Photoemission from the gas phase using soft x-ray fs pulses: An investigation of the space-charge effects

An experimental and computational investigation of the space-charge effects occurring in ultrafast photoelectron spectroscopy from the gas phase is presented. The target sample CF$_3$I is excited by ultrashort (100 fs) far-ultraviolet radiation pulses produced by a free-electron laser. The modification of the energy distribution of the photoelectrons, i.e. the shift and broadening of the spectral structures, is monitored as a function of the pulse intensity. A novel computational approach is presented in which a survey spectrum acquired at low radiation fluence is used to determine the initial energy distribution of the electrons after the photoemission event. The spectrum modified by the space-charge effects is then reproduced by $N$-body calculations that simulate the dynamics of the photoelectrons subject to the mutual Coulomb repulsion and to the attractive force of the positive ions. The employed numerical method allows to reproduce the complete photoelectron spectrum and not just a specific photoemission structure. The simulations also provide information on the time evolution of the space-charge effects on the picosecond scale. Differences with the case of photoemission from solid samples are highlighted and discussed. The presented simulation procedure constitutes an effective tool to predict and account for space-charge effect in time-resolved photoemission experiments with high-intensity pulsed sources.Comment: 18 pages, 4 figures, 1 tabl

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

Clinical factor affecting the recovery of kidney function in clinically localized renal cell carcinoma patients who underwent nephron-sparing surgery.

INTRODUCTION:Nephron-sparing surgery (NSS) has become the standard treatment for small renal cell carcinoma because of its comparable oncological outcome and superior patient survival compared to total nephrectomy. However, the precise chronological course of recovery from initial kidney damage and the factors responsible for it remain unknown. MATERIALS AND METHODS:Seventy-one patients who underwent NSS were enrolled. To elucidate the chronological changes in kidney function that occur after NSS, the estimated glomerular filtration rate (eGFR) was calculated at different two points, the early (7 days after surgery) and late time points (more than 12 months after surgery), and compared with the preoperative eGFR. Perioperative factors were applied to a multivariate regression model to investigate the factors that most affect patient recovery from nephron damage. RESULTS:eGFR was decreased at the early time point but had partially recovered at the late time point. Male gender, ischemic time, and tumor size were found to be significant predictors of the initial drop in eGFR. The only significant factor that prevented later functional recovery was the presence of DM. CONCLUSION:Several perioperative factors significantly influence early kidney damage; however, the presence of DM is the only factor affecting the risk of long-term chronic kidney damage

Regional secondary focal segmental glomerulosclerosis in a transplanted kidney : resolution with treatment of a segmental renal artery stenosis

Background: Conditions associated with high intraglomerular filtration pressure can cause secondary focal segmental glomerulosclerosis (FSGS). Unilateral renal artery stenosis (RAS) or its occlusion results in FSGS-like changes and the nephrotic syndrome in the contralateral kidney due to hyperfiltration. However, it has been rarely reported that stenosis of a renal arterial branch can result in FSGS-like changes in a different portion in the same kidney allograft. Case presentation: A 60-year-old male kidney recipient developed allograft dysfunction after angiotensin II receptor blockade for hypertension 4 months after transplantation. It was proven that one of two arterial branches of the graft was markedly stenotic. Graft dysfunction improved after percutaneous transluminal arterioplasty (PTA), however; the stenosis recurred and massive proteinuria developed 5 months later. Graft biopsy showed ischemic changes in the region fed by the stenotic artery branch and in contrast FSGS-like changes in the region fed by the other branch. His clinicopathological manifestation including massive proteinuria almost normalized after the repeat PTA. Conclusion: Here we report a case of secondary FSGS of a kidney allograft due to severe RAS of a branch of the same kidney, in which clinical and pathological improvement were confirmed after radiological intervention. When moderate to severe proteinuria appear, secondarily developed FSGS as well as primary (recurrent or de novo) FSGS should be taken into account in kidney transplant recipients

Successful Kidney Transplantation Ameliorates Arterial Stiffness in End-Stage Renal Disease Patients

Purpose: Successful kidney transplantation (KTx) can ameliorate bodily damage caused by end-stage renal disease (ESRD). Arterial stiffness (AS) is one of the critical factors, that shorten the survival of patients due to cardiovascular events. KTx may reduce AS as well; however, this has not been investigated well. We therefore conducted a retrospective study using non-invasive pulse wave velocity (PWV), which is a useful index of aortic damage. Patients and methods: Fifty-eight consecutive kidney recipients (34 men, 24 women) were enrolled in this study. Mean age at transplantation was 40.5±12.3 years and the dialysis period was 73.1±95.8 months. The brachial-ankle PWV was measured preoperatively and six months postoperatively. First, we investigated the relationship between the PWV and the other parameters related to AS. Second, we studied the pre- to post-transplant change in PWV to evaluate the amelioration of AS after successful kidney transplantation. Results: PWV showed significant positive correlations with age, systolic blood pressure (BP), diastolic BP and abdominal aortic calcification index. After successful KTx, PWV significantly decreased. (P < 0.01) In addition, systolic and diastolic BP significantly decreased. (P < 0.01 and P < 0.05, respectively) Conclusion: Successful KTx ameliorates AS in ESRD patients. This might explain the improved cardiovascular prognosis of ESRD patients who undergo kidney transplantation