Assembly of the Inner Perivitelline Layer, a Homo log of the Mammalian Zona Pellucida: An Immunohistochemical and Ultrastructural Study

The avian inner perivitelline layer (IPVL), a homologous structure to the mammalian zona pellucida, is deposited between the granulosa cells and the oocyte cell membrane during folliculogenesis. The glycoprotein meshwork of the IPVL forms a 3-dimensional matrix and possesses important functions in the fertilization process: it contributes to the binding of avian spermatozoa to the oocyte and induces acrosomal exocytosis. In contrast to the zona pellucida of mammals, the IPVL does not prevent the physiological polyspermy found in birds. Previous studies have shown that in the Japanese quail (Cotumix japonica) at least 5 glycoproteins are constituents of the IPVL (ZP1, ZP2, ZP3, ZP4, and ZPD). In this study, we investigated the spatiotennporal assembly pattern of the IPVL during folliculogenesis using immunohistochemical and ultrastructural methods. The obtained results clearly show that these glycoproteins are incorporated into the IPVL at distinct points during follicular development, supporting the hypothesis that ZP2 and ZP4 form a type of prematrix into which ZP1, ZP3, and ZPD are integrated at a later stage of development. Copyright (C) 2011 S. Karger AG, Base

Have we already detected astrophysical symptoms of space-time noncommutativity ?

We discuss astrophysical implications of $\kappa$-Minkowski space-time, in which there appears space-time noncommutativity. We first derive a velocity formula for particles based on the motion of a wave packet. The result is that a massless particle moves at a constant speed as in the usual Minkowski space-time, which implies that an arrival time analysis by $\gamma$-rays from Markarian (Mk) 421 does not exclude space-time noncommutativity. Based on this observation, we analyze reaction processes in $\kappa$-Minkowski space-time which are related to the puzzling detections of extremely high-energy cosmic rays above the Greisen-Zatsepin-Kuzmin cutoff and of high-energy ($\sim$20 TeV) $\gamma$-rays from Mk 501.Comment: 10 pages, 6 figures, submitted to PRD, corrected some mistake

Validation of the vertical profiles of HCl over the wide range of the stratosphere to the lower thermosphere measured by SMILES

Hydrogen chloride (HCl) is the most abundant (more than 95 %) among inorganic chlorine compounds Cly in the stratosphere. The HCl molecule has been observed to obtain long-term quantitative estimations of total budget of the stratospheric anthropogenic chlorine compounds. In this study, we provided HCl vertical profiles at altitudes of 16–100 km using the superconducting submillimeter-wave limb-emission sounder (SMILES) from space. We used the SMILES Level-2 research product version 3.0.0. The period of the SMILES HCl observation was from October 12, 2009 to April 21, 2010, and the latitude coverage was 40S–65N. The average HCl vertical profile showed an increase with altitude up to the stratopause (~ 45 km), approximately constant values between the stratopause and the upper mesosphere (~ 80 km), and a decrease from the mesopause to the lower thermosphere (~ 100 km). This behavior was observed in the all latitude regions, and reproduced by the SD-WACCM model. We compared the SMILES HCl vertical profiles in the stratosphere and lower mesosphere with HCl profiles from MLS on the Aura satellite, as well as from ACE-FTS on SCISAT and from TELIS (balloon-borne). The TELIS observations were performed using the superconductive limb emission technique, as used by SMILES. The globally averaged vertical HCl profiles of SMILES well agreed with those of MLS and ACE-FTS within 0.25 and 0.2 ppbv between 20 and 40 km, respectively. The SMILES HCl concentration was smaller than those of MLS and ACE/FTS as the altitude increased from 40 km, and the difference was approximately 0.4–0.5 ppbv at 50–60 km. The difference between SMILES and TELIS HCl observations was about 0.3 ppbv in the polar winter region between 20 and 34 km, except near 26 km. SMILES HCl error sources that may cause discrepancies with the other observations are investigated by a theoretical error analysis. We calculated errors caused by the uncertainties of spectroscopic parameters, instrument functions, and atmospheric temperature profiles. The jacobian for the temperature explains the negative bias of the SMILES HCl concentration at 50–60 km. The HCl vertical profile from the middle troposphere to the lower thermosphere is reported for the first time from SMILES observations; the data quality is quantified by comparisons with other measurements and via theoretical error analysis

Work-related allergy in medical doctors: atopy, exposure to domestic animals, eczema induced by common chemicals and membership of the surgical profession as potential risk factors

Purpose To investigate the risk factors associated with work-related allergy-like symptoms in medical doctors. Methods Self-administered questionnaire survey and CAP test were conducted among medical school students in the 4th grade of their 6-year medical course in 1993–1996 and 1999–2001. Follow-up questionnaires were sent in 2004 to the graduates. These questionnaires enquired into personal and family history of allergic diseases, lifestyle, history of allergy-like symptoms including work-relatedness and occupational history as medical doctors. Relationships between allergy-like symptoms and relevant factors were evaluated by multivariate logistic regression analysis. Results Of 261 respondents at the follow-up survey, 139 (53.3%) and 54 (20.7%) had a history of any allergy-like symptoms and any work-related allergy-like symptoms, respectively. Female gender and family history of allergic diseases were signiWcantly associated with any allergy-like symptoms. Personal history of allergic disease, exposure to domestic animals, eczema caused by rubber gloves, metallic accessories, or cosmetics during schooling days, and membership of the surgical profession were signiW- cant risk factors for work-related allergy-like symptoms. On the contrary, to work-related allergy-like symptoms, gender, age, and smoking status were not signiWcantly related, and consumption of prepared foods was inversely related. Conclusions Personal history of atopy and eczema induced by common goods and the history of keeping domestic animals may be predictors of work-related allergy-like symptoms in doctors. After graduation from medical school, physicians start with exposure to various allergens and irritants at work, which relate to work-related allergy-like symptoms, especially for surgeons

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

Lancet

BACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). INTERPRETATION: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. FUNDING: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation