70 research outputs found

    Comparative cellular analysis of motor cortex in human, marmoset and mouse

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    The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals(1). 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.Cardiovascular Aspects of Radiolog

    Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

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    To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

    The effect of gain crystal temperature on a miniature single frequency Nd:YVO4 laser

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    Summary form only given. Microchip lasers represent highly efficient sources of laser radiation and are easily mass produced at low cost. However, it is difficult to operate them on a single frequency at output powers greater than about 150 mW. Hence, laser geometries that maintain the simplicity exhibited by microchip lasers yet which can be operated on a single frequency at higher output powers are of great interest. In the paper we demonstrate the potential of a birefringent filter, consisting of a Brewster plate and a birefringent crystal, as a frequency selective element in a micro-laser which has additionally, a birefringent gain crystal. Single frequency output powers greater than 760 mW have been obtained at 1064 nm for 2 W of diode laser pump powe

    Compact and efficient single frequency Nd:YVO4 laser with variable longitudinal mode discrimination

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    We show for the first time that the longitudinal-mode discrimination in a birefringently filtered laser can be tuned through the variation of the waveplating action of the gain crystal. In this way, the laser can be optimized for either high intermodal discrimination or for frequency tuning with reduced output power rolloff. Up to 760 mW of single-frequency 1064-nm output is obtained from a compact diode-pumped source that can be frequency chirped over 6.5 GHz

    Acid esterase in human arteries

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