Milk product intake, muscle strength, and NFKB methylation

Background Muscle atrophy with aging is closely associated with chronic systemic inflammation and lifestyle-related diseases. In the present study, we assessed whether post-exercise milk product intake during 5-month interval walking training (IWT) enhanced the increase in thigh muscle strength and ameliorated susceptibility to inflammation in older women. Methods Subjects [n = 37, 66±5 (standard deviation) yrs] who had been performing IWT for >6 months participated in this study. They were randomly divided into the following 3 groups: IWT alone (CNT, n = 12), IWT + low-dose post-exercise milk product intake (LD, n = 12; 4 g protein and 3 g carbohydrate) or IWT + a 3-times higher dose of milk product intake than the LD group (HD, n = 13). They were instructed to repeat ≥5 sets of fast and slow walking for 3 min each at ≥70% and 40% peak aerobic capacity for walking, respectively, per day for ≥4 days/week. Results After IWT, thigh muscle strength increased in the HD group (8±2%) more than in the CNT group (-2±3%, P = 0.022), despite similar IWT achievements between the groups (P>0.15). Pyrosequencing analysis using whole blood showed that methylation of NFKB1 and NFKB2, master genes of inflammation, was enhanced in the HD group (29±7% and 44 ±11%, respectively) more than in the CNT group (-20±6% and -10±6%, respectively; P<0.001). Moreover, the genome-wide DNA methylation analysis showed that several inflammation-related genes were hyper-methylated in the HD group compared with that in the CNT group, suggesting greater pro-inflammatory cytokine gene suppression in the HD group. Conclusion HD milk product intake after exercise produced a greater percent increase in thigh muscle strength and NFKB1 and NFKB2 gene methylation during IWT in physically active older women

Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals

Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci (P<5 × 10–8) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci—TMEM18, TM4SF4, MXD3-LMAN2, PSORS1C1-PSORS1C2, and HNF4A—are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578, is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout

Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout

Objective The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout. Methods We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia). Results This new approach enabled us to identify two novel gout loci (rs7927466 of CNTN5 and rs9952962 of MIR302F) and one suggestive locus (rs12980365 of ZNF724) at the genome-wide significance level (p<5.0×10– 8). The present study also identified the loci of ABCG2, ALDH2 and SLC2A9. One of them, rs671 of ALDH2, was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three ‘gout vs AHUA GWAS’-specific loci (CNTN5, MIR302F and ZNF724) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level. Conclusions This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals

ショウガイジ オ モツ ハハオヤ ノ セイシンテキ ケンコウド 2 ニュウヨウジキ ト ガクレイキ ノ ヒカク

本研究の目的は、障害児を持つ母親の精神的健康度の現状を明らかにし、必要な支援内容に関する指針を得ることである。 対象者はE県の通園事業・通園施設を利用する乳幼児の母親247名とE県立養護学校に通学する児童を持つ母親98名である。母親の属性(年齢、就労状況、世帯構造等)と、「育児ストレス・コーピング」、「育児バーンアウト」、「孤独感」について調査し分析した。さらに、同研究(I)で明らかにした他の指標(「母親の健康関連QOL」「育児ソーシャルサポート」「父親の育児サポート認知」「育児負担感」)との関連性について分析した。また、乳幼児と児童の母親の違いについて分析し、障害児を持つ母親の精神的健康度を高めるための示唆を得た。 障害児を持つ母親の健康関連QOLを高めるためには、乳幼児を持つ母親の場合、育児ソーシャルサポートが逃避的コーピングを回避し、さらに父親の育児サポートが調整的コーピング行動を惹起し、育児負担感や、育児バーンアウト、孤独感を抑制することが示された。一方、児童の母親の場合は健康関連QOLと育児ソーシャルサポートや、父親の育児サポートとは直接的な関連性がないことが明らかになった。しかし、育児負担感や育児バーンアウト、孤独感とは強い相関が認められた。また、育児負担感を軽減し育児バーンアウトを抑制するためには、父親の育児サポートが大きな要因となっていることが明らかになった。また、孤独感は児童の母親の場合は全ての尺度と関連があったが、乳幼児の場合は、父親のサポート認知とは関連が認められないという違いが見られた。The purpose of this study is to investigate condition of mental health on mothers who have disabled preschool/school age children and to provide useful information for developing the assistance guideline for them. 247 mothers who utilize nursery schools for the disabled and 98 mothers who use schools for the disabled attended this study. Questionnaire was consisted of attributes of mothers (age, employment condition, family structure), coping type to parenting stress, parenting burnout, and loneliness. After analyzing these data, following findings were found. For mothers who have preschool disabled children, parenting-related social supports prevented their negative coping (i.e. escape). And parenting support from fathers reduce their parenting stress, parenting burnout and loneliness. For mothers who have school age disabled children, parenting-related social support and parenting support from fathers do not have positive influences on their condition of mental health

ショウガイジ オ モツ ハハオヤ ノ セイシンテキ ケンコウド 1 ニュウヨウジキ ト ガクレイキ ノ ヒカク

本研究の目的は、障害児を持つ母親の精神的健康度の現状を明らかにし、必要な支援内容に関する指針を得ることである。 対象者はE県の通園事業、通園施設を利用する乳幼児の母親247名とE県立養護学校に通学する児童を持つ母親98名である。母親の属性(年齢、就労状況、世帯構造等)と子どもの属性(年齢、性、障害の種類と程度)および「母親の健康関連QOL」、「育児ソーシャルサポート」、母親による「父親の育児サポート認知」、「育児負担感」を調査し分析した。さらに乳幼児と児童の母親の違いについて考察した。 その結果、障害児を持つ母親のQOLを高めるためには、母親の育児負担感を軽減する必要があることが示された。また、児童の母親にとっては父親の育児サポートが育児負担感を軽減することが示唆された。乳幼児の母親のQOLは、育児ソーシャルサポート、父親のサポートによって高められることが示された。The purpose of this study is to examine the level of mental health of mothers with disabled children in order to develop guidelines for the assistance necessary to help them. The subjects were 247 mothers with disabled infants utilizing the institutes of nursery schools for disabled infants in E prefecture and 98 mothers of disabled children attending an E prefectural school for the disabled. This study examined and analyzed the attributes of mothers (age, employment status and household structure), the attributes of children (age, sex, and degree and kind of disability),the quality of life (QOL) of mothers, the social support for raising children, the level of support from fathers, and the parenting stress of mother. This study also examined the difference between mothers of children and those of infants. The results of this study indicate that to increase the QOL of mothers, parenting stress of mother need to be reduced. Moreover, this study suggests that the QOL of mothers be improved by the support of fathers and the social support for raising disabled children

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

Hydrocarbon Cycling in the Tokamachi Mud Volcano (Japan): Insights from Isotopologue and Metataxonomic Analyses

Understanding hydrocarbon cycling in the subsurface is important in various disciplines including climate science, energy resources and astrobiology. Mud volcanoes provide insights into biogeochemical processes occurring in the subsurface. They are usually associated with natural gas reservoirs consisting mainly of methane and other hydrocarbons as well as CO2. Stable isotopes have been used to decipher the sources and sinks of hydrocarbons in the subsurface, although the interpretation can be ambiguous due to the numerous processes involved. Here we report new data for hydrocarbon isotope analysis, including position-specific isotope composition of propane, for samples from the Tokamachi mud volcano area, Japan. The data suggest that C2+ hydrocarbons are being biodegraded, with indirect production of methane (&ldquo;secondary methanogenesis&rdquo;). Data from chemical and isotopic composition are discussed with regard to 16S rRNA analysis, which exhibits the presence of hydrogenotrophic and acetoclastic methoanogens. Overall, the combination of isotopologue analysis with 16S rRNA gene data allows refining of our understanding of hydrocarbon cycling in subsurface environments

Discrimination of object information by bat echolocation deciphered from acoustic simulations

High-precision visual sensing has been achieved by combining cameras with deep learning. However, an unresolved challenge involves identifying information that remains elusive for optical sensors, such as occlusion spots hidden behind objects. Compared to light, sound waves have longer wavelengths and can, therefore, collect information on occlusion spots. In this study, we investigated whether bats could perform advanced sound sensing using echolocation to acquire a target's occlusion information. We conducted a two-alternative forced choice test on Pipistrellus abramus with five different targets, including targets with high visual similarity from the front, but different backend geometries, i.e. occlusion spots or textures. Subsequently, the echo impulse responses produced by these targets, which were difficult to obtain with real measurements, were computed using three-dimensional acoustic simulations to provide a detailed analysis consisting of the acoustic cues that the bats obtained through echolocation. Our findings demonstrated that bats could effectively discern differences in target occlusion spot structure and texture through echolocation. Furthermore, the discrimination performance was related to the differences in the logarithmic spectral distortion of the occlusion-related components in the simulated echo impulse responses. This suggested that the bats obtained occlusion information through echolocation, highlighting the advantages of utilizing broadband ultrasound for sensing

Effect of light wavelength on hot spring microbial mat biodiversity

<div><p>Hot spring associated phototrophic microbial mats are purely microbial communities, in which phototrophic bacteria function as primary producers and thus shape the community. The microbial mats at Nakabusa hot springs in Japan harbor diverse photosynthetic bacteria, mainly <i>Thermosynechococcus</i>, <i>Chloroflexus</i>, and <i>Roseiflexus</i>, which use light of different wavelength for energy conversion. The aim of this study was to investigate the effect of the phototrophs on biodiversity and community composition in hot spring microbial mats. For this, we specifically activated the different phototrophs by irradiating the mats with different wavelengths in situ. We used 625, 730, and 890 nm wavelength LEDs alone or in combination and confirmed the hypothesized increase in relative abundance of different phototrophs by 16S rRNA gene sequencing. In addition to the increase of the targeted phototrophs, we studied the effect of the different treatments on chemotrophic members. The specific activation of <i>Thermosynechococcus</i> led to increased abundance of several other bacteria, whereas wavelengths specific to <i>Chloroflexus</i> and <i>Roseiflexus</i> induced a decrease in >50% of the community members as compared to the dark conditions. This suggests that the growth of <i>Thermosynechococcus</i> at the surface layer benefits many community members, whereas less benefit is obtained from an increase in filamentous anoxygenic phototrophs <i>Chloroflexus</i> and <i>Roseiflexus</i>. The increases in relative abundance of chemotrophs under different light conditions suggest a relationship between the two groups. Aerobic chemoheterotrophs such as <i>Thermus</i> sp. and <i>Meiothermus sp</i>. are thought to benefit from aerobic conditions and organic carbon in the form of photosynthates by <i>Thermosynechococcus</i>, while the oxidation of sulfide and production of elemental sulfur by filamentous anoxygenic phototrophs benefit the sulfur-disproportionating <i>Caldimicrobium thiodismutans</i>. In this study, we used an experimental approach under controlled environmental conditions for the analysis of natural microbial communities, which proved to be a powerful tool to study interspecies relationships in the microbiome.</p></div