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The chromosome mis-segregation assay showed that variants did not have any effects on mitosis. Injecting TRIP13 cRNA into oocytes from one affected individual was able to rescue the phenotype, which has implications for future therapeutic treatments. This study reports pathogenic variants in TRIP13 responsible for oocyte meiotic arrest, and it highlights the pivotal but different roles of TRIP13 in meiosis and mitosis. These findings also indicate that different dosage effects of mutant TRIP13 might result in two distinct human diseases.Nuclear size plays pivotal roles in gene expression, embryo development, and disease. A central hypothesis in organisms ranging from yeast to vertebrates is that nuclear size scales to cell size. selleck products This implies that nuclei may reach steady-state sizes set by limiting cytoplasmic pools of size-regulating components. By monitoring nuclear dynamics in early sea urchin embryos, we found that nuclei undergo substantial growth in each interphase, reaching a maximal size prior to mitosis that declined steadily over the course of development. Manipulations of cytoplasmic volume through multiple chemical and physical means ruled out cell size as a major determinant of nuclear size and growth. Rather, our data suggest that the perinuclear endoplasmic reticulum, accumulated through dynein activity, serves as a limiting membrane pool that sets nuclear surface growth rate. Partitioning of this local pool at each cell division modulates nuclear growth kinetics and dictates size scaling throughout early development.Neutrophils represent the most abundant cell type in peripheral blood and exhibit a remarkably brief (6-8 h) half-life in circulation. The fundamental role of these professional phagocytes has been established in acute inflammation, based on their potential to both initiate and receive inflammatory signals. Furthermore, neutrophils also take part in maintaining chronic inflammatory processes, such as in various autoimmune diseases. Here, we demonstrate that human autologous apoptotic neutrophils are readily engulfed by immature monocyte-derived dendritic cells (moDCs) with similar efficiency as allogeneic apoptotic neutrophils [Majai G et al. (2010) J Leukoc Biol 88, 981-991]. Interestingly, in contrast to the allogeneic system, exposure of moDCs to autologous apoptotic neutrophils inhibits LPS + IFN-γ-induced production of inflammatory cytokines in a phagocytosis-independent manner. Autologous apoptotic neutrophil-primed DCs are able to modulate T-cell responses by inducing the generation of IFN-γ-secreting cells while hampering that of IL-17A-producing cells. Our observations indicate that capture of autologous apoptotic neutrophils by immature DCs may impede further neutrophil-mediated phagocytosis and tissue damage, and allow increased clearance of dying cells by macrophages.Compared to two-photon excitation (2PE) microscopy, three-photon excitation (3PE) microscopy has superior spatial resolution, deeper tissue penetration, and less defocused interference, and is, therefore, of great interest in the field of bioimaging. The design of suitable agents which can meet the various needs of the technology, such as large Stokes shift, good three-photon absorption (3PA), subcellular targeting, and fluorescence lifetime imaging (FLIM) properties, is a formidable challenge. In order to address this, two iridium(III) complexes (3PAIr1 and 3PAIr2) were developed as efficient three-photon phosphorescence (3PP) agents for bioimaging. Theoretical calculations reveal that the introduction of a new group to the molecular scaffold confers a quadruple promotion in three-photon transition probability. Herein, the confocal and lifetime imaging of mitochondria as using Ir(III) complexes as 3PP agents is demonstrated for the first time. The complexes exhibit the advantages of low working concentration (50 nM), fast uptake (5 min), and low threshold for three-photon excitation power (ca. 0.5 mW at 980 nm). Moreover, the impressive tissue penetration depth achieved with these 3PA agents (ca. 450 µm) allowed the 3D imaging and reconstruction of brain vasculature from a living specimen. These results indicate that the Ir(III) complexes are highly promising for medical imaging applications.Background Although the prevalence of gastroesophageal reflux disease (GERD) has been increasing in Japan, little is known concerning the prevalence and severity of GERD in pediatric patients. This study compared the prevalence and severity of endoscopically proven GERD in pediatric patients over a 15-year period seen at an endoscopy center in Japan. Methods This was a retrospective chart review of Japanese children between the ages of 5 and 18 years undergoing esophagogastroduodenoscopy for upper gastrointestinal symptoms or anemia between 2005 and 2019. The prevalence and severity of reflux esophagitis and endoscopic Barrett’s esophagus were compared between 2005-2012 and 2013-2019. Results A total of 564 patients were evaluated; 315 from 2005 to 2012 [average age, 13.8 (range, 5-18) years; 147 boys] and 249 from 2013 to 2019 [average age, 14.7 (range, 5-18) years; 108 boys]. Demographics and clinical features were similar between the two groups. The proportion with erosive esophagitis or endoscopic Barrett’s esophagus increased significantly between the two periods (9.8% to 18.1% for GERD, P=0.0045 and 2.5% to 9.6 % for Barrett’s, P=0.0003). The proportion of GERD patients with endoscopic Barrett’s esophagus also significantly increased between the two periods [i.e., 53.3% (24/45) vs. 25.8% (8/31), P=0.017]. Conclusion The prevalence and severity of endoscopically proven GERDs has significantly increased over the past 15 years at an endoscopy center in Japan. Detailed population based studies are needed to assess whether this is occurring throughout Japan.Background The intestinal microbiota and its metabolites have been reported to play an important role in stroke. Gut microbiota-originating short-chain fatty acids (SCFAs) modulate brain functions directly or indirectly through immune, endocrine, vagal, and other humoral pathways. However, relatively few investigations have evaluated the gut microbiome and SCFAs spectrum or their potential associations with stroke outcomes in acute ischemic stroke (AIS) patients with different stroke severities. Methods We used 16S rRNA gene sequencing and gas chromatography to compare the fecal microbial composition and SCFA spectrum between AIS patients (n = 140) and healthy controls (n = 92). Their associations with 90-day poor functional outcomes were evaluated by logistic regression models. Results We found that the intestinal microbiota distinguished AIS patients from healthy controls. A lack of SCFAs-producing bacteria and a low fecal SCFAs level defined dysbiosis in AIS patients, especially those with increased stroke severity.