Characteristics of claudin expression in follicle-associated epithelium of Peyer's patches: Preferential localization of claudin-4 at the apex of the dome region

Gut-associated lymphoreticular tissue (GALT), such as Peyer's patches (PP) and cecal patches, are important inductive sites for mucosal immune responses. As such, the GALT may have an epithelial barrier different from that of villous epithelium. In this study, we investigated the immunohistochemical distribution of the claudin family and occludin in the follicle-associated epithelium (FAE) of Peyer's patches and cecal patches of murine intestine. Unique profiles of claudin-2, -3, -4 and occludin expression were noted in the tight junctions of the FAE: claudin-4 was preferentially expressed in the apex region; claudin-2 was only weakly expressed on the crypt side of the FAE compared to stronger expression on the crypt side of villous epithelial cells; claudin-3 and occludin were found throughout the dome. These unique expression patterns were present also in cecal patch FAE. We also found that claudin-4 expression in the FAE of Peyer's patches and cecal patches corresponded with the presence of TUNEL-positive apoptotic cells, and Peyer's patch-deficient mice had expression patterns of claudin and occludin in villous epithelia similar to those in wild-type mice. We conclude that claudin-4 expression is preferentially associated with the dome region of FAE, the mucosal inductive site of the murine intestine. In that location and it might correlate with the cell life cycle, help maintain the apex configuration of the dome, or be a factor favoring the uptake of antigens by the FAE

Current status and problems of elderly drivers in our outpatient clinic

　当院では平成29年３月12日の道路交通法改正を踏まえて平成29年４月より，もの忘れ外来とは別に「運転免許外来」を新設し，時間をかけた丁寧な診療と告知，指導，運転免許返納後の生活確保・支援ができるよう，多職種で受診者に対応している．平成31年４月までの運転免許外来受診者は31人で，平均年齢80.07±3.91歳．第一分類該当者19人，交通違反での紹介３人で，その他は自発的な受診であった．10例は既に事故を起こし，６例は既に抗認知症薬を内服していた . 受診者のほとんどが，通院，買い物，農作業など運転中止後の生活が困るとの理由から，運転継続を希望した．神経心理検査では，MMSE-J 22.32/30±3.87, Kohs IQ 66.42±11.87, DASC-21 29.53±7.07, CDR 0.58±0.19と比較的認知機能低下が軽度な者が多かった．頭部 MRI では20例に陳旧性脳梗塞や脳挫傷，12例に脳萎縮を認め，123I-IMP 脳血流 SPECT では14例にアルツハイマー病を示唆する脳血流低下を認めた．診断後，全例に運転免許返納を推奨したが，自発的に運転中止に至った例は９例のみであった．かかりつけ医による診断書作成が普及し自主返納事例も増加したためか，当院の受診者数ならびに運転免許取り消し処分となる事例は外来開設当初の予想より少なかった．認知機能低下は認めるものの明らかな認知症に至っていない MCI 症例については，診断書提出後も運転継続している事例が多かった．運転継続希望者に丁寧に現制度の意義を説明し，移動手段の確保や生活支援について地域で相談できる体制作りが必要である．　Following the revision of the Road Traffic Act, which obligates elderly drivers to undergo cognitive screening tests at license renewal, we established a new outpatient memory clinic specializing in issues surrounding elderly drivers’ driver licenses. In this new outpatient clinic, we provide guidance and information about supporting resources for life after returning their driver’s licenses and the usual medical care and education. In the past two years, 31 patients, with an average age of 80.1±3.9 years, visited this clinic. Among these, 19 were referred to our clinic because of impaired cognition by screening test (the first classification), three were referred us for traffic violations and the others visited voluntarily. Among these 31 patients, ten had already experienced car accidents and six had already been prescribed cholinesterase inhibitors. Neuropsychological examination revealed mildly impaired cognitive function including MMSE-J 22.3±3.9, Kohs IQ 66.4±11.9, DASC-21 29.5±7.1 and CDR 0.58 ±0.19. Brain MRI revealed significant brain atrophy in 20 patients and brain contusions in 12. 123I-IMP SPECT showed decreased cerebral blood flow in 14 patients. Although driving is necessary for most patients to maintain activities of daily living and quality of life, we recommended all to stop driving based on the revised Road Traffic Act, which restricts driving by people with dementia. However, only nine patients suspended their driving and returned their licenses voluntarily; most MCI patients continued driving even after diagnosis. More effort is necessary to persuade patients of the significance of the current system, as is a social system that offers alternative means of transportation and supports patients in their lives in their local community

Chemo-Enzymatic Synthesis of 1’-Photoreactive Sucrose Derivatives via Ether Linkage

As the 1’-hydroxyl group of sucrose is well known to be less reactive than other primary alcohols, there are no reports on the substitution of a phenoxy group at this position. Chemo-enzymatic synthesis of photoreactive 1’-phenoxy-substituted sucrose was examined to elucidate the functional analysis of sweet receptors

Cytoplasmic Kinase Network Mediates Defense Response to <i>Spodoptera litura</i> in Arabidopsis

Plants defend against folivores by responding to folivore-derived elicitors following activation of signaling cascade networks. In Arabidopsis, HAK1, a receptor-like kinase, responds to polysaccharide elicitors (Frα) that are present in oral secretions of Spodoptera litura larvae to upregulate defense genes (e.g., PDF1.2) mediated through downstream cytoplasmic kinase PBL27. Here, we explored whether other protein kinases, including CPKs and CRKs, function with PBL27 in the intracellular signaling network for anti-herbivore responses. We showed that CRK2 and CRK3 were found to interact with PBL27, but CPKs did not. Although transcripts of PDF1.2 were upregulated in leaves of wild-type Arabidopsis plants in response to mechanical damage with Frα, this failed in CRK2- and PBL27-deficient mutant plants, indicating that the CRK2/PBL27 system is predominantly responsible for the Frα-responsive transcription of PDF1.2 in S. litura-damaged plants. In addition to CRK2-phosphorylated ERF13, as shown previously, ethylene signaling in connection to CRK2-phosphorylated PBL27 was predicted to be responsible for transcriptional regulation of a gene for ethylene response factor 13 (ERF13). Taken together, these findings show that CRK2 regulates not only ERF13 phosphorylation but also PBL27-dependent de novo synthesis of ERF13, thus determining active defense traits against S. litura larvae via transcriptional regulation of PDF1.2

Arabidopsis Phosphatidic Acid Phosphohydrolases Are Essential for Growth under Nitrogen-Depleted Conditions

The Arabidopsis homologs of mammalian lipin, PAH1 and PAH2, are cytosolic phosphatidic acid phosphohydrolases that are involved in phospholipid biosynthesis and are essential for growth under phosphate starvation. Here, pah1 pah2 double-knockout mutants were found to be hypersensitive to nitrogen (N) starvation, whereas transgenic plants overexpressing PAH1 or PAH2 in the pah1 pah2 mutant background showed a similar growth phenotype as compared with wild type (WT) under N starvation. The chlorophyll content of pah1 pah2 was significantly lower than that of WT, whereas the chlorophyll content and photosynthetic activity of the transgenic plants were significantly higher than those of WT under N-depleted conditions. Membrane glycerolipid composition of the pah1 pah2 mutants showed a significant decrease in the mole percent of chloroplast lipids to other phospholipids, whereas membrane lipid composition did not differ between transgenic plants and WT plants. Pulse-chase labeling experiments using plants grown under N-depleted conditions showed that, in pah1 pah2 plants, the labeling percent of chloroplast lipids such as phosphatidylglycerol and monogalactosyldiacylglycerol in the total glycerolipids was significantly lower than in WT. Moreover, N starvation-induced degradation of chloroplast structure was enhanced in pah1 pah2 mutants, and the membrane structure was recovered by complementation with PAH1. Thus, PAH is involved in maintaining chloroplast membrane structure and is required for growth under N-depleted conditions

Association of daily physical activity and leisure-time exercise with dysphagia risk in community-dwelling older adults: a cross-sectional study

Abstract This study aimed to clarify the association of daily physical activity and leisure-time exercise with the risk of dysphagia in community-dwelling Japanese older adults using a questionnaire-based survey. We analyzed 3070 participants (1657 men, 1413 women; age 66 ± 4 years [mean ± SD]) of the Shizuoka and Daiko studies within the Japanese Multi-Institutional Collaborative Cohort study. We used the Dysphagia Risk Assessment for the Community-dwelling Elderly questionnaire to assess dysphagia risk and the International Physical Activity Questionnaire to assess daily physical activity and leisure-time exercise. Logistic regression analyses were used to evaluate the independent association of the amount of physical activity and leisure-time exercise with dysphagia risk. The proportion of participants with dysphagia risk was 27.5% (n = 844) and the risk was significantly higher in women (29.8%, n = 421) than in men (25.5%, n = 423; P = 0.008). Daily physical activity was not associated with dysphagia risk. A greater amount of leisure-time exercise was associated with lower dysphagia risk (P for trend = 0.003) and individuals in the highest leisure-time exercise quartile had a significantly lower odds ratio (0.68, 95% CI 0.52–0.89) than those in the lowest quartile, even after adjusting for the covariates

Fission Yeast Pot1 and RecQ Helicase Are Required for Efficient Chromosome Segregation▿

Pot1 is a single-stranded telomere-binding protein that is conserved from fission yeast to mammals. Deletion of Schizosaccharomyces pombe pot1+ causes immediate telomere loss. S. pombe Rqh1 is a homolog of the human RecQ helicase WRN, which plays essential roles in the maintenance of genomic stability. Here, we demonstrate that a pot1Δ rqh1-hd (helicase-dead) double mutant maintains telomeres that are dependent on Rad51-mediated homologous recombination. Interestingly, the pot1Δ rqh1-hd double mutant displays a “cut” (cell untimely torn) phenotype and is sensitive to the antimicrotubule drug thiabendazole (TBZ). Moreover, the chromosome ends of the double mutant do not enter the pulsed-field electrophoresis gel. These results suggest that the entangled chromosome ends in the pot1Δ rqh1-hd double mutant inhibit chromosome segregation, signifying that Pot1 and Rqh1 are required for efficient chromosome segregation. We also found that POT1 knockdown, WRN-deficient human cells are sensitive to the antimicrotubule drug vinblastine, implying that some of the functions of S. pombe Pot1 and Rqh1 may be conserved in their respective human counterparts POT1 and WRN