Host Associations, Phylogenetics, and Biogeography of Parasitic Avian Chewing Lice (Insecta: Phthiraptera) from Sub-Saharan Africa

Parasitic chewing lice (Insecta: Phthiraptera) of birds are found everywhere their avian hosts are distributed, and their host relationships and taxonomy have been well studied in many regions. Lice have obligate parasitic relationships with their hosts (entire life cycle is carried out on the host body) and generally undergo vertical transmission across host generations. These biological traits of lice make them excellent model systems for exploring host-parasite co-evolution. Compared with Europe and the Americas, the ectoparasite fauna of Sub-Saharan African birds is poorly understood despite the avian fauna being relatively well-known. Recent field expeditions exploring the avian diversity in South Africa, Benin, and the Democratic Republic of the Congo allow an opportunity to obtain louse specimens from across Sub-Saharan Africa. The goal of this study was to investigate avian louse host associations and genetic diversity to increase our understanding of southern African parasite biodiversity, as well as to use molecular phylogenetic methods to examine potential broad biogeographic patterns in lice across Sub-Saharan Africa. From 1105 South African bird individuals and 170 species examined for lice, a total of 104 new louse-host associations were observed. Portions of the mitochondrial COI and nuclear EF-1α genes were amplified to observe phylogenetic relationships of southern African lice and investigate potential new species. The phylogenetic results gave strong support for multiple louse genera, and 26 genetically unique lineages were found, which may represent new louse species. Examining biogeographic patterns in parasitic lice across the entire region of Sub-Saharan Africa indicated that lice tend to follow host distributions rather than grouping by geographic region. Several promising louse taxa were identified as candidates for future phylogenetic and biogeographic studies investigating Sub-Saharan African chewing lice

Host Associations, Phylogenetics, and Biogeography of Parasitic Avian Chewing Lice (Insecta: Phthiraptera) from Sub-Saharan Africa

Parasitic chewing lice (Insecta: Phthiraptera) of birds are found everywhere their avian hosts are distributed, and their host relationships and taxonomy have been well studied in many regions. Lice have obligate parasitic relationships with their hosts (entire life cycle is carried out on the host body) and generally undergo vertical transmission across host generations. These biological traits of lice make them excellent model systems for exploring host-parasite co-evolution. Compared with Europe and the Americas, the ectoparasite fauna of Sub-Saharan African birds is poorly understood despite the avian fauna being relatively well-known. Recent field expeditions exploring the avian diversity in South Africa, Benin, and the Democratic Republic of the Congo allow an opportunity to obtain louse specimens from across Sub-Saharan Africa. The goal of this study was to investigate avian louse host associations and genetic diversity to increase our understanding of southern African parasite biodiversity, as well as to use molecular phylogenetic methods to examine potential broad biogeographic patterns in lice across Sub-Saharan Africa. From 1105 South African bird individuals and 170 species examined for lice, a total of 104 new louse-host associations were observed. Portions of the mitochondrial COI and nuclear EF-1α genes were amplified to observe phylogenetic relationships of southern African lice and investigate potential new species. The phylogenetic results gave strong support for multiple louse genera, and 26 genetically unique lineages were found, which may represent new louse species. Examining biogeographic patterns in parasitic lice across the entire region of Sub-Saharan Africa indicated that lice tend to follow host distributions rather than grouping by geographic region. Several promising louse taxa were identified as candidates for future phylogenetic and biogeographic studies investigating Sub-Saharan African chewing lice

Phanerochaete crassa WD1694株の未晒クラフトパルプ漂白とリグニン分解酵素に関する研究

学位の種別: 論文博士審査委員会委員 : （主査）東京大学教授 松本 雄二, 東京大学教授 鮫島 正浩, 東京大学准教授 五十嵐 圭日子, 東京大学准教授 横山 朝哉, 森林総合研究所研究ディレクター 眞柄 謙吾University of Tokyo(東京大学

Risk Factors for Infection in Patients with Remitted Rheumatic Diseases Treated with Glucocorticoids

It is well known that infection is one of the major causes of morbidity and mortality in rheumatic disease patients treated with high-dose glucocorticoids, especially in the early phase after achievement of disease remission. The aim of this study was to identify the risk factors for infection, with a focus on the dose of glucocorticoids administered, following the achievement of disease remission in rheumatic diseases patients. We retrospectively analyzed the medical records of rheumatic disease patients who had been treated with glucocorticoids. The primary endpoint was the incidence rate of infection during a period from 1 to 2 months after the commencement of treatment. From April 2006 to March 2010, 19 of 92 patients suffered from infection during the observation period. Age≧65 yrs, presence of interstitial pneumonia, diagnosis of systemic vasculitis and serum creatinine level≧2.0mg/dl were found to be univariate predictors for infection. However, only the presence of interstitial pneumonia was an independent risk factor for infection (HR＝4.50, 95%CI＝1.65 to 14.44) by the Cox proportional hazard model. Even after achievement of clinical remission, careful observation is needed for patients with interstitial pneumonia, more so than for those receiving high-dose glucocorticoids

Inhibitors of ABCB1 and ABCG2 overcame resistance to topoisomerase inhibitors in small cell lung cancer

博士（医学）甲日本医科大学202

Peroxisome proliferator-activated receptor activity is involved in the osteoblastic differentiation regulated by bone morphogenetic proteins and tumor necrosis factor-α.

Recent studies have suggested possible adverse effects of thiazolidinediones on bone metabolism. However, the detailed mechanism by which the activity of PPAR affects bone formation has not been elucidated. Impaired osteoblastic function due to cytokines is critical for the progression of inflammatory bone diseases. In the present study, we investigated the cellular mechanism by which PPAR actions interact with osteoblast differentiation regulated by BMP and TNF-alpha using mouse myoblastic C2C12 cells. BMP-2 and -4 potently induced the expression of various bone differentiation markers including Runx2, osteocalcin, type-1 collagen and alkaline phosphatase (ALP) in C2C12 cells. When administered in combination with a PPAR alpha agonist (fenofibric acid) but not with a PPAR gamma agonist (pioglitazone), BMP-4 enhanced osteoblast differentiation through the activity of PPAR alpha. The osteoblastic changes induced by BMP-4 were readily suppressed by treatment with TNF-alpha. Interestingly, the activities of PPAR alpha and PPAR gamma agonists reversed the suppression by TNF-alpha of osteoblast differentiation induced by BMP-4. Furthermore, TNF-alpha-induced phosphorylation of MAPKs, NF kappa B, I kappa B and Stat pathways was inhibited in the presence of PPAR alpha and PPAR gamma agonists with reducing TNF-alpha receptor expression. In view of the finding that inhibition of SAPK/JNK. Stat and NF kappa B pathways reversed the TNF-alpha suppression of osteoblast differentiation, we conclude that these cascades are functionally involved in the actions of PPARs that antagonize TNF-alpha-induced suppression of osteoblast differentiation. It was further discovered that the PPAR alpha agonist enhanced BMP-4-induced Smad1/5/8 signaling through downregulation of inhibitory Smad6/7 expression, whereas the PPAR gamma agonist impaired this activity by suppressing BMPRII expression. On the other hand, BMPs increased the expression levels of PPAR alpha and PPAR gamma in the process of osteoblast differentiation. Thus, PPAR alpha actions promote BMP-induced osteoblast differentiation, while both activities of PPAR alpha and PPAR gamma suppress TNF-alpha actions. Collectively, our present data establishes that PPAR activities are functionally involved in modulating the interaction between the BMP system and TNF-alpha receptor signaling that is crucial for bone metabolism

Association of glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS): a cross-sectional study

Background While survival of systemic lupus erythematosus (SLE) patients has improved substantially, problems remain in the management of their emotional health. Medium to high-dose glucocorticoid doses are known to worsen emotional health; the effect is unclear among patients receiving relatively low-dose glucocorticoids. This study aims to investigate the association between low glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS). Methods This cross-sectional study drew on data from SLE patients in 10 Japanese institutions. The participants were adult patients with SLE duration of >= 1 year who met LLDAS criteria at the study visit from April 2018 through September 2019. The exposure was the daily glucocorticoid dose (mg oral prednisolone). The outcome was the emotional health score of the lupus patient-reported outcome scale (range: 0 to 100). Multiple linear regression analysis was performed with adjustment for confounders including disease-related damage, activity, and psychotropic drug use. Results Of 192 patients enrolled, 175 were included in the analysis. Their characteristics were as follows: female, 89.7%; median age, 47 years (interquartile range (IQR): 37.0, 61.0). Median glucocorticoid dose was 4.0 mg (IQR 2.0, 5.0), and median emotional health score 79.2 (IQR 58.3, 91.7). Multiple linear regression analysis showed daily glucocorticoid doses to be associated with worse emotional health (beta coefficient = - 2.54 [95% confidence interval - 4.48 to - 0.60], P = 0.01). Conclusions Daily glucocorticoid doses were inversely associated with emotional health among SLE patients in LLDAS. Further studies are needed to determine whether glucocorticoid tapering leads to clinically significant improvements in emotional health

Low incidence of limb-girdle muscular dystrophy type 2C revealed by a mutation study in Japanese patients clinically diagnosed with DMD

<p>Abstract</p> <p>Background</p> <p>Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD). Although DMD is known to affect one in every 3500 males regardless of race, a widespread founder mutation causing LGMD2C has been described in North Africa. However, the incidence of LGMD2C in Japanese has been unknown because the genetic background remains uncharacterized in many patients clinically diagnosed with DMD.</p> <p>Methods</p> <p>We enrolled 324 patients referred to the Kobe University Hospital with suspected DMD. Mutations in the dystrophin or the SGCG genes were analyzed using not only genomic DNA but also cDNA.</p> <p>Results</p> <p>In 322 of the 324 patients, responsible mutations in the dystrophin were successfully revealed, confirming DMD diagnosis. The remaining two patients had normal dystrophin expression but absence of γ-sarcoglycan in skeletal muscle. Mutation analysis of the SGCG gene revealed homozygous deletion of exon 6 in one patient, while the other had a novel single nucleotide insertion in exon 7 in one allele and deletion of exon 6 in the other allele. These mutations created a stop codon that led to a γ-sarcoglycan deficiency, and we therefore diagnosed these two patients as having LGMD2C. Thus, the relative incidence of LGMD2C among Japanese DMD-like patients can be calculated as 1 in 161 patients suspected to have DMD (2 of 324 patients = 0.6%). Taking into consideration the DMD incidence for the overall population (1/3,500 males), the incidence of LGMD2C can be estimated as 1 per 560,000 or 1.8 per million.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first study to demonstrate a low incidence of LGMD2C in the Japanese population.</p

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