Changes in ice thickness and flow velocity of Yala Glacier, Langtang Himal, Nepal, from 1982 to 2009

ABSTRACT. To investigate recent glacier changes in the Himalayan region, we carried out GPS and ground-penetrating radar (GPR) measurements at Yala Glacier, a benchmark glacier in Nepal. Glacier surface elevation and ice thickness were surveyed along a 1. . Our results indicate that Yala Glacier has lost $40% of its ice volume over the last 27 years and that the rate of the mass loss has accelerated over the last decade

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

Changes in ice thickness and flow velocity of Yala Glacier, Langtang Himal, Nepal, from 1982 to 2009

To investigate recent glacier changes in the Himalayan region, we carried out GPS and ground-penetrating radar (GPR) measurements at Yala Glacier, a benchmark glacier in Nepal. Glacier surface elevation and ice thickness were surveyed along a 1.5 km profile from the glacier top to the terminus. Ice flow velocity was measured at five locations by surveying stakes for either 1 year or 4 day periods. Obtained surface elevation and ice velocity were compared with those measured in 1982 and 1996. The mean ice thickness along the radar profile was 36 m in 2009 and the ice has been thinning at rates of -0.69 +/- 0.25 and -0.75 +/- 0.24 m a(-1) during the periods 1982-96 and 1996-2009, respectively. The thinning rate increases down-glacier, reaching a magnitude up to -1.8 m a(-1) near the terminus from 1996 to 2009. The ice velocity has reduced by >70% from 1982 to 2009 in the lower half of the glacier. By assuming a constant driving stress over the glacier, the total ice volume in 2009 was estimated as 0.061 km(3). Our results indicate that Yala Glacier has lost similar to 40% of its ice volume over the last 27 years and that the rate of the mass loss has accelerated over the last decade

南パタゴニア氷原ペリート・モレノ氷河における熱水掘削

Glaciar Perito Moreno is one of the major freshwater calving glaciers in the Southern Patagonia Icefield. Its fast-flowing characteristic is probably due to high water pressure at the glacier bed, however, subglacial conditions have never been observed in Patagonia until our recent undertaking. To investigate the role of subglacial water pressure in the calving glacier dynamics, we performed hot-water drilling at Glaciar Perito Moreno from February to March 2010. This study represents the first attempt ever at hot-water glacier drilling in Patagonia. Two boreholes were drilled to the bed at 4.7km upglacier from the terminus, where the ice was revealed to be 515±5m thick and the bed located at about 330m below the proglacial lake level. The water levels in the boreholes were >100m above the lake level, which indicates that more than 90% of the ice overburden pressure was balanced out by the subglacial water pressure. Water in the boreholes had drained away before the drilling reached the bed, suggesting the existence of an englacial drainage system. These results provide crucial information for understanding the hydraulic and hydrological conditions of calving glaciers. In order to drill a 500m deep glacier, an existing hot-water drilling system was adapted by increasing the number of high-pressure hot-water machines. The drilling operation at Glaciar Perito Moreno confirmed the system's capacity to drill a 500-m-deep borehole at a rate of 50mh-1 with fuel consumption rates of 15.7lh-1 for diesel and 3.9lh-1 for petrol

Mammalian reverse genetics without crossing reveals Nr3a as a short-sleeper gene

The identification of molecular networks at the system level in mammals is accelerated by next-generation mammalian genetics without crossing, which requires both the efficient production of whole-body biallelic knockout (KO) mice in a single generation and high-performance phenotype analyses. Here, we show that the triple targeting of a single gene using the CRISPR/Cas9 system achieves almost perfect KO efficiency (96%–100%). In addition, we developed a respiration-based fully automated noninvasive sleep phenotyping system, the Snappy Sleep Stager (SSS), for high-performance (95.3% accuracy) sleep/wake staging. Using the triple-target CRISPR and SSS in tandem, we reliably obtained sleep/wake phenotypes, even in double-KO mice. By using this system to comprehensively analyze all of the N-methyl-D-aspartate (NMDA) receptor family members, we found Nr3a as a short-sleeper gene, which is verified by an independent set of triple-target CRISPR. These results demonstrate the application of mammalian reverse genetics without crossing to organism-level systems biology in sleep research

Involvement of Ca2+-dependent hyperpolarization in sleep duration in mammals

The detailed molecular mechanisms underlying the regulation of sleep duration in mammals are still elusive. To address this challenge, we constructed a simple computational model, which recapitulates the electrophysiological characteristics of the slow-wave sleep and awake states. Comprehensive bifurcation analysis predicted that a Ca2+-dependent hyperpolarization pathway may play a role in slow-wave sleep and hence in the regulation of sleep duration. To experimentally validate the prediction, we generate and analyze 21 KO mice. Here we found that impaired Ca2+-dependent K+ channels (Kcnn2 and Kcnn3), voltage-gated Ca2+ channels (Cacna1g and Cacna1h), or Ca2+/calmodulin-dependent kinases (Camk2a and Camk2b) decrease sleep duration, while impaired plasma membrane Ca2+ ATPase (Atp2b3) increases sleep duration. Pharmacological intervention and whole-brain imaging validated that impaired NMDA receptors reduce sleep duration and directly increase the excitability of cells. Based on these results, we propose a hypothesis that a Ca2+-dependent hyperpolarization pathway underlies the regulation of sleep duration in mammals