Nephrin is an important component of the barrier system in the testis.

Nephrin, a gene product of the congenital nephrotic syndrome of the Finnish type (NPHS1), is a 1242-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules. The expression of this gene is localized in rat and human glomerular epithelial cells. Here we report the expression of nephrin in various tissues other than the kidneys in mice. The expression of nephrin mRNA in various tissues of mice, including the kidneys, testes, spleen, thymus and brain, were first investigated by the RT-PCR method, and it was shown that a high level of nephrin mRNA could be detected in the testes of mice 1-6 weeks old. In situ hybridization revealed the expression of the nephrin gene in the Sertoli cells. Additionally, immunofluorescent staining studies indicated that nephrin was colocalized with anchoring protein ZO-1 in the mouse testis. From these results, it is inferred that nephrin is an important component of the barrier system in testes.</p

Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004

We analyze the data of TAMA300 detector to search for gravitational waves from inspiraling compact star binaries with masses of the component stars in the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the years 2000-2004, are used for the event search. We combine the results of different observation runs, and obtained a single upper limit on the rate of the coalescence of compact binaries in our Galaxy of 20 per year at a 90% confidence level. In this upper limit, the effect of various systematic errors such like the uncertainty of the background estimation and the calibration of the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was correcte

Observation results by the TAMA300 detector on gravitational wave bursts from stellar-core collapses

We present data-analysis schemes and results of observations with the TAMA300 gravitational-wave detector, targeting burst signals from stellar-core collapse events. In analyses for burst gravitational waves, the detection and fake-reduction schemes are different from well-investigated ones for a chirp-wave analysis, because precise waveform templates are not available. We used an excess-power filter for the extraction of gravitational-wave candidates, and developed two methods for the reduction of fake events caused by non-stationary noises of the detector. These analysis schemes were applied to real data from the TAMA300 interferometric gravitational wave detector. As a result, fake events were reduced by a factor of about 1000 in the best cases. The resultant event candidates were interpreted from an astronomical viewpoint. We set an upper limit of 2.2x10^3 events/sec on the burst gravitational-wave event rate in our Galaxy with a confidence level of 90%. This work sets a milestone and prospects on the search for burst gravitational waves, by establishing an analysis scheme for the observation data from an interferometric gravitational wave detector

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

Expression of parathyroid-related peptide mRNA in the kidney

PTHrP mRNA was quantified by RT-PCR and the localization of PTHrP mRNA was determined by in situ hybridization in kidney. During development, the expression of PTHrP mRNA is much higher before 2 weeks of age while kidney is developing. In E16 fetal mice, PTHrP mRNA was strongly expressed in the collecting ducts, urothelium of the pelvis, tubles, the glomeruli and immature elements in the cortex of the developing kidney (nephrogenic zone). within 0-day-old-mice, it was dominantly expressed in collecting ducts, the urothelium of the pelvis and nephrogenic zone. These findings suggest that PTHrP plays a role in kidney development as an autocrine/ paracrine factor

Prenatal Sociodemographic Factors Predicting Maltreatment of Children up to 3 Years Old: A Prospective Cohort Study Using Administrative Data in Japan

Identifying risk factors from pregnancy is essential for preventing child maltreatment. However, few studies have explored prenatal risk factors assessed at pregnancy registration. This study aimed to identify prenatal risk factors for child maltreatment during the first three years of life using population-level survey data from pregnancy notification forms. This prospective cohort study targeted all mothers and their infants enrolled for a 3- to 4-month-old health check between October 2013 and February 2014 in five municipalities in Aichi Prefecture, Japan, and followed them until the child turned 3 years old. Administrative records of registration with Regional Councils for Children Requiring Care (RCCRC), which is suggestive of child maltreatment cases, were linked with survey data from pregnancy notification forms registered at municipalities (n = 893). Exact logistic regression was used for analysis. A total of 11 children (1.2%) were registered with RCCRC by 3 years of age. Unmarried marital status, history of artificial abortion, and smoking during pregnancy were significantly associated with child maltreatment. Prenatal risk scores calculated as the sum of these prenatal risk factors, ranging from 0 to 7, showed high predictive power (area under receiver operating characteristic curve 0.805; 95% confidence interval (CI), 0.660–0.950) at a cut-off score of 2 (sensitivity = 72.7%, specificity = 83.2%). These findings suggest that variables from pregnancy notification forms may be predictors of the risk for child maltreatment by the age of three

Urinary Protein-to-creatinine Ratios Predict Recurrence in Pediatric and Young Adult Cases of Minimal Change Nephrotic Syndrome

High-dose steroids are required for the treatment of minimal change nephrotic syndrome (MCNS), especially for episodes of recurrence. Predicting and avoiding recurrence can help reduce the steroid dose, but prediction is currently difficult. We herein examined whether changes in laboratory data, especially the urinary protein- to-creatinine ratio (UTP/UCr), can predict clinical recurrence. We also assessed differences in clinical features between children and young adults. We included 36 patients with MCNS; for each case, we retrospectively studied laboratory data during stable remission and pre-recurrence, with the “stable” period defined as all but the 6 weeks before recurrence, and pre-recurrence defined as the 4±2 weeks before recurrence. UTP/UCr, serum albumin, etc. were measured every 5 years during stable periods. We divided patients into cohorts by age at recurrence, < 15 years and ≥ 15 years, and compared stable and pre-recurrence values for the two groups. UTP/UCr values during stable periods tended to be higher in younger patients. UTP/UCr and serum albumin showed statistically significant changes during pre-recurrence periods, but only in those aged ≥ 15 years. Thus, clinical features of recurrence differed depending on age. Signs of recurrence can be confirmed via UTP/UCr or serum albumin several weeks before recurrence in patients ≥ 15 years