An Electrophysiological Experimental Study on the Spontaneous Sympathetic Nerve Activity in the Rostral Ventrolateral Medulla Oblongata

The sympathetic postganglionic nerve fibers, which are controlled by preganglionic fibers originating from  specific nuclei in the medulla oblongata, and the thoracic and upper lumbar segments of the spinal cord,  together with the local autoregulatory mechanisms and circulating hormones, directly influence the cardiovascular  function. Recently, the studies on the sympathetic preganglionic fibers have remarkably progressed,  and the anatomical (Strack et al., 1988), functional (Janig, 1985), and chemical (Krukoff, 1985)  characteristics of the synaptic input have been clarified. However, the peripheral sympathetic nerve activities  vary depending on the organs concerned (including the skin, muscle, or internal organs) as they have  their own physiological characteristics (Janig and McLachlan, 1986) including the response pattern to the  peripheral receptor stimulation. Many areas, including the histological and functional roles of the peripheral  part, nerve centers, and central pathway of the circulatory system, are still unknown. The peripheral sympathetic nerve activities in humans consist of the skin sympathetic activity (SSA) that  controls the sweat glands / skin vasomotion, and the muscle sympathetic activity (MSA) that controls the  vascular smooth muscles in the skeletal muscles, and each activity has different characteristics. SSA  involving regulation of the body temperature and MSA involving regulation of the blood pressure can be  separately recorded (Burke et al., 1977; Hagbarth et al., 1975; Vallbo et al., 1979; Wallin and Eckberg,  1982; Yatomi et al., 1989) from the sympathetic postganglionic efferent fibers by microneurography  (Hagbarth et al., 1972). By recording and comparing the action patterns and responses to stimulations of the premotor nuclei, along  with other vital rhythms, we hoped to clarify the complex mechanism of the sympathetic nerve activities  and to contribute in the treatment of disorders resulting from sympathetic dysfunction. We also report our  findings on the premotor nuclei that produce sympathetic preganglionic fiber activities by using topographic  mapping analysis of the changes in the central action potentials in the rostral ventrolateral medulla  oblongata (RVLM) region to visually capture the complicated action patterns to compare the cross correlations  with MSA and SSA using microneurography and ECG.

Current Performance and On-Going Improvements of the 8.2 m Subaru Telescope

An overview of the current status of the 8.2 m Subaru Telescope constructed and operated at Mauna Kea, Hawaii, by the National Astronomical Observatory of Japan is presented. The basic design concept and the verified performance of the telescope system are described. Also given are the status of the instrument package offered to the astronomical community, the status of operation, and some of the future plans. The status of the telescope reported in a number of SPIE papers as of the summer of 2002 are incorporated with some updates included as of 2004 February. However, readers are encouraged to check the most updated status of the telescope through the home page, http://subarutelescope.org/index.html, and/or the direct contact with the observatory staff.Comment: 18 pages (17 pages in published version), 29 figures (GIF format), This is the version before the galley proo

Ablation of TSC2 Enhances Insulin Secretion by Increasing the Number of Mitochondria through Activation of mTORC1

) mice. The present study examines the effects of TSC2 ablation on insulin secretion from pancreatic beta cells. mice and TSC2 knockdown insulin 1 (INS-1) insulinoma cells treated with small interfering ribonucleic acid were used to investigate insulin secretion, ATP content and the expression of mitochondrial genes. mice exhibit hyperinsulinemia due to an increase in the number of mitochondria as well as enlargement of individual beta cells via activation of mTORC1.Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target