Algal protein kinase, Triacylglycerol Accumulation Regulator 1, modulates cell viability and gametogenesis in carbon/nitrogen imbalanced conditions

Nutrient-deprived microalgae accumulate triacylglycerol (TAG) in lipid droplets. A dual-specificity tyrosine phosphorylation-regulated kinase, TAG accumulation regulator 1 (TAR1) has been shown to be required for acetate-dependent TAG accumulation and the degradation of chlorophyll and photosynthesis-related proteins in photomixotrophic nitrogen (N)-deficient conditions (Kajikawa et al. 2015). However, this previous report only examined particular condition. Here, we report that in photoautotrophic N-deficient conditions, tar1-1 cells, with a mutation in the TAR1 gene, maintained higher levels of cell viability and lower levels of hydrogen peroxide generation and accumulated higher levels of TAG and starch compared with those of wild-type (WT) cells with bubbling of air containing 5% carbon dioxide. Transcriptomic analyses suggested that genes involved in the scavenging of reactive oxygen species are not repressed in tar1-1 cells. In contrast, the mating efficiency and mRNA levels of key regulatory genes for gametogenesis, MID, MTD, and FUS, were suppressed in tar1-1 cells. Among the TAR1-dependent phosphopeptides deduced by phosphoproteomic analysis, protein kinases and enzymes related to N assimilation and carbon (C) metabolism are of particular interest. Characterization of these putative downstream factors may elucidate the molecular pathway whereby TAR1 mediates cellular propagation and C and N metabolism in C/N-imbalanced stress conditions

The potential role of temperate Japanese regions as refugia for the coral Acropora hyacinthus in the face of climate change

As corals in tropical regions are threatened by increasing water temperatures, poleward range expansion of reef-building corals has been observed, and temperate regions are expected to serve as refugia in the face of climate change. To elucidate the important indicators of the sustainability of coral populations, we examined the genetic diversity and connectivity of the common reef-building coral Acropora hyacinthus along the Kuroshio Current, including recently expanded (<50 years) populations. Among the three cryptic lineages found, only one was distributed in temperate regions, which could indicate the presence of Kuroshio-associated larval dispersal barriers between temperate and subtropical regions, as shown by oceanographic simulations as well as differences in environmental factors. The level of genetic diversity gradually decreased towards the edge of the species distribution. This study provides an example of the reduced genetic diversity in recently expanded marginal populations, thus indicating the possible vulnerability of these populations to environmental changes. This finding underpins the importance of assessing the genetic diversity of newly colonized populations associated with climate change for conservation purposes. In addition, this study highlights the importance of pre-existing temperate regions as coral refugia, which has been rather underappreciated in local coastal management

Prominent IgM Deposition in Glomerulus Is Associated with Severe Proteinuria and Reduced after Combined Treatment of Tonsillectomy with Steroid Pulse Therapy in Patients with IgA Nephropathy

IgA nephropathy (IgAN) is characterized by mesangial deposition of IgA, C3, and often IgM. We examined the relationship among IgM deposition, clinical features, and renal outcome in IgAN patients who underwent combined treatment of tonsillectomy with steroid pulse therapy (Tx-SP). We retrospectively reviewed 73 IgAN patients treated with Tx-SP from March 2006 to March 2014. The patients were divided into those with moderate (2+) to severe (3+) mesangial IgM deposition (Prominent IgM-positive patients, P-Group) and those with negative (−) to faint (1+) deposition (the “Other” patients, O-Group). Using propensity scores to minimize confounding factors, 11 propensity score-matched patients with O-Group (mO-Group) were compared to 11 P-Group patients. The study outcome was defined as urinary protein grade by urine test strip before Tx-SP and one year after Tx-SP. P-Group patients exhibited an increased severity of proteinuria compared to O-Group (p=0.018) and mO-Group patients (p=0.009) before Tx-SP. After Tx-SP, proteinuria was significantly ameliorated in the P-Group, reaching the same severity recorded in the O-Group (p=0.007) and mO-Group (p=0.021). No significant differences were noted between P-Group and mO-Group in microhematuria, serum creatinine level, and histological severity. Prominent IgM deposition is associated with severe proteinuria in IgAN. However, Tx-SP induces a sufficient reduction in the severity of proteinuria in IgM-positive IgAN

TDP-43 stabilises the processing intermediates of mitochondrial transcripts

The 43-kDa trans-activating response region DNA-binding protein 43 (TDP-43) is a product of a causative gene for amyotrophic lateral sclerosis (ALS). Despite of accumulating evidence that mitochondrial dysfunction underlies the pathogenesis of TDP-43–related ALS, the roles of wild-type TDP-43 in mitochondria are unknown. Here, we show that the small TDP-43 population present in mitochondria binds directly to a subset of mitochondrial tRNAs and precursor RNA encoded in L-strand mtDNA. Upregulated expression of TDP-43 stabilised the processing intermediates of mitochondrial polycistronic transcripts and their products including the components of electron transport and 16S mt-rRNA, similar to the phenotype observed in cells deficient for mitochondrial RNase P. Conversely, TDP-43 deficiency reduced the population of processing intermediates and impaired mitochondrial function. We propose that TDP-43 has a novel role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts

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

口臭と胃内ヘリコバクタピロリ感染との関連

口臭の原因は,ほとんどが口腔内の舌苔や歯周病に起因し,その主な原因ガスは揮発性硫黄化合物(VSCs)だと言われている.胃内ヘリコバクタピロリ感染も口臭の一因であるとする報告がなされたが,VSCsを定性・定量的に測定した研究はない.この研究の目的は,胃内ヘリコバクタピロリ感染の陽性者群と陰性者群の口臭と舌苔臭を官能試験およびガスクロマトグラフィによるVSCsの測定を用いて比較することである.また,両群の背景因子として,年齢,性別,口臭に関連すると考えられる口腔内パラメーター(歯垢指数,歯肉炎指数,4mm以上の歯周ポケット数,出血歯周ポケット数,視診による舌苔スコア,舌苔重量)を検討した.80名の患者のうち,胃内ヘリコバクタピロリ感染の陽性者は31名(平均44.7歳)で,陰性者は49名(平均33.8歳)であった.年齢は陽性者の方が有意に高かったが,性別比や口腔内パラメーターなどの背景因子には差を認めなかった.口臭の官能試験では,息をとめた状態の口臭に有意差を認め(オッズ比:2.76,95%信頼区間:1.78～3.74),胃内ヘリコバクタピロリ感染の陽性者の方が陰性者に比較して口臭は臭いことが確認された.しかし,息を吐いた状態の口臭および舌苔臭には両群間に差を認めなかった.ガスクロマトグラフイによるVSCsの測定では,メチルメルカプタンに差を認めなかったが,硫化水素とジメチルサルファイドに有意差(p<0.05)を認めた.今後,胃内ヘリコバクタピロリ感染と口臭との関連について,さらに検討が必要である.The aim of the present study was to assess whether oral odour and tongue coating odour in the gastric Helicobacter pylori (H. pylori) positive patients are more severe organoleptically than those of the negative patients. Moreover, this is the first study of halitosis on H. pylori in which qualitative-quantitative measurements were made by gas chromatography (GC). In addition, the backgrounds (age, gender, oral periodontal parameters and tongue coating) were compared between the 31 H. pylori positive and 49 negative patients. The H. pylori positive group was significantly older than the H. pylori negative group. There were no significant differences in gender, periodontal parameters or visual tongue coating assessment between the two groups. The oral odour assessed with patient holding breath by organoleptic measurement, the gastric H. pylori positive patients was more severe than that of the negative patients (Odds ratio: 2.76, 95% CI: 1.78 to 3.74). There were no significant differences in oral odour assessed with patient exhaling breath and tongue coating odour. The levels of H_2S and (CH_3)_2S but not CH_3SH, in oral air measured by GC were significantly higher in the H. pylori positive patients than in the negative patients (p<0.05). Further research confirming the relation between gastric H. pylori infection and halitosis is needed

口臭と胃内ヘリコバクタピロリ感染との関連

口臭の原因は,ほとんどが口腔内の舌苔や歯周病に起因し,その主な原因ガスは揮発性硫黄化合物(VSCs)だと言われている.胃内ヘリコバクタピロリ感染も口臭の一因であるとする報告がなされたが,VSCsを定性・定量的に測定した研究はない.この研究の目的は,胃内ヘリコバクタピロリ感染の陽性者群と陰性者群の口臭と舌苔臭を官能試験およびガスクロマトグラフィによるVSCsの測定を用いて比較することである.また,両群の背景因子として,年齢,性別,口臭に関連すると考えられる口腔内パラメーター(歯垢指数,歯肉炎指数,4mm以上の歯周ポケット数,出血歯周ポケット数,視診による舌苔スコア,舌苔重量)を検討した.80名の患者のうち,胃内ヘリコバクタピロリ感染の陽性者は31名(平均44.7歳)で,陰性者は49名(平均33.8歳)であった.年齢は陽性者の方が有意に高かったが,性別比や口腔内パラメーターなどの背景因子には差を認めなかった.口臭の官能試験では,息をとめた状態の口臭に有意差を認め(オッズ比:2.76,95%信頼区間:1.78～3.74),胃内ヘリコバクタピロリ感染の陽性者の方が陰性者に比較して口臭は臭いことが確認された.しかし,息を吐いた状態の口臭および舌苔臭には両群間に差を認めなかった.ガスクロマトグラフイによるVSCsの測定では,メチルメルカプタンに差を認めなかったが,硫化水素とジメチルサルファイドに有意差(p<0.05)を認めた.今後,胃内ヘリコバクタピロリ感染と口臭との関連について,さらに検討が必要である.The aim of the present study was to assess whether oral odour and tongue coating odour in the gastric Helicobacter pylori (H. pylori) positive patients are more severe organoleptically than those of the negative patients. Moreover, this is the first study of halitosis on H. pylori in which qualitative-quantitative measurements were made by gas chromatography (GC). In addition, the backgrounds (age, gender, oral periodontal parameters and tongue coating) were compared between the 31 H. pylori positive and 49 negative patients. The H. pylori positive group was significantly older than the H. pylori negative group. There were no significant differences in gender, periodontal parameters or visual tongue coating assessment between the two groups. The oral odour assessed with patient holding breath by organoleptic measurement, the gastric H. pylori positive patients was more severe than that of the negative patients (Odds ratio: 2.76, 95% CI: 1.78 to 3.74). There were no significant differences in oral odour assessed with patient exhaling breath and tongue coating odour. The levels of H_2S and (CH_3)_2S but not CH_3SH, in oral air measured by GC were significantly higher in the H. pylori positive patients than in the negative patients (p<0.05). Further research confirming the relation between gastric H. pylori infection and halitosis is needed

Correction to: Association between NAT2, CYP1A1, and CYP1A2 genotypes, heterocyclic aromatic amines, and prostate cancer risk: a case control study in Japan

Following publication of the original article [1], the authors reported a correction in the units in the methods section under “Subjects

High phosphorylation of HBV core protein by two α-type CK2-activated cAMP-dependent protein kinases in vitro

AbstractTwo α-type CK2-activated PKAs (CK2-aPKAIα and CK2-aPKAIIα) were biochemically characterized in vitro using GST-HBV core fusion protein (GST-Hcore) and GST-Hcore157B as phosphate acceptors. It was found that (i), in the absence of cAMP, these two CK2-aPKAs phosphorylated both Ser-170 and Ser-178 on GST-Hcore and Hcore157B; (ii) this phosphorylation was approx. 4-fold higher than their phosphorylation by cAMP-activated PKAs; and (iii) suramin effectively inhibited the phosphorylation of Hcore157B by CK2-aPKAIIα through its direct binding to Hcore157B in vitro. These results suggest that high phosphorylation of HBV-CP by two CK2-aPKAs, in the absence of cAMP, may be involved in the pregenomic RNA (pgRNA) encapsidation and DNA-replication in HBV-infected cells