Impact of Separator Thickness on Temperature Distribution in Single Cell of Polymer Electrolyte Fuel Cell Operated at Higher Temperature of 90 °C and 100 °C

The New Energy and Industry Technology Development Organization (NEDO) road map (Japan, 2017) has proposed that a polymer electrolyte fuel cell (PEFC) system, which operates at a temperature of 90 °C and 100 °C, be applied for stationary and mobility usage, respectively. This study suggests using a thin polymer electrolyte membrane (PEM) and a thin gas diffusion layer (GDL), at the same time, to achieve better power-generation performance, at a higher temperature than usual. The focus of this paper is to clarify the effect of separator thickness on the distribution of temperature at the reaction surface (Treact), with the relative humidity (RH) of the supply gasses and initial operation temperature (Tini), quantitatively. In this study, separator thickness is investigated in a system using a thin PEM and a thin GDL. Moreover, this study investigates the difference between the maximum temperature and the minimum temperature obtained from the distribution of Treact as well as the relation between the standard deviation of Treact − Tini and total voltage, to clarify the effect of separator thickness. The impact of the flow rates of the supply gases on the distribution of Treact is not large, among the investigated conditions. It is noticed that the temperature distribution is wider when a separator thickness of 2.0 mm is selected. On the other hand, it is observed that the temperature increases along with the gas flow through the gas channel, by approximately 2 °C, when using a separator thickness between 1.5 mm and 1.0 mm. The impact of the RH on the distributions of Treact − Tini is larger at Tini = 100 °C, when a separator thickness of 1.0 mm is selected. It is revealed that the wider temperature distribution provides a reduction in power-generation performance. This study proposes that the thin separators, i.e., with a thickness of 1.5 mm and 1.0 mm, are not suitable for higher temperature operation than usual.publishedVersio

Tricalbin proteins regulate plasma membrane phospholipid homeostasis

The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer proteins that function at contacts between the ER and plasma membrane (ER-PM contacts). However, roles of the E-Syt family members in PM lipid organisation remain incomplete. Among the E-Syt family, the yeast tricalbin (Tcb) proteins are essential for PM integrity upon heat stress, but it is not known how they contribute to PM maintenance. Using quantitative lipidomics and microscopy, we find that the Tcb proteins regulate phosphatidylserine homeostasis at the PM. Moreover, upon heat-induced membrane stress, Tcb3 co-localises with the PM protein Sfk1 that is implicated in PM phospholipid asymmetry and integrity. The Tcb proteins also control the PM targeting of the known phosphatidylserine effector Pkc1 upon heat-induced stress. Phosphatidylserine has evolutionarily conserved roles in PM organisation, integrity, and repair. We propose that phospholipid regulation is an ancient essential function of E-Syt family members required for PM integrity

Structure of SARS-CoV-2 membrane protein essential for virus assembly

新型コロナウイルスのウイルス形成に必須の膜タンパク質の構造を解明. 京都大学プレスリリース. 2022-08-08.The coronavirus membrane protein (M) is the most abundant viral structural protein and plays a central role in virus assembly and morphogenesis. However, the process of M protein-driven virus assembly are largely unknown. Here, we report the cryo-electron microscopy structure of the SARS-CoV-2 M protein in two different conformations. M protein forms a mushroom-shaped dimer, composed of two transmembrane domain-swapped three-helix bundles and two intravirion domains. M protein further assembles into higher-order oligomers. A highly conserved hinge region is key for conformational changes. The M protein dimer is unexpectedly similar to SARS-CoV-2 ORF3a, a viral ion channel. Moreover, the interaction analyses of M protein with nucleocapsid protein (N) and RNA suggest that the M protein mediates the concerted recruitment of these components through the positively charged intravirion domain. Our data shed light on the M protein-driven virus assembly mechanism and provide a structural basis for therapeutic intervention targeting M protein

KaPPA-View4: a metabolic pathway database for representation and analysis of correlation networks of gene co-expression and metabolite co-accumulation and omics data

Correlations of gene-to-gene co-expression and metabolite-to-metabolite co-accumulation calculated from large amounts of transcriptome and metabolome data are useful for uncovering unknown functions of genes, functional diversities of gene family members and regulatory mechanisms of metabolic pathway flows. Many databases and tools are available to interpret quantitative transcriptome and metabolome data, but there are only limited ones that connect correlation data to biological knowledge and can be utilized to find biological significance of it. We report here a new metabolic pathway database, KaPPA-View4 (http://kpv.kazusa.or.jp/kpv4/), which is able to overlay gene-to-gene and/or metabolite-to-metabolite relationships as curves on a metabolic pathway map, or on a combination of up to four maps. This representation would help to discover, for example, novel functions of a transcription factor that regulates genes on a metabolic pathway. Pathway maps of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and maps generated from their gene classifications are available at KaPPA-View4 KEGG version (http://kpv.kazusa.or.jp/kpv4-kegg/). At present, gene co-expression data from the databases ATTED-II, COXPRESdb, CoP and MiBASE for human, mouse, rat, Arabidopsis, rice, tomato and other plants are available

Drosophila Carrying Pex3 or Pex16 Mutations Are Models of Zellweger Syndrome That Reflect Its Symptoms Associated with the Absence of Peroxisomes

The peroxisome biogenesis disorders (PBDs) are currently difficult-to-treat multiple-organ dysfunction disorders that result from the defective biogenesis of peroxisomes. Genes encoding Peroxins, which are required for peroxisome biogenesis or functions, are known causative genes of PBDs. The human peroxin genes PEX3 or PEX16 are required for peroxisomal membrane protein targeting, and their mutations cause Zellweger syndrome, a class of PBDs. Lack of understanding about the pathogenesis of Zellweger syndrome has hindered the development of effective treatments. Here, we developed potential Drosophila models for Zellweger syndrome, in which the Drosophila pex3 or pex16 gene was disrupted. As found in Zellweger syndrome patients, peroxisomes were not observed in the homozygous Drosophila pex3 mutant, which was larval lethal. However, the pex16 homozygote lacking its maternal contribution was viable and still maintained a small number of peroxisome-like granules, even though PEX16 is essential for the biosynthesis of peroxisomes in humans. These results suggest that the requirements for pex3 and pex16 in peroxisome biosynthesis in Drosophila are different, and the role of PEX16 orthologs may have diverged between mammals and Drosophila. The phenotypes of our Zellweger syndrome model flies, such as larval lethality in pex3, and reduced size, shortened longevity, locomotion defects, and abnormal lipid metabolisms in pex16, were reminiscent of symptoms of this disorder, although the Drosophila pex16 mutant does not recapitulate the infant death of Zellweger syndrome. Furthermore, pex16 mutants showed male-specific sterility that resulted from the arrest of spermatocyte maturation. pex16 expressed in somatic cyst cells but not germline cells had an essential role in the maturation of male germline cells, suggesting that peroxisome-dependent signals in somatic cyst cells could contribute to the progression of male germ-cell maturation. These potential Drosophila models for Zellweger syndrome should contribute to our understanding of its pathology

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

Impact of Separator Thickness on Temperature Distribution in Single Cell of Polymer Electrolyte Fuel Cell Operated at Higher Temperature of 90 °C and 100 °C

The New Energy and Industry Technology Development Organization (NEDO) road map (Japan, 2017) has proposed that a polymer electrolyte fuel cell (PEFC) system, which operates at a temperature of 90 °C and 100 °C, be applied for stationary and mobility usage, respectively. This study suggests using a thin polymer electrolyte membrane (PEM) and a thin gas diffusion layer (GDL), at the same time, to achieve better power-generation performance, at a higher temperature than usual. The focus of this paper is to clarify the effect of separator thickness on the distribution of temperature at the reaction surface (Treact), with the relative humidity (RH) of the supply gasses and initial operation temperature (Tini), quantitatively. In this study, separator thickness is investigated in a system using a thin PEM and a thin GDL. Moreover, this study investigates the difference between the maximum temperature and the minimum temperature obtained from the distribution of Treact as well as the relation between the standard deviation of Treact − Tini and total voltage, to clarify the effect of separator thickness. The impact of the flow rates of the supply gases on the distribution of Treact is not large, among the investigated conditions. It is noticed that the temperature distribution is wider when a separator thickness of 2.0 mm is selected. On the other hand, it is observed that the temperature increases along with the gas flow through the gas channel, by approximately 2 °C, when using a separator thickness between 1.5 mm and 1.0 mm. The impact of the RH on the distributions of Treact − Tini is larger at Tini = 100 °C, when a separator thickness of 1.0 mm is selected. It is revealed that the wider temperature distribution provides a reduction in power-generation performance. This study proposes that the thin separators, i.e., with a thickness of 1.5 mm and 1.0 mm, are not suitable for higher temperature operation than usual