Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) ...through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall-associated proteins, including an antigen that stimulates mucosal T helper 17 (T
17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)-dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal T
17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota.
The evolution of humans brought about a co-occurring evolution of the human brain, which is far larger and more complex than that of many other organisms. The brain has evolved characteristically in ...humans in many respects, including macro-and micro-anatomical changes in the brain structure, changes in gene expression, and cell populations and ratios. These characteristics are essential for the execution of higher functions, such as sociality, language, and cognition, which express humanity, and are thought to have been acquired over evolutionary time. However, with the acquisition of higher functions also comes the risk of the disease in which they fail. This review focuses on human brain evolution and neurodevelopmental disorders (NDDs) and discusses brain development, molecular evolution, and human brain evolution. Discussing the potential for the development and pathophysiology of NDDs acquired by human brain evolution will provide insights into the acquisition and breakdown of higher functions from a new perspective.
We aimed to investigate the relationship between the risk of oral frailty and awareness of oral frailty among Japanese adults in an adult dental health field study conducted in Kanagawa Prefecture. ...Questionnaire data from a total of 5051 individuals (1907 males, 3144 females; mean age; 59.9 years) were used. The risk of oral frailty was assessed using the Oral Frailty Index-8. Of the participants, 1418 (28.1%) had a high risk of oral frailty and 1495 (29.6%) had knowledge of oral frailty. Logistic regression analysis indicated that the risk of oral frailty was significantly associated with awareness of oral frailty. We further found that awareness of oral frailty was significantly related to gender (female), age (20-39 compared to 70-79, ≥ 80), residential areas (Yokohama compared to Kawasaki, Sagamihara), exercise habits (yes), eating a balanced diet (yes), consciousness of oral health (yes), risk of oral frailty (low) and outpatient category (hospital visit). For groups with low levels of awareness obtained from the results of this study, it is necessary to consider the means of accessibility and increase awareness further.
Oral microbiota play a pivotal role in maintaining homeostasis, safeguarding the oral cavity, and preventing the onset of disease. Oral dysbiosis has the potential to trigger pro-inflammatory effects ...and immune dysregulation, which can have a negative impact on systemic health. It is regarded as a key etiological factor for periodontitis. The emergence and persistence of oral dysbiosis have been demonstrated to mediate inflammatory pathology locally and at distant sites. The heightened inflammation observed in oral dysbiosis is dependent upon the secretion of interleukin-17A (IL-17A) by various innate and adaptive immune cells. IL-17A has been found to play a significant role in host defense mechanisms by inducing antibacterial peptides, recruiting neutrophils, and promoting local inflammation via cytokines and chemokines. This review seeks to present the current knowledge on oral dysbiosis and its prevention, as well as the underlying role of IL-17A in periodontitis induced by oral dysbiosis and its impact on systemic inflammatory disease.
Development of periodontal disease (PD) may be affected by socioeconomic status. This study examined the relationship between occupational status and PD in a 5-year prospective cohort of Japanese ...workers.
In total, 19,633 participants had initial examinations at the Aichi Health Promotion Foundation, of whom 8210 participants aged 20 years or older did not have PD. Follow-up examinations were conducted for 3757 participants, accounting for 45.8% of baseline participants. Ultimately, 3390 participants were analyzed according to the criterion of job classification at baseline, which was based on the International Standard Classification of Occupations, 1987. Oral examinations were performed using the Community Periodontal Index (CPI). The CPI scores were coded as follows: healthy (score of 0); bleeding after probing (1); dental calculus (2); shallow pockets (3); and deep pockets (4). Participants with one or more sextants with a score >2 were diagnosed with PD. Poisson regression analysis was performed to adjust for age and other potential confounders.
Overall, 31.6% of men and 23.8% of women had developed PD (CPI scores of 3 or 4). The adjusted relative risk (RR) for PD (CPI scores of 3 or 4) in men was not significant. On the other hand, the adjusted RRs for PD (CPI score of 4) in men were 2.52-, 2.39-, and 2.74-fold higher for skilled workers, sales persons, and drivers, respectively, than for professionals. In contrast, we found no gradient in women.
We found a gradient related to the risk of developing PD according to occupational status among men in a Japanese worker population.
•The first cohort study to evaluate occupational status and periodontal disease.•Revealed occupational status affects developing periodontal disease over 5 years.•Skilled workers, sale persons, and drivers had higher risks of periodontal disease.
Although many epidemiologic surveys have shown that gingivitis is more prevalent in males than in females, few studies have clearly explained what causes this difference. The objective of the present ...study is to explain the sex difference in gingivitis based on the interaction between oral health behaviors and related factors, such as knowledge, attitude, and lifestyle, in young people.
The study was comprised of 838 subjects (440 males and 398 females), aged 18 and 19 years. Gingivitis was assessed by the percentage of bleeding on probing (%BOP). Additional information was collected regarding oral hygiene status, oral health behaviors, and related factors. Structural equation modeling was used to test pathways from these factors to %BOP. Multiple-group modeling was also conducted to test for sex differences.
Females had greater knowledge, a more positive attitude, a healthier lifestyle, and higher level of oral health behaviors than males. There were significant differences in the paths (i.e., from lifestyle, knowledge, and attitude to %BOP) through oral health behaviors and oral health status.
Sex-based differences in gingivitis in young people can be explained by oral health behaviors and hygiene status, which are influenced by lifestyle, knowledge, and attitude. To prevent gingivitis, different approaches to males and females may be useful.
Septal nuclei are telencephalic structures associated with a variety of brain functions as part of the limbic system. The two posterior septal nuclei, the triangular septal nucleus (TS) and the bed ...nuclei of the anterior commissure (BAC), are involved in fear and anxiety through their projections to the medial habenular nucleus. However, the development of both the TS and BAC remains unclear. Here, we found a novel caudal origin and putative migratory stream of mouse posterior septal neurons arising from the thalamic eminence (TE), a transient developmental structure at the rostral end of the rodent diencephalon. TE-derived cells, which have glutamatergic identity, migrated rostrally and entered the telencephalic territory by passing beneath the third ventricle. Subsequently, they turned dorsally toward the posterior septum. We also observed that TS and BAC neurons in the postnatal septum were labeled with GFP by in utero electroporation into the TE, suggesting a shared origin. Furthermore, TE-derived septal neurons migrated along the fornix, an efferent pathway from the hippocampus. These results demonstrate that posterior septal neurons have a distinct extratelencephalic origin from other septal nuclei. This heterogeneous origin may contribute to neuronal diversity of the septal nuclear complex.
Rett syndrome (RTT) is a neurodevelopmental disorder caused by MECP2 mutations. Although emerging evidence suggests that MeCP2 deficiency is associated with dysregulation of mechanistic target of ...rapamycin (mTOR), which functions as a hub for various signaling pathways, the mechanism underlying this association and the molecular pathophysiology of RTT remain elusive. We show here that MeCP2 promotes the posttranscriptional processing of particular microRNAs (miRNAs) as a component of the microprocessor Drosha complex. Among the MeCP2-regulated miRNAs, we found that miR-199a positively controls mTOR signaling by targeting inhibitors for mTOR signaling. miR-199a and its targets have opposite effects on mTOR activity, ameliorating and inducing RTT neuronal phenotypes, respectively. Furthermore, genetic deletion of miR-199a-2 led to a reduction of mTOR activity in the brain and recapitulated numerous RTT phenotypes in mice. Together, these findings establish miR-199a as a critical downstream target of MeCP2 in RTT pathogenesis by linking MeCP2 with mTOR signaling.
Display omitted
•MeCP2 facilitates the processing of miR-199a as a component of the Drosha complex•miR-199a ameliorates RTT neuronal phenotypes and its inhibition blocks MeCP2 function•miR-199a positively controls mTOR signaling by targeting mTOR signaling inhibitors•Genetic deletion of miR-199a-2 recapitulates numerous RTT phenotypes
Tsujimura et al. find that MeCP2 facilitates processing of miR-199a, which, in turn, leads to upregulation of mTOR signaling. Genetic deletion of miR-199a-2 recapitulates RTT phenotypes, suggesting that the MeCP2/miR-199a/mTOR axis may contribute to RTT pathophysiology.
Rett syndrome (RTT) is a severe neurological disorder, with impaired brain development caused by mutations in MECP2; however, the underlying mechanism remains elusive. We know from previous work that ...MeCP2 facilitates the processing of a specific microRNA, miR-199a, by associating with the Drosha complex to regulate neuronal functions. Here, we show that the MeCP2/miR-199a axis regulates neural stem/precursor cell (NS/PC) differentiation. A shift occurs from neuronal to astrocytic differentiation of MeCP2- and miR-199a-deficient NS/PCs due to the upregulation of a miR-199a target, Smad1, a downstream transcription factor of bone morphogenetic protein (BMP) signaling. Moreover, miR-199a expression and treatment with BMP inhibitors rectify the differentiation of RTT patient-derived NS/PCs and development of brain organoids, respectively, suggesting that facilitation of BMP signaling accounts for the impaired RTT brain development. Our study illuminates the molecular pathology of RTT and reveals the MeCP2/miR-199a/Smad1 axis as a potential therapeutic target for RTT.
Display omitted
•The MeCP2-downstream microRNA miR-199a regulates NS/PC differentiation•miR-199a expression ameliorates impaired differentiation of MeCP2-deficient NS/PCs•miR-199a reduces protein abundance of the BMP-downstream transcription factor Smad1•BMP inhibitors correct the development of Rett patient-derived brain organoids
Nakashima et al. reveal that the MeCP2-downstream miR-199a regulates NS/PC differentiation. The expression of miR-199a, via the downregulation of Smad1, or treatment with BMP inhibitors rescues patients with RTT-derived NS/PCs differentiation and organoid development, suggesting that overactive BMP signaling accounts for the impaired brain development in RTT.
Recent studies suggest that the commensal microbiota affects not only host energy metabolism and development of immunity but also bone remodeling by positive regulation of osteoclast activity. ...However, the mechanism of regulation of bone cells by the commensal microbiota has not been elucidated. In this study, 8-week-old specific pathogen-free (SPF) and germ-free (GF) mice were compared in terms of alveolar bones and primary osteoblasts isolated from calvarias. Micro-CT analysis showed that SPF mice had larger body size associated with lower bone mineral density and bone volume fraction in alveolar bones compared with GF mice. Greater numbers of osteoclasts in alveolar bone and higher serum levels of tartrate-resistant acid phosphatase 5b were observed in SPF mice. Tissue extracts from SPF alveolar bone showed higher levels of cathepsin K, indicating higher osteoclast activity. SPF alveolar extracts also showed elevated levels of γ-carboxylated glutamic acid⁻osteocalcin as a marker of mature osteoblasts compared with GF mice. Polymerase chain reaction (PCR) array analysis of RNA directly isolated from alveolar bone showed that in SPF mice, expression of mRNA of
, which also acts as an inhibitor of bone mineralization, was strongly enhanced compared with GF mice. Cultured calvarial osteoblasts from SPF mice showed reduced mineralization but significantly enhanced expression of mRNAs of
, and decreased ratio of
compared with GF mice. Furthermore, PCR array analyses of transcription factors in cultured calvarial osteoblasts showed strongly upregulated expression of
. In contrast,
was strongly downregulated in SPF osteoblasts. These results suggest that the commensal microbiota prevents excessive mineralization possibly by stimulating osteocalcin expression in osteoblasts, and enhances both osteoblast and osteoclast activity by regulating specific transcription factors.
PDF
