•Septins are conserved cytoskeletal GTP-binding proteins.•Septins regulate the proliferation of neural progenitor cells and neuritogenesis.•Septins also coordinate synapse formation and regulations.
...Morphogenetic processes during brain development and postdevelopmental remodeling of neural architecture depend on the exquisite interplay between the microtubule- and actin-based cytoskeletal systems. Accumulation of evidence indicates cooperative roles of another cytoskeletal system composed of the septin family. Here we overview experimental findings on mammalian septins and their hypothetical roles in the proliferation of neural progenitor cells, neurite development, synapse formation and regulations. The diverse, mostly unexpected phenotypes obtained from gain- and loss-of-function mutants point to unknown molecular network to be elucidated, which may underlie pathogenetic processes of infectious diseases and neuropsychiatric disorders in humans.
Assembly of Mammalian Septins Kinoshita, Makoto
Journal of biochemistry (Tokyo),
10/2003, Volume:
134, Issue:
4
Journal Article
Peer reviewed
Septins are a conserved family of polymerizing guanine nucleotide binding proteins associated with diverse processes in dividing and non-dividing cells. In humans, 12 septin genes generate dozens of ...polypeptides, many of which comprise heterooligomeric complexes. Native and recombinant mammalian septin complexes are purified as ~8-nm-thick filaments of variable length. Ultrastructurally, a mammalian septin filament appears an irregular array of structural segments, whose polarity is obscure. The filaments have a potential to self-assemble into higher-order structures by lateral stacking and tandem annealing, eventually forming uniformly curved bundles, i.e., rings and coils. The septin filaments also undergo templated assembly along existing actin bundles containing an adapter protein, anillin. The resultant higher-order assembly of septin filaments may provide scaffolds to recruit other molecules and/or help organize the actin-based structures. The in vitro self-assembly is an irreversible process, which is not coupled with robust nucleotide exchange or hydrolysis. In contrast, septin-based structures rearrange and disassemble in cells, which might be controlled by diverse factors (e.g., the Cdc42-borg system, anillin, syntaxin, phospholipids) and covalent modifications (e.g., phosphorylation, ubiquitination, sumoylation). An immediate goal of septin biochemistry is to define the mechanisms of assembly and disassembly of this elusive cytoskeleton.
Microbiota have been shown to have a great influence on functions of intestinal epithelial cells (ECs). The role of indole as a quorum-sensing (QS) molecule mediating intercellular signals in ...bacteria has been well appreciated. However, it remains unknown whether indole has beneficial effects on maintaining intestinal barriers in vivo. In this study, we analyzed the effect of indole on ECs using a germ free (GF) mouse model. GF mice showed decreased expression of junctional complex molecules in colonic ECs. The feces of specific pathogen-free (SPF) mice contained a high amount of indole; however the amount was significantly decreased in the feces of GF mice by 27-fold. Oral administration of indole-containing capsules resulted in increased expression of both tight junction (TJ)- and adherens junction (AJ)-associated molecules in colonic ECs in GF mice. In accordance with the increased expression of these junctional complex molecules, GF mice given indole-containing capsules showed higher resistance to dextran sodium sulfate (DSS)-induced colitis. A similar protective effect of indole on DSS-induced epithelial damage was also observed in mice bred in SPF conditions. These findings highlight the beneficial role of indole in establishing an epithelial barrier in vivo.
Background:Outcomes of cryoballoon ablation for persistent atrial fibrillation (AF) are unclear, especially in Japanese patients, so the effectiveness and safety of cryoballoon ablation in clinical ...practice were retrospectively compared with those of contact force-sensing radiofrequency (CFRF) ablation including the high-power protocol.Methods and Results:Consecutive patients with persistent AF were reviewed, and 253 and 265 patients who underwent cryoballoon and CFRF ablation, respectively, were enrolled. The primary endpoint was atrial arrhythmia recurrence. The secondary endpoints were periprocedural complications and repeat ablation. The rate of additional left atrial (LA) ablation after pulmonary vein isolation (PVI) was similar between groups (68.8% cryoballoon vs. 74.0% CFRF, P=0.19). Freedom from atrial arrhythmia recurrence was comparable between groups over a follow-up of 25.5±12.5 months (72.3% cryoballoon vs. 69.8% CFRF; adjusted hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.59–1.21, P=0.36). Outcomes were similar in the subgroups of PVI alone and PVI plus additional LA ablation. LA posterior wall isolation, absence of defragmentation, and low creatine clearance, but not catheter selection, were associated with the primary endpoint. Periprocedural complications (adjusted HR 0.73, 95% CI 0.34–1.54, P=0.41) and repeat ablation (adjusted HR 1.11, 95% CI 0.71–1.74, P=0.64) were similar for both procedures.Conclusions:Cryoballoon ablation for persistent AF in Japanese clinical practice had acceptable outcomes comparable to those of advanced CFRF ablation.
Oxidative stress causes tissue damage, affecting age-related pathologies. Protein restriction (PR) provides a powerful intervention strategy for reducing oxidative stress, which may have a positive ...effect on individual organs. However, it is unknown whether PR intervention influences the olfactory system. Here, we investigated how 10 months of PR could affect the cell dynamics of the olfactory epithelium (OE) in mice. We found that PR reduced age-related loss of outer hair cells in the cochlea, providing preventive effects against age-related hearing loss. In contrast, PR resulted in reduced mature olfactory sensory neurons (OSNs), increased proliferative basal cells, and increased apoptotic OSNs in zone 1 (the only area containing neurons expressing NQO1 quinone dehydrogenase 1) of the OE in comparison with animals given a control diet. Substantial oxidative stress occurred in NQO1-positive cells and induced apoptotic OSNs in zone 1. These results indicate that in contrast to the positive effect on the auditory system, PR induces oxidative stress and structurally and functionally negative effects on OSNs in zone 1, which is probably involved in the bioactivation of NQO1.
Exposure to fine particulate matter (PM2.5) is a potential aggravating factor for respiratory and allergic diseases. However, which PM2.5 sources are associated with such diseases remains unclear. ...This study aimed to investigate the association of PM2.5 sources with allergic and respiratory symptoms in schoolchildren. PM2.5 samples were collected in Fukuoka during the spring in 2014 and 2015. Asian dust was observed in 2014. Ion components, elemental components, and organic components were analyzed. Positive matrix factorization (PMF) was conducted to calculate PM2.5 concentrations from each source. Mixed logistic regression analysis with a random intercept for each schoolchild was performed to evaluate the association of components and sources with symptoms. Among 2317 schoolchildren, the mean prevalence was 28.9%, 23.6%, 11.2%, and 11.4% for lower respiratory, nasal, ocular, and skin symptoms, respectively. PMF identified the following six PM2.5 sources “Secondary sulfate and coal combustion”, “Secondary nitrate”, “Heavy oil combustion”, “Sea salt”, “Soil” and “Traffic emission”. An interquartile range of PM2.5 mass was associated with nasal (Odds ratios 1.08, 95% confidence interval 1.03, 1.13), ocular (1.10, 1.04, 1.16), and skin symptoms (1.13, 1.06, 1.20). Among the source factors, “Heavy oil combustion” was significantly associated with nasal symptom (1.11, 1.05, 1.18) while “Sea salt” was associated with nasal (1.06, 1.02, 1.11) and skin (1.073, 1.01, 1.14) symptoms. We found “Soil”, which might be affected by Asian dust, was associated with ocular (1.07, 1.03, 1.10) and skin (1.05, 1.01, 1.08) symptoms. Further studies in other seasons or places are needed to clarify the influence of PM2.5 sources on children's health.
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•PM2.5 in Fukuoka is affected both by local emission and transported particles.•PM2.5 mass increased allergic but not lower respiratory symptoms for children.•Soil influenced by Asian dust may cause ocular and skin symptom.•Heavy oil combustion from ship emission/aged sea salt linked with nasal symptoms.
Vestibular dysfunction causes postural instability, which is prevalent in the elderly. We previously showed that an imperceptible level of noisy galvanic vestibular stimulation (nGVS) can improve ...postural stability in patients with bilateral vestibulopathy during the stimulus, presumably by enhancing vestibular information processing. In this study, we investigated the after-effects of an imperceptible long-duration nGVS on body balance in elderly adults. Thirty elderly participants underwent two nGVS sessions in a randomised order. In Session 1, participants received nGVS for 30 min twice with a 4-h interval. In Session 2, participants received nGVS for 3 h. Two-legged stance tasks were performed with eyes closed while participants stood on a foam rubber surface, with and without nGVS, and parameters related to postural stability were measured using posturography. In both sessions, the postural stability was markedly improved for more than 2 h after the cessation of the stimulus and tended to decrease thereafter. The second stimulation in Session 1 caused a moderate additional improvement in body balance and promoted the sustainability of the improvement. These results suggest that nGVS can lead to a postural stability improvement in elderly adults that lasts for several hours after the cessation of the stimulus, probably via vestibular neuroplasticity.
Recently accumulating evidence identified the disease entity where astrocytes residing within the central nervous system (CNS) are the target of autoantibody-mediated autoimmunity. Aquaporin4 (AQP4) ...is the most common antigen to serve as astrocyte-targeted autoimmune responses. Here, in this review, the clinical and pathological aspects of AQP4-mediated astrocyte disease are discussed together with the pathogenic role of anti-AQP4 antibody. More recently, the mechanism of immune dysregulation resulting in the production of astrocyte-targeted autoantibody is also revealed, and the postulated hypothesis is discussed.
Colonic epithelial cells are covered by thick inner and outer mucus layers. The inner mucus layer is free of commensal microbiota, which contributes to the maintenance of gut homeostasis. In the ...small intestine, molecules critical for prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti-microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have been identified. Although there are mucus layers providing physical barriers against the large number of microbiota present in the large intestine, the mechanisms that separate bacteria and colonic epithelia are not fully elucidated. Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively expressed in epithelial cells at the uppermost layer of the large intestinal gland, was secreted into the lumen and bound flagellated bacteria including Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner mucus layer and many flagellated bacteria invaded epithelia. Lypd8(-/-) mice were highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the bacterial-free state of the inner mucus layer and ameliorated DSS-induced intestinal inflammation in Lypd8(-/-) mice. Lypd8 bound to flagella and suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of intestinal bacteria and epithelial cells in the colon to preserve intestinal homeostasis.
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