54 research outputs found

    A fluorescent microporous crystalline dendrimer discriminates vapour molecules

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    A self-assembled crystalline microporous dendrimer framework (MDF) exhibits novel turn-on and ratiometric fluorescence upon exposure to solvent vapours. The donor–acceptor character, combined with the large surface area (>650 m2 g−1), allows the MDF to discriminate vapours of volatile solvents with turn-on and colour change of photoluminescence

    The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

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    「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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

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    「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

    Nutritional signaling via free fatty acid receptors

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    Excess energy is stored primarily as triglycerides, which are mobilized when demand for energy arises. Dysfunction of energy balance by excess food intake leads to metabolic diseases, such as obesity and diabetes. Free fatty acids (FFAs) provided by dietary fat are not only important nutrients, but also contribute key physiological functions via FFA receptor (FFAR)-mediated signaling molecules, which depend on FFAs’ carbon chain length and the ligand specificity of the receptors. Functional analyses have revealed that FFARs are critical for metabolic functions, such as peptide hormone secretion and inflammation, and contribute to energy homeostasis. In particular, recent studies have shown that the administration of selective agonists of G protein-coupled receptor (GPR) 40 and GPR120 improved glucose metabolism and systemic metabolic disorders. Furthermore, the anti-inflammation and energy metabolism effects of short chain FAs have been linked to the activation of GPR41 and GPR43. In this review, we summarize recent progress in research on FFAs and their physiological roles in the regulation of energy metabolism

    Physiological and Immunological Differences in Cattle under Grazing or Confinement Condition

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    Potential impact of botanically diverse pasture on the nutritional, physiological, and immunological status of grazing cows

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    The aim of this study was to reveal the potential impact of botanically diverse pasture on the nutritional, physiological, and immunological status of grazing cattle using multifaceted indices. Ten Japanese black beef cows (325.5 ± 40.6 kg of BW, 7.9 ± 3.8 years of age) were used in this experiment. Five of them grazed on a 1.8 ha grassland (botanically diverse pasture: DP) that was composed of sown grassland and grazable forestland (approximately 34 plant species). The other five cows grazed on 1.0 ha of sown grassland with only a few plant species (botanically monotonous pasture: MP, approximately 5 plant species) for two months. Blood samples were collected approximately every two weeks. In DP cows, the hemoglobin (HGB) concentration, hematocrit (HCT) ratio, and superoxide dismutase (SOD) activity increased linearly after the start of grazing, as did plasma sodium (Na), calcium (Ca), and potassium (K) concentrations. Urea nitrogen (UN) levels were higher in DP than in MP cows throughout the grazing period, whereas in MP cows, the red blood cell (RBC) count, HGB concentration, and HCT ratio decreased quadratically after the start of grazing. The DP cows gained more BW than the MP cows throughout the grazing period. Thus, the increased intake and/or the change in the ingested plant species in DP cows might have promoted the increase in the plasma UN concentration. In summary, the present study showed that grazing in botanically diverse pasture improved the nutritional and physiological status of cows; however, it aggravated the imbalance of protein and energy intake induced by grazing within two months

    Sustainable goat grazing for managing abandoned fields : Dynamics of vegetation quality, quantity and nutritional status of goats over five years

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    Grazing goats have potential for use in managing abandoned fields. However, it is unclear how long-term grazing affects goats as a result of vegetational changes in abandoned fields. This study aimed to assess the dynamics of vegetation quality and quantity and the nutritional status of goats for five years in an abandoned field at different stocking rates: high stocking rate (HS: 30–33 goats/ha) and low stocking rate (LS: 14 goats/ha). In five years, the dominant plant species changed from bamboo (Phyllostachys edulis) to tufted grass species at the HS, whereas dwarf bamboo (Pleioblastus argenteostriatus) dominated throughout the five years at the LS. The annual plant biomass at both stocking rates was similar and varied from year to year. Crude protein content in the goats\u27 diet did not show any seasonal or annual trend regardless of the stocking rate. Neutral detergent fiber content in the HS diet did not show any seasonal or annual trend; however, that in the LS diet linearly increased with the grazing year. The dry matter (DM) intake for goats at the LS decreased linearly with the grazing year (p < 0.05), whereas that for goats at the HS did not show any trend. The DM digestibility was higher for goats at the HS than for goats at the LS (p < 0.05). Serum parameters did not show a negative nutritional status of the goats over the study years. Annual daily gain was positive throughout the grazing years regardless of the stocking rate. Consequently, within the stocking rate range studied here, long-term goat grazing changes the quality of vegetation in an abandoned field; however, goats can maintain their nutritional status and body weight for five years. Thus, goat grazing is a feasible way to control abandoned vegetation over the long term
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