The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

Over the course of a mission to the International Space Station (ISS) crew members are exposed to a number of stressors that can potentially alter the composition of their microbiomes and may have a negative impact on astronauts’ health. Here we investigated the impact of long-term space exploration on the microbiome of nine astronauts that spent six to twelve months in the ISS. We present evidence showing that the microbial communities of the gastrointestinal tract, skin, nose and tongue change during the space mission. The composition of the intestinal microbiota became more similar across astronauts in space, mostly due to a drop in the abundance of a few bacterial taxa, some of which were also correlated with changes in the cytokine profile of crewmembers. Alterations in the skin microbiome that might contribute to the high frequency of skin rashes/hypersensitivity episodes experienced by astronauts in space were also observed. The results from this study demonstrate that the composition of the astronauts’ microbiome is altered during space travel. The impact of those changes on crew health warrants further investigation before humans embark on long-duration voyages into outer space.

23The primary motor cortex (M1) is essential for voluntary fine motor control and is functionally conserved 24 across mammals. Using high-throughput transcriptomic and epigenomic profiling of over 450,000 single 25 nuclei in human, marmoset monkey, and mouse, we demonstrate a broadly conserved cellular makeup 26 of this region, whose similarity mirrors evolutionary distance and is consistent between the 27 transcriptome and epigenome. The core conserved molecular identity of neuronal and non-neuronal 28 types allowed the generation of a cross-species consensus cell type classification and inference of 29 conserved cell type properties across species. Despite overall conservation, many species 30 specializations were apparent, including differences in cell type proportions, gene expression, DNA 31 methylation, and chromatin state. Few cell type marker genes were conserved across species, 32 providing a short list of candidate genes and regulatory mechanisms responsible for conserved features 33 of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic 34 classification allowed the Patch-seq identification of layer 5 (L5) corticospinal Betz cells in non-human 35 primate and human and characterization of their highly specialized physiology and anatomy. These 36 findings highlight the robust molecular underpinnings of cell type diversity in M1 across mammals and 37 point to the genes and regulatory pathways responsible for the functional identity of cell types and their 38 species-specific adaptations. 39 40 distinguished on the basis of regions of open chromatin or DNA methylation 5,9,10 . Furthermore, several 48 recent studies have shown that transcriptomically-defined cell types can be aligned across species 2,11-49 13 , indicating that these methods provide a path to quantitatively study evolutionary conservation and 50 divergence at the level of cell types. However, application of these methods has been highly 51 fragmented to date. Human and mouse comparisons have been performed in different cortical regions, 52 using single-cell (with biases in cell proportions) versus single-nucleus (with biases in transcript 53 makeup) analysis, and most single-cell transcriptomic and epigenomic studies have been performed 54 independently. 55 56The primary motor cortex (MOp in mouse, M1 in human and non-human primates, all referred to as M1 57 herein) provides an ideal cortical region to address questions about cellular evolution in rodents and 58 primates by integrating these approaches. Unlike the primary visual cortex (V1), which is highly 59 specialized in primates, or frontal and temporal association areas, whose homologues in rodents 60 remain poorly defined, M1 is essential for fine motor control and is functionally conserved across 61 placental mammals. M1 is an agranular cortex, lacking a defined L4, although neurons with L4-like 62properties have been described 14 . L5 of carnivore and primate M1 contains exceptionally large 63 "giganto-cellular" corticospinal neurons (Betz c...

Exparel does not provide an opioid-sparing benefit or any secondary outcome benefit compared with placebo. Exparel may be associated with a marginal decrease in postoperative pain levels. (Parasternal Nerve Bock in Cardiac Patients; NCT01826851.).

Humans are host to a multitude of microorganisms that rapidly populate the body at birth, subject to a complex interplay that is dependent on host genetics, lifestyle, and environment. The host-associated microbiome, including the oral microbiome, presents itself in a complex ecosystem important to health and disease. As the most common chronic disease globally, dental caries is induced by hostmicrobial dysbiosis in children and adults. Multiple biological and environmental factors are likely to impact disease predisposition, onset, progression, and severity, yet longitudinal studies able to capture these influences are missing. To investigate how host genetics and environment influenced the oral microbial communities over time, we profiled supragingival plaque microbiomes of dizygotic and monozygotic twins during 3 visits over 12-months. Dental plaque DNA samples were amplified by targeting the 16S rRNA gene V4 region, and microbial findings were correlated with clinical, diet and genetic metadata. We observed that the oral microbiome variances were shaped primarily by the environment when compared to host genetics. Among the environmental factors shaping microbial changes of our subjects, significant metadata included age of the subject, and the age by which subjects initiated brushing habits, and the types of actions post-brushing. Relevant heritability of the microbiome included Actinomyces and Capnocytophaga in monozygotic twins and Kingella in dizygotic twins. Corynebacterium and Veillonella abundances were associated with age, whereas Aggregatibacter was associated with younger subjects. Streptococcus abundance showed an inverse association over time, and Selenomonas abundances increased with brushing frequency per day. Unraveling the exact biological mechanisms in caries has the potential to reveal novel host-microbial biomarkers, pathways, and targets important to effective preventive measures, and early disease control in children. Across various human body habitats, including the oral cavity, mutually beneficial relationships between the host and its microbiome lead to homeostatic phenotypic patterns. While shifts in gastrointestinal 1,2 and skin 3-5 habitats have advanced our understanding of host-microbial dysbiosis, the oral counterpart has not received the same level of mechanistic interrogation, particularly with respect to host genetics link. One central question remaining unanswered is the extent to which differences in the microbiome are explained by host genetics. As one of the most diverse microbial ecologies in humans, the oral microbiome has critical importance to local oral and systemic health. In fact, oral microbial dysbiosis underlies many human oral diseases with systemic consequences, but the exact mechanism regulating microbial patterns associated with health to disease transition and from acute to chronic lesions remains elusive. Loss of host-microbial homeostasis in the oral habitat leads to dysbiosis and a range of oral and systemic conditions, including caries, periodontal diseas...