SNP- and haplotype-based genome-wide association studies for growth, carcass, and meat quality traits in a Duroc multigenerational population

Average linkage disequilibrium coefficient (r2) values plotted against intermarker distance for all autosomal chromosomes. (PDF 407 kb

Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model

Ablファミリーチロシンキナーゼが抗体の血管外輸送を制御することを解明 --生体内での抗体輸送メカニズム--. 京都大学プレスリリース. 2019-10-21.The pathway of homeostatic IgG extravasation is not fully understood, in spite of its importance for the maintenance of host immunity, the management of autoantibody-mediated disorders, and the use of antibody-based biologics. Here we show in a murine model of pemphigus, a prototypic cutaneous autoantibody-mediated disorder, that blood-circulating IgG extravasates into the skin in a time- and dose-dependent manner under homeostatic conditions. This IgG extravasation is unaffected by depletion of Fcγ receptors, but is largely attenuated by specific ablation of dynamin-dependent endocytic vesicle formation in blood endothelial cells (BECs). Among dynamin-dependent endocytic vesicles, IgG co-localizes well with caveolae in cultured BECs. An Abl family tyrosine kinase inhibitor imatinib, which reduces caveolae-mediated endocytosis, impairs IgG extravasation in the skin and attenuates the murine pemphigus manifestations. Our study highlights the kinetics of IgG extravasation in vivo, which might be a clue to understand the pathological mechanism of autoantibody-mediated autoimmune disorders

Impact of recipient age on outcome of ABO-incompatible living-donor liver transplantation

Transplantation of hepatic grafts from ABO-incompatible donors is controversial because of the risk of hyperacute rejection mediated by preformed anti-ABO antibodies. The aim of the present study was to evaluate the outcome of liver transplants performed with ABO-incompatible living-donor livers and to detect risk factors for development of complications

Risk Management of Heatstroke Based on Fast Computation of Temperature and Water Loss using Weather Data for Exposure to Ambient Heat and Solar Radiation

Several indexes, such as the heat index, wet-bulb globe temperature, and the universal thermal climate index, are used to estimate the risk of seasonal heat illness. These indexes correspond to the heat load of an individual in identical environmental conditions for a prolonged period of time. In daily life, the environment changes with time, and different individuals are vulnerable to heat-related illness to different degrees. An appropriate health risk assessment covering 90% of the population would facilitate an effective response to increased rates of heat illness for major summer sport events and the elderly in daily life. In this study, a fast computation for simulating temperature elevation and sweating is implemented using weather forecast data. In particular, a bioheat equation considering thermoregulatory responses is solved in the time domain using anatomical human body models including young adults, the elderly, and children. To accelerate simulation, the computational code is vectorized and parallelized, and subsequently implemented on an SX-ACE supercomputer. The computational results are validated in typical cases of young adults, children, and the elderly. The computational time for estimating the body temperature elevation and water loss for three hours based on the forecasted temperature, humidity, and solar radiation was 8 min for a total of nine human models that cover an estimated 90% of the population. This demonstrates the effectiveness of the proposed system for pre-emptive health risk management. To improve public awareness, a web-based risk management application has been developed and used since the spring of 2017 in Japan.Peer reviewe

Adrenal function during long-term ACTH therapy for patients with developmental and epileptic encephalopathy

Some patients with developmental and epileptic encephalopathy (DEE) respond to adrenocorticotropic hormone (ACTH) therapy but relapse soon after. While long-term ACTH therapy (LT-ACTH) has been attempted for these patients, no previous studies have carefully assessed adrenal function during LT-ACTH. We evaluated the effectiveness of LT-ACTH, as well as adverse effects (AE), including their adrenal function in three DEE patients. Patients underwent a corticotropin-releasing hormone (CRH) stimulation test during LT-ACTH, and those with peak serum cortisol below 15 mu g/dL were considered to be at high risk of adrenal insufficiency (AI). Two of three responded, and their life-threatening seizures with postgeneralized electroencephalogram (EEG) suppression decreased. Although no individuals had serious AE, CRH stimulation test revealed relatively weak responses, without reaching normal cortisol peak level (18 mu g/dL). Hydrocortisone replacement during stress was prepared in a case with lower cortisol peak than our cutoff level. LT-ACTH could be a promising treatment option for cases of DEE that relapse soon after effective ACTH treatment. The longer duration and larger cumulative dosage in LT-ACTH than in conventional ACTH could increase the relative risk of AI. Careful evaluation with pediatric endocrinologists, including hormonal stimulation tests, might be useful for continuing this treatment safely