Inhibition of c-Jun NH2-terminal kinase activity improves ischemia/reperfusion injury in rat lungs

Although c-Jun NH 2 -terminal kinase (JNK) has been implicated in the pathogenesis of transplantation-induced ischemia/reperfusion (I/R) injury in various organs, its significance in lung transplantation has not been conclusively elucidated. We therefore attempted to measure the transitional changes in JNK and AP-1 activities in I/R-injured lungs. Subsequently, we assessed the effects of JNK inhibition by the three agents including SP600125 on the degree of lung injury assessed by means of various biological markers in bronchoalveolar lavage fluid and histological examination including detection of apoptosis. In addition, we evaluated the changes in p38, extracellular signal-regulated kinase, and NF-B-DNA binding activity. I/R injury was established in the isolated rat lung preserved in modified Euro-Collins solution at 4°C for 4 h followed by reperfusion at 37°C for 3 h. We found that AP-1 was transiently activated during ischemia but showed sustained activation during reperfusion, leading to significant lung injury and apoptosis. The change in AP-1 was generally in parallel with that of JNK, which was activated in epithelial cells (bronchial and alveolar), alveolar macrophages, and smooth muscle cells (bronchial and vascular) on immunohistochemical examination. The change in NF-B qualitatively differed from that of AP-1. Protein leakage, release of lactate dehydrogenase and TNF-␣ into bronchoalveolar lavage fluid, and lung injury were improved, and apoptosis was suppressed by JNK inhibition. In conclusion, JNK plays a pivotal role in mediating lung injury caused by I/R. Therefore, inhibition of JNK activity has potential as an effective therapeutic strategy for preventing I/R injury during lung transplantation

ザイタク デ ニンチショウ ノ ヒト オ カイゴ スル ダンセイ ノ カイゴ モンダイ タイショ スタイル ノ サンシュツ ホウホウ

男性介護者の介護問題対処スタイルの算出方法を明らかにすることを目的とした．対象者は男性介護者298 名である．対処スタイルの平均得点と標準偏差，寄与率による各対処スタイルの独立性の検討と，基準関連法による各対処スタイルの妥当性を検討した．結果・考察: 平均得点と標準偏差，寄与率から似た特徴を持つ対処スタイルであることが考えられたが，基準関連法により独立した対処スタイルであることが明らかとなり，各対処スタイルは独立した特徴を持つことが明らかとなった．男性の介護問題対処の算出方法は，各対処スタイルの平均得点とし，最も得点が高い対処スタイルが，介護問題へ活用する対処であると考えられる．The purpose of this paper was to calculation of the coping scale for Nursing Care Problems Coping Scale for Male Caregivers for People with Dementia Living at Home. The subjects were 298 men who care for people with dementia at home. It was independence and investigated validity the coping style; the result of av erage score, standard deviation and Contribution ratio of coping style. Each coping styles are independent, it became clear that each with its own characteristics. Calculation method is the average score of each coping style. Most high score of average of coping style is the coping style of nursing care problem.原著論文 = Original articl

Attentional Set-Shifting Deficit in Parkinson’s Disease Is Associated with Prefrontal Dysfunction: An FDG-PET Study

The attentional set-shifting deficit that has been observed in Parkinson’s disease (PD) has long been considered neuropsychological evidence of the involvement of meso-prefrontal and prefrontal-striatal circuits in cognitive flexibility. However, recent studies have suggested that non-dopaminergic, posterior cortical pathologies may also contribute to this deficit. Although several neuroimaging studies have addressed this issue, the results of these studies were confounded by the use of tasks that required other cognitive processes in addition to set-shifting, such as rule learning and working memory. In this study, we attempted to identify the neural correlates of the attentional set-shifting deficit in PD using a compound letter task and 18F-fluoro-deoxy-glucose (FDG) positron emission tomography during rest. Shift cost, which is a measure of attentional set-shifting ability, was significantly correlated with hypometabolism in the right dorsolateral prefrontal cortex, including the putative human frontal eye field. Our results provide direct evidence that dysfunction in the dorsolateral prefrontal cortex makes a primary contribution to the attentional set-shifting deficit that has been observed in PD patients

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

Piezoresistive properties of carbon nanotubes under radial force investigated by atomic force microscopy

We investigated the piezoresistive properties of single-wall carbon nanotubes (SWCNTs) under the tip-induced force in the radial direction using atomic force microscopy. We found that the conductance of the bundled SWCNTs was modulated by the applied radial force. The polarity and amount of the conductance change were different on every bundle and even dependent on the location where the force was applied. These phenomena were explained by the modulation of the band structures of the SWCNTs, which was caused by the deformation at the critical pressure

Magnetic torque and heat capacity measurements on TPP[Fe(Pc)(CN)2]2

Magnetic torque and heat capacity measurements on TPP[Fe(Pc)(CN)2]2 are reported. The torque curves for the magnetic field rotated within the ab plane have a fourfold symmetry, exhibiting inversions around 13 and 27K. The heat capacity exhibits a broad peak around T=16.5K. By applying the magnetic field along the c axis, the maximum value of the heat capacity is enhanced below 20K. These results, as well as the magnetic susceptibility, were analyzed by employing a numerical calculation based on the anisotropic Heisenberg model in one dimension. The analyses revealed that: (i) the peak in the magnetic-susceptibility data around 25K is due to an antiferromagnetic short-range order (SRO) formation associated with d electrons, and (ii) π electrons fall into an antiferromagnetic state below 13K. The spin-flop field of π electrons is approximately 80kOe at 9K