Biogenesis of sperm acrosome is regulated by pre-mRNA alternative splicing of Acrbp in the mouse.

Proper biogenesis of a sperm-specific organelle, the acrosome, is essential for gamete interaction. An acrosomal matrix protein, ACRBP, is known as a proacrosin-binding protein. In mice, two forms of ACRBP, wild-type ACRBP-W and variant ACRBP-V5, are generated by pre-mRNA alternative splicing of Acrbp Here, we demonstrate the functional roles of these two ACRBP proteins. ACRBP-null male mice lacking both proteins showed a severely reduced fertility, because of malformation of the acrosome. Notably, ACRBP-null spermatids failed to form a large acrosomal granule, leading to the fragmented structure of the acrosome. The acrosome malformation was rescued by transgenic expression of ACRBP-V5 in ACRBP-null spermatids. Moreover, exogenously expressed ACRBP-W blocked autoactivation of proacrosin in the acrosome. Thus, ACRBP-V5 functions in the formation and configuration of the acrosomal granule during early spermiogenesis. The major function of ACRBP-W is to retain the inactive status of proacrosin in the acrosome until acrosomal exocytosis.

Development and Validation of a Scoring System (SAGA Score) to Predict Weight Loss in Community-Dwelling, Self-Supported Older Adults.

This retrospective cohort study explored the prevalence of substantial weight loss (≥10% per year) in independent older individuals in order to develop and validate a scoring system for high-risk group identification and targeted intervention against malnutrition. We used insurance claims and the Kokuho Database (KDB), a nationwide repository of Japanese-specific health checkups and health assessments for the older people. The study included 12,882 community-dwelling individuals aged 75 years and older who were self-supported in their activities of daily living in Saga Prefecture, Japan. Health evaluations and questionnaires categorized weight-loss factors into organic, physiological, psychological, and non-medical domains. The resulting scoring system (SAGA score), incorporating logistic regression models, predicted ≥ 10% annual weight-loss risk. The results revealed a 1.7% rate of annual substantial weight loss, with the SAGA score effectively stratifying the participants into low-, intermediate-, and high-risk categories. The high-risk category exhibited a weight-loss rate of 17.6%, highlighting the utility of this scoring system for targeted prevention. In conclusion, the validated SAGA score is a crucial tool for identifying individuals at high risk of significant weight loss, enabling tailored interventions and social support benefiting both older individuals and their relatives.

Change over Time in the Risk of Death among Japanese COVID-19 Cases Caused by the Omicron Variant Depending on Prevalence of Sublineages.

To assess temporal changes to the risk of death in COVID-19 cases caused by the Omicron variant, we calculated age-standardized case fatality rates (CFR) in patients aged ≥40 years over nine diagnostic periods (3 January to 28 August 2022) in ten Japanese prefectures (14.8 million residents). Among 552,581 study subjects, we found that there were 1836 fatalities during the isolation period (up to 28 days from date of onset). The highest age-standardized CFR (0.85%, 95% confidence interval (CI):0.78-0.92) was observed in cases diagnosed in the second 4-week period (January 31 to February 27), after which it declined significantly up to the 6th 4-week period (0.23%, 95% CI: 0.13-0.33, May 23 to June 19). The CFR then increased again but remained at 0.39% in the eighth period (July 18 to August 28). The CFR in cases with the BA.2 or BA.5 sublineages in the age range 60-80 years was significantly lower than that with BA.1 infections (60 years: 0.19%, 0.02%, 0.053%, respectively; 70 years: 0.91%, 0.33%, 0.39%; ≥80 years: 3.78%, 1.96%, 1.81%, respectively). We conclude that the risk of death in Japanese COVID-19 patients infected with Omicron variants declined through February to mid-June 2022.

Lactic acid as a major contributor to hand surface infection barrier and its association with morbidity to infectious disease.

Although the surface of the human hands contains high antimicrobial activity, studies investigating the precise components involved and the relationship between natural antimicrobial activity and morbidity in infectious diseases are limited. In this study, we developed a method to quantitatively measure the antimicrobial activity of hand surface components. Using a clinical survey, we validated the feasibility of our method and identified antimicrobial factors on the surface of the human hand. In a retrospective observational study, we compared the medical histories of the participants to assess infectious diseases. We found that the antimicrobial activity on the surface of the hands was significantly lower in the high morbidity group (N = 55) than in the low morbidity group (N = 54), indicating a positive association with the history of infection in individuals. A comprehensive analysis of the hand surface components indicated that organic acids, especially lactic acid and antimicrobial peptides, are highly correlated with antimicrobial activity. Moreover, the application of lactic acid using the amount present on the surface of the hand significantly improved the antimicrobial activity. These findings suggest that hand hygiene must be improved to enhance natural antimicrobial activity on the surface of the hands.

Mice lacking two sperm serine proteases, ACR and PRSS21, are subfertile, but the mutant sperm are infertile in vitro.

Although sperm serine protease and proteasome have long been believed to play an important role in the fertilization process, the molecular mechanism is still controversial. In this study, we have produced double-knockout mice lacking two sperm serine proteases, ACR and PRSS21, to uncover the functional role of the trypsinlike activity in fertilization. The double-knockout male mice were subfertile, likely owing to the incompleteness of fertilization in the oviductal ampulla. Despite male subfertility, the mutant epididymal sperm exhibited the inability to undergo acrosomal exocytosis on the zona pellucida (ZP) surface and to traverse the ZP, thus resulting in the failure of fertilization in vitro. The double-knockout epididymal sperm were also defective in penetration through the cumulus matrix to reach the ZP. When epididymal sperm were artificially injected into the uterus of wild-type mice, the 2-cell embryos, which had previously been fertilized by double-knockout sperm, were recovered at a low but significant level. The mutant epididymal sperm were also capable of fertilizing the oocytes in the presence of uterine fluids in vitro. These data demonstrate that the trypsinlike protease activity of ACR and PRSS21 is essential for the process of sperm penetration through the cumulus matrix and ZP in vitro, and suggest that the female reproductive tract partially compensates for the loss of the sperm function. We therefore conclude that the sperm trypsinlike activity is still important but not essential for fertilization in vivo in the mouse.

Effect of α-linolenic acid-rich diacylglycerol oil on protein kinase C activation in the rat digestive tract and lingual mucosa.

1,2-Diacylglycerol with short chain fatty acids is an endogenous activator of protein kinase C (PKC), which involved in multiple cellular processes implicated in cancer. The aim of the present study was to assess the effects of dietary α-linolenic acid-rich diacylglycerol (ALA-DAG) oil on PKC activation in the rat digestive tract and lingual mucosa in comparison with the effects of α-linolenic acid-rich triacylglycerol (ALA-TAG) oil, and common dietary oil. Membranous PKC activity in the lingual mucosa of male Wistar rats was significantly activated by treatment of the tongue with 1,2-tetradecarnoylphorbol-13-acetate (100 µM) twice in 1 day. In contrast, animals consuming a diet containing either ALA-DAG oil (7.5% or 30%), ALA-TAG oil (7.5% or 30%), or rapeseed oil (30%) for 4 weeks exhibited no significant differences in the cytosolic and membrane PKC activity in the lingual, esophageal, gastric, small intestinal, and colonic mucosa. Dose-related increases in PKC activity were not observed in the ALA-DAG oil-fed groups. Thus, the effects of dietary ALA-DAG oil on PKC activation in the digestive tract and lingual mucosa was similar to those of the ALA-TAG and rapeseed oils. These findings suggest that replacement of common dietary oil with ALA-DAG oil would not increase the risk of carcinogenesis.

Hyaluronan-degrading activity of mouse sperm hyaluronidase is not required for fertilization?

Sperm hyaluronidase has long been believed to participate in sperm penetration through the cumulus matrix. However, our previous works using male mice lacking either one of two sperm hyaluronidases, SPAM1 and HYAL5, conclusively showed that neither of these hyaluronidases is essential for fertilization. In this study, we examined whether the hyaluronan-degrading activity of mouse epididymal sperm is indeed required for the fertilization process. When the oocyte-cumulus complex was incubated with sperm protein extracts or capacitated epididymal sperm in the presence of the hyaluronidase inhibitor apigenin, dispersal of cumulus cells from the cumulus was effectively inhibited. Despite the presence of apigenin, capacitated epididymal sperm normally entered the oocyte-cumulus complex, traversed the cumulus matrix and reached the oocyte zona pellucida. Importantly, epididymal sperm were also capable of normally fertilizing the metaphase II-arrested oocytes in the presence of apigenin. These data suggest that the hyaluronan-degrading activity of sperm hyaluronidase may not be required for fertilization, at least in the mouse.