Tropical Rainfall Measurement Mission (TRMM) Operation Summary

The Tropical Rainfall Measurement Mission (TRMM) is a joint U.S. and Japan mission to observe tropical rainfall, which was launched by H-II No. 6 from Tanegashima in Japan at 6:27 JST on November 28, 1997. After the two-month commissioning of TRMM satellite and instruments, the original nominal mission lifetime was three years. In fact, the operations has continued for approximately 17.5 years. This paper provides a summary of the long term operations of TRMM

Intraspecies Prion Transmission Results in Selection of Sheep Scrapie Strains

Background: Sheep scrapie is caused by multiple prion strains, which have been classified on the basis of their biological characteristics in inbred mice. The heterogeneity of natural scrapie prions in individual sheep and in sheep flocks has not been clearly defined. Methodology/Principal Findings: In this study, we intravenously injected 2 sheep (Suffolk and Corriedale) with material from a natural case of sheep scrapie (Suffolk breed). These 3 sheep had identical prion protein (PrP) genotypes. The protease-resistant core of PrP (PrPres) in the experimental Suffolk sheep was similar to that in the original Suffolk sheep. In contrast, PrPres in the Corriedale sheep differed from the original PrPres but resembled the unusual scrapie isolate, CH1641. This unusual PrPres was not detected in the original sheep. The PrPres distributions in the brain and peripheral tissues differed between the 2 breeds of challenged sheep. A transmission study in wild-type and TgBoPrP mice, which overexpressing bovine PrP, led to the selection of different prion strains. The pathological features of prion diseases are thought to depend on the dominantly propagated strain. Conclusions/Significance: Our results indicate that prion strain selection occurs after both inter- and intraspecie

Sulfated Dextrans Enhance In Vitro Amplification of Bovine Spongiform Encephalopathy PrPSc and Enable Ultrasensitive Detection of Bovine PrPSc

Prions, infectious agents associated with prion diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep and goats, are primarily comprised of PrP(Sc), a protease-resistant misfolded isoform of the cellular prion protein PrP(C). Protein misfolding cyclic amplification (PMCA) is a highly sensitive technique used to detect minute amounts of scrapie PrP(Sc). However, the current PMCA technique has been unsuccessful in achieving good amplification in cattle. The detailed distribution of PrP(Sc) in BSE-affected cattle therefore remains unknown.We report here that PrP(Sc) derived from BSE-affected cattle can be amplified ultra-efficiently by PMCA in the presence of sulfated dextran compounds. This method is capable of amplifying very small amounts of PrP(Sc) from the saliva, palatine tonsils, lymph nodes, ileocecal region, and muscular tissues of BSE-affected cattle. Individual differences in the distribution of PrP(Sc) in spleen and cerebrospinal fluid samples were observed in terminal-stage animals. However, the presence of PrP(Sc) in blood was not substantiated in the BSE-affected cattle examined.The distribution of PrP(Sc) is not restricted to the nervous system and can spread to peripheral tissues in the terminal disease stage. The finding that PrP(Sc) could be amplified in the saliva of an asymptomatic animal suggests a potential usefulness of this technique for BSE diagnosis. This highly sensitive method also has other practical applications, including safety evaluation or safety assurance of products and byproducts manufactured from bovine source materials

Accumulation of L-type Bovine Prions in Peripheral Nerve Tissues

We recently reported the intraspecies transmission of L-type atypical bovine spongiform encephalopathy (BSE). To clarify the peripheral pathogenesis of L-type BSE, we studied prion distribution in nerve and lymphoid tissues obtained from experimentally challenged cattle. As with classical BSE prions, L-type BSE prions accumulated in central and peripheral nerve tissues

Anti-Prion Activity of Brilliant Blue G

BACKGROUND: Prion diseases are fatal neurodegenerative disorders with no effective therapy currently available. Accumulating evidence has implicated over-activation of P2X7 ionotropic purinergic receptor (P2X7R) in the progression of neuronal loss in several neurodegenerative diseases. This has led to the speculation that simultaneous blockade of this receptor and prion replication can be an effective therapeutic strategy for prion diseases. We have focused on Brilliant Blue G (BBG), a well-known P2X7R antagonist, possessing a chemical structure expected to confer anti-prion activity and examined its inhibitory effect on the accumulation of pathogenic isoforms of prion protein (PrPres) in a cellular and a mouse model of prion disease in order to determine its therapeutic potential. PRINCIPAL FINDINGS: BBG prevented PrPres accumulation in infected MG20 microglial and N2a neural cells at 50% inhibitory concentrations of 14.6 and 3.2 µM, respectively. Administration of BBG in vivo also reduced PrPres accumulation in the brains of mice with prion disease. However, it did not appear to alleviate the disease progression compared to the vehicle-treated controls, implying a complex role of P2X7R on the neuronal degeneration in prion diseases. SIGNIFICANCE: These results provide novel insights into the pathophysiology of prion diseases and have important implications for the treatment

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

A new model of development of the mammalian ovary and follicles

Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells penetrate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 80) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 26 markers for GREL and other cells and extracellular matrix we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the gonadal ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are always separated from the stroma by a basal lamina. Around 130 days of gestation the stroma expands laterally below the outermost layers of GREL cells forming a sub-epithelial basal lamina and establishing an epithelial-stromal interface. It is at this stage that a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells, all enclosed by a basal lamina. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not penetrate into the ovary to form the granulosa cells of follicles, instead ovarian surface epithelial cells and granulosa cells have a common precursor, the GREL cell.Katja Hummitzsch, Helen F. Irving-Rodgers, Nicholas Hatzirodos, Wendy Bonner, Laetitia Sabatier, Dieter P. Reinhardt, Yoshikazu Sado, Yoshifumi Ninomiya, Dagmar Wilhelm and Raymond J. Rodger

Spatial Influence of Multifaceted Environmental States on Habitat Quality: A Case Study of the Three Largest Chinese Urban Agglomerations

Habitat structure and quality in the urban agglomeration (UA) are subject to multiple threats and pressures due to ongoing anthropogenic activities and call for comprehensively effective solutions. Many approaches, including cartographic comparison, correlation analysis, the local entropy model, and GeoDetector, were jointly used to clarify the interplay between habitat quality and multiple environmental issues. In response to the overlapped risks of diverse environmental systems, this study presented an integrated research framework to evaluate the spatial influences of multifaceted environmental situations on habitat quality. We conducted the case study in the three largest Chinese UAs: Beijing–Tianjin–Hebei (BTH), Greater Bay Area (GBA), and Yangtze River Delta (YRD). The evaluation results show that the three UAs shared similarities and differences in relationship/impact types and their strengths. In 2015, most of the three UAs’ landscapes delivered low–medium magnitudes of habitat quality (score <0.7) and emerged with unevenly severe consequences over space across different environmental aspects, highlighting the importance of maintaining habitat safety. Overall, habitat quality scores were synergistic with NDVI, but antagonistic to surface heat island intensity (SHII), PM2.5 concentrations, and residential support. However, locally structured relationships exhibited geographical complexity and heterogeneity between habitat quality and environmental systems. Regarding GeoDetector evaluation, PM2.5 concentrations in BTH, SHII in GBA, and NDVI in YRD played a dominant role in single-factor and interaction analysis. More importantly, the synergistic effect of various environmental issues on habitats was manifested as mutually enhanced rather than independent or weakened interactive effects, implying the aggravation of compound effects and the necessity of prioritization schemes. This study could provide beneficial insights into the interconnections between habitats’ sustainability and multifaceted environmental situations in UAs

Qualitative research on the mechanism of choking under pressure

The objective of this study was to propose an inductive model for the process of choking under pressure by qualitatively investigating factors related to choking and their relationships. Thirteen athletes (M=7, F=6) on the varsity in soft tennis, football, basketball, badminton, and archery teams participated in a semi-structured interview in which questions concerning the conditions, symptoms, causes, coping strategies, and social support for choking were asked for approximately one hour. The verbal protocols from the interview were analyzed by a Grounded-Theory Approach (GTA). The results of the GTA produced a model consisting of the following 13 categories: (1) stressor, (2) pre-competition condition, (3) individual characteristics, (4) irrational belief, (5) negative affect, (6) safe strategy, (7) verbal and behavioral changes, (8) activation of physiological arousal level, (9) physical fatigue, (10) changes in perception and motor control, (11) performance decrements, (12) coping strategy, and (13) vicious circle. This model emphasizes the categories of safe strategy, changes in perception and motor control, and physical fatigue, which are directly related to decrements in performance. In addition, the model points out the importance of the vicious circle of choking. Hypotheses proposed to explain the choking phenomenon in previous studies, such as those involving conscious control and processing resource shortages, focused on attentional changes. It is, however, necessary to consider other factors as well, such as the strategy, perceptual and movement characteristics, physical fatigue, and circulatory process in order to understand the mechanism of choking