ‘ab-c’ versus ‘ab-d’) in response to arbitrary visual cues. Moreover, once learned, this modulation of sequencing occurs immediately following changes in contextual cues and persists without external reinforcement. Our findings reveal a capacity in songbirds for learned contextual control over syllable sequencing that parallels human cognitive control over syllable sequencing in speech.

RPE65 is the essential trans-cis isomerase of the classical retinoid (visual) cycle. Mutations in RPE65 give rise to severe retinal dystrophies, most of which are associated with loss of protein function and recessive inheritance. The only known exception is a c.1430G>A (D477G) mutation that gives rise to dominant retinitis pigmentosa with delayed onset and choroidal and macular involvement. Position 477 is distant from functionally critical regions of RPE65. Hence, the mechanism of D477G pathogenicity remains unclear, although protein misfolding and aggregation mechanisms have been suggested. We characterized a D477G knock-in mouse model which exhibited mild age-dependent changes in retinal structure and function. Immunoblot analysis of protein extracts from the eyes of these knock-in mice demonstrated the presence of ubiquitinated RPE65 and reduced RPE65 expression. We observed an accumulation of retinyl esters in the knock-in mice as well as a delay in rhodopsin regeneration kinetics and diminished electroretinography responses, indicative of RPE65 functional impairment induced by the D477G mutation in vivo. However, a cell line expressing D477G RPE65 revealed protein expression levels, cellular localization and retinoid isomerase activity comparable to cells expressing wild-type protein. Structural analysis of an RPE65 chimera suggested that the D477G mutation does not perturb protein folding or tertiary structure. Instead, the mutation generates an aggregation-prone surface that could induce cellular toxicity through abnormal complex formation as suggested by crystal packing analysis. These results indicate that a toxic gain-of-function induced by the D477G RPE65 substitution may play a role in the pathogenesis of this form of dominant retinitis pigmentosa.

The article focuses on critiquing bioethics' alignment with neoliberal economic principles, particularly in contexts like vaccine-sensitive rationing which it argues often neglects systemic injustices and economic complexities. Topics include the critique of principlist approaches in bioethics, the influence of market ideologies on ethical frameworks, and the marginalization of voices critical of neoliberalism within bioethical discourse.

Background: Extracellular vesicles (EVs) are released by red blood cells (RBCs) throughout their life‐span and also during hypothermic storage when they accumulate in the blood bag. We queried whether stored RBCs with increased cation permeability, either from donors with familial pseudohyperkalaemia (FP) or caused by irradiation, vesiculate more readily. Study Design and Methods: Recent technical advances have revealed at least two sub‐populations of MVs in RBC storage units: macrovesicles (2–6 μm) and microvesicles (1–2 μm). Using nanoparticle tracking analysis, imaging flow cytometry, and protein quantification methods, we measured and characterized vesicles released by RBCs from control and FP individuals at three different storage time‐points (day 4, day 17, and day 29). The RBCs had either been stored untreated or irradiated on either day 1 or day 14 of storage. Results: We found no difference in the number or size of vesicles released between cation‐leaky FP RBCs and non‐FP controls. Similarly, irradiated and non‐irradiated RBCs showed very similar patterns of vesicle release to during cold‐storage. The only significant difference in vesicle release was the increase in accumulated vesicles with length of storage time which has been reported previously. Discussion: EVs in stored blood are potential contributors to adverse transfusion reactions. The number of vesicles released during 35‐day hypothermic storage varies between donors and increases with storage duration. However, increased cation permeability and irradiation do not appear to affect vesicle formation during RBC cold‐storage. [ABSTRACT FROM AUTHOR]

Chemical changes in leaf input to forest soils have been reported to affect decay processes. In this work, litter mass loss and decomposition constants (k) during 200 days in solid-state fermentation of the native tree Celtis tala Gill. ex Planch. and the exotic one Ligustrum lucidum Ait. with three common litter saprotrophic basidiomycetes were compared. Alterations in litter quality were characterized by solid-state [sup.13]C NMR spectroscopy, pH, soluble sugars, ammonium, proteins, and phenol content determination and were associated with extracellular lignocellulolytic enzyme production. Differences in substrate decomposition related to litter type were observed for Leratiomyces ceres, achieving a higher k in the exotic L. lucidum litter, which might be attributed to the induction of manganese peroxidase activity. Substrate preference for alkyl C and more degradation of lignified compounds were found in such substrates. Although no statistical differences in mass loss were observed for the rest of the fungi assayed, we detected changes in several of the parameters evaluated. This suggests that exotic invasions may alter ecosystem functioning by accelerating decomposition processes through an increased fungal ligninolytic activity. Key words: basidiomycetes, extracellular enzymes, solid-state fermentation, litter quality, carbon-13 cross- polarization magicangle spinning nuclear magnetic resonance. On rapporte que des changements d'ordre chimique dans l'apport des feuilles aux sols forestiers ont un impact sur les processus de decomposition. La perte de masse de la litiere et la constante de decomposition (k) ont ete comparees durant 200 jours de fermentation en milieu solide de l'espece indigene Celtis tala Gill. ex Planch. et de l'espece exotique Ligustrum lucidum Ait. avec trois basidiomycetes saprophytes communs dans la litiere. Les alterations de la qualite de la litiere ont ete caracterisees par la spectroscopie RMN du [sup.13]C en phase solide, ainsi que la mesure du pH, des sucres solubles, de l'ammonium, des proteines et de la teneur en phenol. De plus, les alterations ont ete associees a la production d'enzymes lignocellulosiques extracellulaires. Des differences dans la decomposition du substrat en lien avec le type de litiere ont ete observees avec Leratiomyces ceres qui produisait une valeur de k plus elevee dans la litiere de l'espece exotique L. lucidum, laquelle pourrait etre due a l'induction de l'activite de la manganese peroxydase. La preference du substrat pour le carbone alkyle et une meilleure degradation des composes lignifies ont ete observees dans de tels substrats. Meme si aucunes differences statistiquement significatives dans la perte de masse n'ont ete observees avec les autres champignons testes, nous avons detecte des changements chez plusieurs des parametres qui ont ete evalues. Cela indique que les invasions exotiques peuvent alterer le fonctionnement de l'ecosysteme en accelerant les processus de decomposition par le biais d'une augmentation de l'activite ligninolytique des champignons. [Traduit par la Redaction] Mots-cles: basidiomycetes, enzymes extracellulaires, fermentation en milieu solide, qualite de la litiere, resonance magnetique nucleaire par rotation a l'angle magique et polarisation croisee du carbone 13., Introduction Invasion of exotic plants in pristine terrestrial ecosystems is a major environmental problem due to alterations in the vegetal community with the consequent detrimental impact on the activity of [...]

The gut‐brain axis is increasingly recognized as an important pathway involved in cocaine use disorder. Microbial products of the murine gut have been shown to affect striatal gene expression, and depletion of the microbiome by antibiotic treatment alters cocaine‐induced behavioral sensitization in C57BL/6J male mice. Some reports suggest that cocaine‐induced behavioral sensitization is correlated with drug self‐administration behavior in mice. Here, we profile the composition of the naïve microbiome and its response to cocaine sensitization in two collaborative cross (CC) strains. These strains display extremely divergent behavioral responses to cocaine sensitization. A high‐responding strain, CC004/TauUncJ (CC04), has a gut microbiome that contains a greater amount of Lactobacillus than the cocaine‐nonresponsive strain CC041/TauUncJ (CC41). The gut microbiome of CC41 is characterized by an abundance of Eisenbergella, Robinsonella and Ruminococcus. In response to cocaine, CC04 has an increased Barnsiella population, while the gut microbiome of CC41 displays no significant changes. PICRUSt functional analysis of the functional potential of the gut microbiome in CC04 shows a significant number of potential gut‐brain modules altered after exposure to cocaine, specifically those encoding for tryptophan synthesis, glutamine metabolism, and menaquinone synthesis (vitamin K2). Depletion of the microbiome by antibiotic treatment revealed an altered cocaine‐sensitization response following antibiotics in female CC04 mice. Depleting the microbiome by antibiotic treatment in males revealed increased infusions for CC04 during a cocaine intravenous self‐administration dose–response curve. Together these data suggest that genetic differences in cocaine‐related behaviors may involve the microbiome. [ABSTRACT FROM AUTHOR]