Effect of chronic ethanol exposure on the liver of Clock-mutant mice

In humans, chronic ethanol consumption leads to a characteristic set of changes to the metabolism of lipids in the liver that is referred to as an "alcoholic fatty liver (AFL)". In severe cases, these metabolic changes result in the enlargement and fibrillization of the liver and are considered risk factors for cirrhosis and liver cancer. Clock-mutant mice have been shown to display abnormal lipid metabolism and alcohol preferences. To further understand the potential interactions between ethanol consumption, lipid metabolism, and the circadian clock, we investigated the effect of chronic ethanol intake on the lipid metabolism of Clock-mutant mice. We found that ethanol treatment produced a number of changes in the liver of Clock-mutant mice without impacting the wild-type controls. First, we found that 8 weeks of exposure to ethanol in the drinking water increased the weight of the liver in Clock-mutant mice. Ethanol treatment also increased triglyceride content of liver in Clock-mutant and wild-type mice. This increase was larger in the mutant mice. Finally, ethanol treatment altered the expression of a number of genes related to lipid metabolism in the Clock-mutant mice. Interestingly, this treatment did not impact circadian clock gene expression in the liver of either genotype. Thus, ethanol produces a number of changes in the liver of Clock-mutant mice that are not seen in the wild-type mice. These changes are consistent with the possibility that disturbance of circadian rhythmicity associated with the Clock mutation could be a risk factor for the development of an alcoholic fatty liver

Molecular Basis on Nitrogen Utilization in Rice(Recent Topics of the Agricultunal Biological Science in Tohoku University)

Rice (Oryza sativa L.) is the major provision for half of the world population and is the important model crop in terms of synteny. Nitrogen is a massive prerequisite element for rice during its life span. During evolutionary processes, rice has acquired strategic systems of nitrogen metabolism for the survival, i.e., the highly efficient ammonium assimilation in roots and nitrogen remobilization (nitrogen recycling). In our laboratory, research is underway to elucidate molecular mechanisms, cellular functions and the communication mechanisms in nitrogen metabolisms, especially ammonium assimilation in roots and nitrogen recycling, in rice. In this article, aim and overview of our research projects, and some recent research topics are shown

Event style preferences in medical education and research meetings in Japan

Purpose: With the spread of COVID-19, medical education and research events have either been cancelled or shifted to online or hybrid mode. However, there are no accurate records containing the exact number of these events in new modes. This study explores trends in event modes of medical education and research in Japan using registered event data from a web service. Methods: We collected event data from January 2019 to December 2021. Text mining was used to extract and classify data into categories such as on-site and online events. Then, the annual and monthly numbers of categories were counted. Results: The total number of events in March 2020 was drastically reduced, but it recovered in November 2021 to a level equivalent to that of the peak month in 2019. The majority of the events were online by December 2020, increasing in number from March 2020. Hybrid events that integrate on-site and online modes later outnumbered online events and accounted for approximately 20% of the total in June, October, and November 2021. Conclusions: The online and hybrid modes ensured the continuation of medical education and research events during the pandemic. Though online events may reduce after COVID-19, the hybrid mode could become a popular mode that offers diversity

Disorder of Higher Brain Function in Myotonlc Dystrophy

筋強直性ジストロフィー(以下Mypとする)は第19番染色体長腕にあるMyD原因遺伝子のCTGリピート数の異常増大により発症する常染色体優性遺伝の疾患である。本症では高頻度に中枢神経障害を伴うことが知られており、記憶力や注意力、遂行機能能力、構成能力などの高次脳機能障害がみられる。今回、本症例7例について海馬領域が陳述記憶の中枢として重要であることから頭部MRIで海馬領域の計測を行い、その計測結果と日本語版ウェクスラー記憶検査との比較及び正常コントロール群の計測結果との比較を行った。同時に大脳萎縮についても計測、比較した。さらに知能検査、記憶検査、事象関連電位などとCTGリピート数との関連についも検討した。結論としてMyD群の海馬領域計測では記憶の様式特異性障害が示され、さらに海馬領域を含めた大脳全体の萎縮が示された。また事象関連電位P300とCTGリピートの増大との相関が新たに示された。Myotonic dystrophy (Myp) is an autosomaI dominantly inherited disease. This abnormal gepe for Myp is localized to chromosome 19ql3.3 as an expansion of CTG repeat. There is a correIation between the number of CTG repeats and the severity of clinical symptoms. MyD has been noticed accompanying CNS disorders such as disturbance of memory, attention, executive function and construction. We measured cerebral and hippocampal areas of 7 patients with MyD by MRI Hippocampus is one of important areas of declarative memory, therefore it was examined if there was a correlation between the hippocampaI areas of the patients and the scores of Wechsler Memory Scale-Revised (WMS-R). WechsIer Adult Intelligent Scale-Revised (WAIS-R) and event-related potentia1 P300 were also performed for the patients. Then we anaIyzed a correlation to the number of CTG repeats and each datum. In conclusion, an expansion of CTG repeat was correIated to onset, WMS-R andP300 in the patients. And diffuse brain atrophy was observed and correlated to WAIS-R. Also, the degree of hippocampaI atrophy was significantly correIated to the score of WMS-R, especially verbaI memory tests. It was first found that there was a significant correlation between the latency of P300 and the number of CTG repeats in MyD. These results suggest that CTG expansion and brain atrophy relate to disorder of higher brain function in MyD

Prediction Models for BMI and NAFLD

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. Disulfide bond‐forming oxidoreductase A‐like protein (DsbA‐L) is known to be a key molecule in protection against obesity and obesity‐induced inflammation. In the present study, we used a modeling and simulation approach in an attempt to develop body mass index (BMI) and BMI‐based NAFLD prediction models incorporating the DsbA‐L polymorphism to predict the BMI and NAFLD in 341 elderly subjects. A nonlinear mixed‐effect model best represented the sigmoidal relationship between the BMI and the logit function of the probability of NAFLD prevalence. The final models for BMI and NAFLD showed that DsbA‐L rs1917760 polymorphism, age, and gender were associated with the BMI, whereas gender, patatin‐like phospholipase 3 rs738409 polymorphism, HbA1c, and high‐density and low‐density lipoprotein cholesterol levels were associated with the risk of NAFLD. This information may aid in the genetic‐based prevention of obesity and NAFLD in the general elderly population

Subcellular localization of glucocorticoid receptor protein in the human kidney glomerulus

Subcellular localization of glucocorticoid receptor protein in the human kidney glomerulus.BackgroundThe detailed mechanisms of glucocorticoid action in idiopathic nephrotic syndrome and progressive glomerulonephritides have not been clearly elucidated. The pharmacological actions of glucocorticoids are mediated by their binding to an intracellular protein, the glucocorticoid receptor (GR). The determination of GR localization in normal glomerular cells is essential to elucidate the mechanisms of glucocorticoid action in various glomerular diseases.MethodsWe carried out an immunoblot examination using antihuman GR-specific antibody and homogenates of isolated normal human glomeruli and mesangial cells in culture. Immunohistochemical examinations were also performed on normal human kidney specimens at light and electron microscopic levels. The nuclear translocation of GRs elicited by ligand binding was further investigated by confocal laser-scanning microscopic inspection of freshly isolated glomeruli and mesangial cells cultured with dexamethasone.ResultsAn immunoblot examination demonstrated the presence of a 94 kDa protein, a molecular weight consistent with that of GRs, in the homogenates of glomeruli and cultured mesangial cells. By light microscopic examination, GRs were strongly detected in the nucleus and moderately in the cytoplasm of all glomerular cells, parietal and visceral epithelial cells, endothelial cells, and mesangial cells. By electron microscopic examination, the nuclear GRs of all glomerular cells were found to be diffusely distributed in the euchromatin. Additionally, the immunofluorescence intensities of nuclear GRs in isolated glomeruli and mesangial cells in culture became more intense by the addition of dexamethasone.ConclusionsOur findings suggest that all subsets of human glomerular cells definitely express the GR protein, which potentially undergoes translocation by glucocorticoids

Functional Sperm of the Yellowtail (Seriola quinqueradiata) Were Produced in the Small-Bodied Surrogate, Jack Mackerel (Trachurus japonicus).

Production of xenogeneic gametes from large-bodied, commercially important marine species in closely related smaller surrogates with short generation times may enable rapid domestication of the targeted species. In this study we aimed to produce gametes of Japanese yellowtail (Seriola quinqueradiata) using jack mackerel (Trachurus japonicus) as a surrogate with a smaller body size and shorter maturation period. Donor spermatogonia were collected from the testes of yellowtail males and transferred into the peritoneal cavity of 10- and 12-day-old jack mackerel larvae. Twenty days later, 59.5% of the recipients survived of which 88.2% had donor-derived germ cells in their gonads. One year later, genomic DNA templates were prepared from the semen of 96 male recipients and subjected to PCR analyses using primers specific for the yellowtail vasa sequence, resulting in the detection of positive signals in semen from two recipients. The milt collected from the recipients was used for fertilization with yellowtail eggs. Of eight hatchlings obtained from the crosses, two were confirmed to be derived from donor yellowtail by DNA markers, although the others were gynogenetic diploids. These findings indicate that it is possible to produce donor-derived sperm in xenogeneic recipients with smaller body size and shorter generation time by transplanting spermatogonia. Thus, the xenogeneic transplantation of spermatogonia might be a potential tool to produce gametes of large-bodied, commercially important fish although the efficiency of the method requires further improvement. This is the first report demonstrating that donor-derived sperm could be produced in xenogeneic recipient via spermatogonial transplantation in carangid fishes