Health Sciences University of Hokkaido

Efficient elimination of apoptotic cells within epithelial cell sheets is crucial for preserving epithelial barrier integrity.¹ It is well established that immediate neighbors of an apoptotic cell actively participate in its removal by enclosing it within a wall of actomyosin, pushing it out in a purse-string manner in a process called apical extrusion.^2,3,4,5,6,7 Here, we found that sustained elevation of calcium ions in neighboring epithelial cells is necessary to generate the contractility required for apoptotic cell elimination. This phenomenon, which we call calcium response in effectors of apical extrusion (CaRE), highlights the disparate calcium dynamics within the epithelial sheet. Furthermore, we elucidate the essential role of desmosomes in CaRE. Specifically, we identify a subset of IP3 receptors within the endoplasmic reticulum that is recruited to the desmosome by K-Ras-induced actin-binding protein as the core component of this process. The interplay between these cellular structures heightens actomyosin contractility to drive apoptotic cell removal. Our findings underscore the physiological significance of integrating desmosomes with the endoplasmic reticulum in epithelial sheet homeostasis, shedding new light on cell-cell communication and tissue maintenance.

Previous neuroimaging studies have reported dual-task interference (DTi) and deterioration of task performance in a cognitive-motor dual task (DT) compared to that in a single task (ST). Greater frontoparietal activity is a neural signature of DTi; nonetheless, the underlying mechanism of cortical network in DTi still remains unclear. This study aimed to investigate the regional brain activity and neural network changes during DTi induced by highly demanding cognitive-motor DT. Thirty-four right-handed healthy young adults performed the spiral-drawing task. They underwent a paced auditory serial addition test (PASAT) simultaneously or independently while their cortical activity was measured using functional near-infrared spectroscopy. Motor performance was determined using the balanced integration score (BIS), a balanced index of drawing speed and precision. The cognitive task of the PASAT was administered with two difficulty levels defined by 1 s (PASAT-1 s) and 2 s (PASAT-2 s) intervals, allowing for the serial addition of numbers. Cognitive performance was determined using the percentage of correct responses. These motor and cognitive performances were significantly reduced during DT, which combined a drawing and a cognitive task at either difficulty level, compared to those in the corresponding ST conditions. The DT conditions were also characterized by significantly increased activity in the right dorsolateral prefrontal cortex (DLPFC) compared to that in the ST conditions. Multivariate Granger causality (GC) analysis of cortical activity in the selected frontoparietal regions of interest further revealed selective top-down causal connectivity from the right DLPFC to the right inferior parietal cortex during DTs. Furthermore, changes in the frontoparietal GC connectivity strength between the PASAT-2 s DT and ST conditions significantly correlated negatively with changes in the percentage of correct responses. Therefore, DTi can occur even in cognitively proficient young adults, and the right DLPFC and frontoparietal network being crucial neural mechanisms underlying DTi. These findings provide new insights into DTi and its underlying neural mechanisms and have implications for the clinical utility of cognitive-motor DTs applied to clinical populations with cognitive decline, such as those with psychiatric and brain disorders.

Oral cavity is an ecological niche for colonization of staphylococci, which are a major bacterial species causing community-acquired infections in humans. In this study, prevalence, and characteristics of staphylococci in oral cavity and skin of healthy individuals were investigated in northern Japan.

Saliva from oral cavity and swab from skin surface of hand were collected and cultured on selective media. Species of the isolates were identified genetically, and ST was determined for S. aureus and S. argenteus. Genes associated with antimicrobial resistance were detected by PCR.

Among 166 participants, a total of 75 S. aureus isolates were obtained from 61 individuals (37 %), and recovered more frequently in oral cavity (n = 48) than skin (n = 27). Among 23 STs identified in S. aureus isolates, ST8 (CC8), ST15 (CC15), and ST188 (CC1) were the most common (10 isolates each), with STs of CC1 being dominant (17 isolates). Methicillin-resistant S. aureus (MRSA) was isolated in the skin of two individuals and belonged to ST1 and ST6. Resistance to erythromycin and gentamicin associated with erm(A) and aac(6')-Ie-aph(2")-Ia, respectively, was more commonly found in ST5 and ST8 isolates. One S. argenteus isolate (ST2250, mecA-negative) was recovered from oral cavity of a participant (0.6 %). A total of 186 isolates of coagulase-negative staphylococci (CoNS) were recovered from 102 participants and identified into 14 species, with S. warneri being the most common (n = 52), followed by S. capitis (n = 42), S. saprophyticus (n = 20) and S. haemolyticus (n = 19). mecA was detected in S. saprophyticus, S. haemolyticus, and S. caprae, while arginine-catabolic mobile element (ACME) in only S. capitis and S. epidermidis.

S. aureus was more prevalent in oral cavity than skin surface, belonging to three major STs, with CC1 being a dominant lineage. The prevalence of antimicrobial resistance was distinct depending on CoNS species.