Molecular Pathology of Murine Ureteritis Causing Obstructive Uropathy with Hydronephrosis

Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents

Multidimensional background examination of young underweight Japanese women: focusing on their dieting experiences

IntroductionThis study examines the background of underweight young women in Japan from multiple perspectives, focusing on whether they have ever dieted.MethodsA screening survey was administered to 5,905 underweight (BMI < 18.5 kg/m2) women aged 18–29 years, who could report their birth weight recorded in their mother-child handbook. Valid responses were obtained from 400 underweight and 189 normal-weight women. The survey collected data regarding height, weight (BMI), body image and perception of weight, dieting experience, exercise habits from elementary school age onwards, and current eating habits. Additionally, five standardized questionnaires were used (EAT-26, eHEALTH, SATAQ-3 JS, TIPI-J, and RSES). The primary analysis was a comparative analysis (t-test/χ2)—with the presence or absence of underweight and diet experience as independent variables, and each questionnaire as a dependent variable.ResultsThe screening survey revealed that approximately 24% of the total population was underweight, with a low mean BMI. Of the respondents, more than half reported their body image as skinny and a small percentage as obese. Compared with the non-diet-experienced group (NDG), the diet-experienced group (DG) had a significantly higher proportion of past to current exercise habits. There was a significantly higher percentage of disagreement responses from the DG for weight and food gain than for the NDG. The NDG weighed significantly less than the DG in terms of birth weight, and lost weight easier than the DG. Additionally, the NDG was significantly more likely to agree with increasing weight and food intake. The NDG’s exercise habits were below 40% from elementary school age to the present, predominantly owing to a dislike for exercise and a lack of opportunity to implement it. In the standardized questionnaire, the DG was significantly higher for EAT-26, eHEALTH, SATAQ-3 JS, and Conscientiousness (TIPI-J), whereas the NDG was only significantly higher for Openness (TIPI-J).DiscussionThe results suggest the need for different health education programs for underweight women who desire to lose weight and experience dieting and for those who do not. This study’s results are reflected in the development of sports opportunities optimized for each individual, and in the development of measures to ensure adequate nutritional intake

Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice

We previously demonstrated that female Runx3 knockout (Runx3-/-) mice were anovulatory and their uteri were atrophic and that Runx3 mRNA was expressed in granulosa cells. To clarify how Runx3 regulates folliculogenesis and ovulation, we examine the effects of Runx3 knockout on the gene expression of growth factors associated with folliculogenesis and enzymes associated with steroidogenesis. In Runx3-/- mouse ovaries, the numbers of primary and antral follicles were lower than those in wild-type (wt) mice at 3 weeks of age, indicating that the loss of Runx3 affects folliculogenesis. The expression of genes encoding activin and inhibin subunits (Inha, Inhba and Inhbb) was also decreased in ovaries from the Runx3-/- mice compared with that in wt mice. Moreover, the expression of the genes Cyp11a1 and Cyp19a1 encoding steroidogenic enzymes was also decreased. In cultured granulosa cells from 3-week-old mouse ovaries, Cyp19a1 mRNA levels were lower in Runx3-/- mice than those in wt mice. Follicle-stimulating hormone (FSH) treatment increased Cyp19a1 mRNA levels in both wt and Runx3-/- granulosa cells in culture but the mRNA level in Runx3-/- granulosa cells was lower than that in wt ones, indicating that granulosa cells could not fully function in the absence of Runx3. At 3 weeks of age, gonadotropin α subunit, FSHβ subunit and luteinizing hormone (LH) β subunit mRNA levels were decreased in Runx3-/- mice. These findings suggest that Runx3 plays a key role in female reproduction by regulating folliculogenesis and steroidogenesis in granulosa cells

Identification of Small-Molecule Inhibitors of Neutral Ceramidase (nCDase) via Target-Based High-Throughput Screening

There is interest in developing inhibitors of human neutral ceramidase (nCDase) because this enzyme plays a critical role in colon cancer. There are currently no potent or clinically effective inhibitors for nCDase reported to date, so we adapted a fluorescence-based enzyme activity method to a high-throughput screening format. We opted to use an assay whereby nCDase hydrolyzes the substrate RBM 14-16, and the addition of NaIO4 acts as an oxidant that releases umbelliferone, resulting in a fluorescent signal. As designed, test compounds that act as ceramidase inhibitors will prevent the hydrolysis of RBM 14-16, thereby decreasing fluorescence. This assay uses a 1536-well plate format with excitation in the blue spectrum of light energy, which could be a liability, so we incorporated a counterscreen that allows for rapid selection against fluorescence artifacts to minimize false-positive hits. The high-throughput screen of >650,000 small molecules found several lead series of hits. Multiple rounds of chemical optimization ensued with improved potency in terms of IC50 and selectivity over counterscreen assays. This study describes the first large-scale high-throughput optical screening assay for nCDase inhibitors that has resulted in leads that are now being pursued in crystal docking studies and in vitro drug metabolism and pharmacokinetics (DMPK).National Cancer Institute https://doi.org/10.13039/100000054Stony Brook Cancer CenterPeer Reviewe

Discourse analytical approach for Sentence final ellipsis in an advanced Japanese language classroom

本研究は、非日本語母語話者に対する日本語のインタラクション指導の中での、中途終了型発話に焦点をあてる。日本語母語話者の自然会話では、中途終了型発話は頻繁に現れる。したがって、中途終了型発話を使えることや、中途終了型の発話を理解しながらインタラクションできることは、日本語のプロフィシエンシーの指標となりうると考えられる。本研究では、インドにある大学の日本語学科に協力を得て、１コマの授業を録画し、どのような種類の中途終了型発話が使われているか、また、話し手の中途終了型発話に対して、ほかの会話参与者はどのように対応するかを分析した。その結果、中途終了発話は見られるものの、対応の仕方が日本語母語話者とは異なっていて、習得の難しさが示唆された。The purpose of this paper is to analyze sentence final ellipsis used in a JFL (Japanese as a foreign langue) class in a university in India. Sentence final ellipsis has been said to be difficult for Japanese language learners. The participants in this research are an Indian teacher and students in the university. They talked in Japanese mainly in the class. Their talk in the class was video-taped for the analysis. It was observed that both the teacher and the students used sentence final ellipsis. However, the discourse analysis by BTSJ revealed that their way or using it and response to the sentence final ellipsis are different from the way Japanese native speakers do. The paper also discusses teaching sentence final ellipsis in JFL class.departmental bulletin pape

Psychosocial factors at work and inflammatory markers: protocol for a systematic review and meta-analysis

Introduction Chronic inflammation may be a mediator for the development of cardiovascular disease (CVD), metabolic diseases and psychotic and neurodegenerative disorders. Meta-analytic associations between work-related psychosocial factors and inflammatory markers have shown that work-related psychosocial factors could affect the flexibility and balance of the immune system. However, few systematic reviews or meta-analyses have investigated the association between work-related psychosocial factors and inflammatory markers. Based on prospective studies, the present investigation will conduct a comprehensive systematic review and meta-analysis of the association between work-related psychosocial factors and inflammatory markers.Methods and analysis The systematic review and meta-analysis will include published studies identified from electronic databases (PubMed, EMBASE, PsycINFO, PsycARTICLES, Web of Science and Japan Medical Abstracts Society) according to recommendations of the Meta-analysis of Observational Studies in Epidemiology guideline. Inclusion criteria are studies that: examined associations between work-related psychosocial factors and increased inflammatory markers; used longitudinal or prospective cohort designs; were conducted among workers; provided sufficient data for calculating ORs or relative risk with 95% CIs; were published as original articles in English or Japanese; and were published up to the end of 2017. Study selection, data extraction, quality assessment and statistical syntheses will be conducted by 14 investigators. Any inconsistencies or disagreements will be resolved through discussion. The quality of studies will be evaluated using the Risk of Bias Assessment Tool for Non-randomized Studies.Ethics and dissemination The investigation study will be based on published studies, so ethics approval is not required. The results of this study will be submitted for publication in a scientific peer-reviewed journal. The findings may be useful for assessing risk factors for increased inflammatory markers in the workplace and determining future approaches for preventing CVD, metabolic diseases and psychotic and neurodegenerative disorders

ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline

H3K9 trimethylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that in male meiosis, ATF7IP2 amasses on autosomal and X-pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X-pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase I. Analyses of ATF7IP2-deficient meiosis reveal the protein's essential roles in the maintenance of MSCI, suppression of retrotransposons, and global up-regulation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition

Transmission of Bordetella holmesii during Pertussis Outbreak, Japan

We describe the epidemiology of a pertussis outbreak in Japan in 2010–2011 and Bordetella holmesii transmission. Six patients were infected; 4 patients were students and a teacher at the same junior high school. Epidemiologic links were found between 5 patients. B. holmesii may have been transmitted from person to person

Analysis of T-cell alloantigen response via a direct pathway in kidney transplant recipients with donor-specific antibodies

Donor-specific antibodies (DSAs) are the main cause of graft loss over time. The direct pathway of alloantigen recognition is important in the pathogenesis of acute rejection. Recent studies have suggested that the direct pathway also contributes to the pathogenesis of chronic injury. Nevertheless, there are no reports on T-cell alloantigen response via the direct pathway in kidney recipients with DSAs. We analyzed the T-cell alloantigen response via the direct pathway in kidney recipients with DSAs (DSA+) or without DSAs (DSA−). A mixed lymphocyte reaction assay was implemented to assess the direct pathway response. DSA+ patients showed significantly higher CD8+ and CD4+ T cell responses to donor cells than DSA− patients. Furthermore, proliferating CD4+ T cells showed a marked increase in Th1 and Th17 responses in DSA+ patients than in DSA− patients. In a comparison between anti-donor and third-party responses, the anti-donor CD8+ and CD4+ T cell response was significantly lower than the anti-third-party response. In contrast, the donor-specific hyporesponsiveness was absent in DSA+ patients. Our study demonstrated that DSA+ recipients have a greater potential for developing immune responses against the donor tissues via the direct alloantigen recognition pathway. These data contribute to an understanding of DSAs pathogenicity during kidney transplantation