PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy

Defective mitochondrial quality control is shown to be a mechanism for neurodegeneration in some forms of Parkinson's disease

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

「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

「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

The dynamics of carbon stored in xylem sapwood to drought-induced hydraulic stress in mature trees.

Climate-induced forest die-off is widespread in multiple biomes, strongly affecting the species composition, function and primary production in forest ecosystems. Hydraulic failure and carbon starvation in xylem sapwood are major hypotheses to explain drought-induced tree mortality. Because it is difficult to obtain enough field observations on drought-induced mortality in adult trees, the current understanding of the physiological mechanisms for tree die-offs is still controversial. However, the simultaneous examination of water and carbon uses throughout dehydration and rehydration processes in adult trees will contribute to clarify the roles of hydraulic failure and carbon starvation in tree wilting. Here we show the processes of the percent loss of hydraulic conductivity (PLC) and the content of nonstructural carbohydrates (NSCs) of distal branches in woody plants with contrasting water use strategy. Starch was converted to soluble sugar during PLC progression under drought, and the hydraulic conductivity recovered following water supply. The conversion of NSCs is strongly associated with PLC variations during dehydration and rehydration processes, indicating that stored carbon contributes to tree survival under drought; further carbon starvation can advance hydraulic failure. We predict that even slow-progressing drought degrades forest ecosystems via carbon starvation, causing more frequent catastrophic forest die-offs than the present projection

Formulations of Job Strain and Psychological Distress: A Four-year Longitudinal Study in Japan

Background: Different job strain formulations based on the Job Demand-Control model have been developed. This study evaluated longitudinal associations between job strain and psychological distress and whether associations were influenced by six formulations of job strain, including quadrant (original and simplified), subtraction, quotient, logarithm quotient, and quartile based on quotient, in randomly selected Japanese workers. Methods: Data were from waves I and II of the Survey of Midlife in Japan (MIDJA), with a 4-year follow-up period. The study sample consisted of 412 participants working at baseline and had complete data on variables of interest. Associations between job strain at baseline and psychological distress at follow-up were assessed via multivariable linear regression, and results were expressed as β coefficients and 95% confidence intervals including R2 and Akaike information criterion (AIC) evaluation. Results: Crude models revealed that job strain formulations explained 6.93–10.30% of variance. The AIC ranged from 1475.87 to 1489.12. After accounting for sociodemographic and behavioral factors and psychological distress at baseline, fully-adjusted models indicated significant associations between all job strain formulations at baseline and psychological distress at follow-up: original quadrant (β: 1.16, 95% CI: 0.12, 2.21), simplified quadrant (β: 1.01, 95% CI: 0.18, 1.85), subtraction (β: 0.39, 95% CI: 0.09, 0.70), quotient (β: 0.37, 95% CI: 0.08, 0.67), logarithm quotient (β: 0.42, 95% CI: 0.12, 0.72), and quartile based on quotient (β: 1.22, 95% CI: 0.36, 2.08). Conclusion: Six job strain formulations showed robust predictive power regarding psychological distress over 4 years among Japanese workers

Bootstrap Method of Eco-Efficiency in the Brazilian Agricultural Industry

With the economic growth of the Brazilian agroindustry, it is necessary to evaluate the efficiency of this activity in relation to environmental demands for the country’s economic, social, and sustainable development. Within this perspective, the present research aims to examine the eco-efficiency of agricultural production in Brazilian regions, covering 5563 municipalities in the north, northeast, center-west, southeast, and south regions, using data from 2016–2017. In this sense, this study uses the DEA methods (classical and stochastic) and the computational bootstrap method to remove outliers and measure eco-efficiency. The findings lead to two fundamental conclusions: first, by emulating the benchmarks, it is feasible to increase annual revenue and preserved areas to an aggregated regional level by 20.84% while maintaining the same inputs. Given that no municipality has reached an eco-efficiency value equal to 1, there is room for optimization and improvement of production and greater sustainable development of the municipalities. Secondly, climatic factors notably influence eco-efficiency scores, suggesting that increasing temperatures and decreasing precipitation can positively impact eco-efficiency in the region. These conclusions, dependent on regional characteristics, offer valuable information for policymakers to design strategies that balance economic growth and environmental preservation. Furthermore, adaptive policies and measures can be implemented to increase the resilience of local producers and reduce vulnerability to changing climate conditions