Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization

RBM20 is a major regulator of heart-specific alternative pre-mRNA splicing of TTN encoding a giant sarcomeric protein titin. Mutation in RBM20 is linked to autosomal-dominant familial dilated cardiomyopathy (DCM), yet most of the RBM20 missense mutations in familial and sporadic cases were mapped to an RSRSP stretch in an arginine/serine-rich region of which function remains unknown. In the present study, we identified an R634W missense mutation within the stretch and a G1031X nonsense mutation in cohorts of DCM patients. We demonstrate that the two serine residues in the RSRSP stretch are constitutively phosphorylated and mutations in the stretch disturb nuclear localization of RBM20. Rbm20 S637A knock-in mouse mimicking an S635A mutation reported in a familial case showed a remarkable effect on titin isoform expression like in a patient carrying the mutation. These results revealed the function of the RSRSP stretch as a critical part of a nuclear localization signal and offer the Rbm20 S637A mouse as a good model for in vivo study

カンゴショク ノ ダイガクイン シンガク ニ カンスル カンゴカンリシャ ノ ニンシキ : -シガケンナイ ノ カンゴカンリシャ ヲ タイショウ トシテ -

背景 近年, 看護系大学院の増加に伴い社会人大学院生が増加している. しかし, 職場の理解が得られず, キャリアを中断して学業に専念する学生や進学そのものを断念する者も多い. 目的 本学が大学院を開設する場合には, 他大学と同様に社会人が入学生の多くを占めると推測されるため, 看護職の大学院進学に関する看護管理者の認識について調査を行なった. 方法 滋賀県内の病院及び実習関連施設等の管理者144名を対象に質問紙調査を実施した. 結果 70名からの回答 (回収率48.61%) が得られた. 大学院修了看護職に期待する管理者は51.42%, 所属施設に大学院卒看護職が必要とする管理者は38.57%であったが, 両者ともわからないと回答した管理者は42.85%であった. また, 進学制度がある施設は25.71%であった. 結論 本調査対象である看護管理者が大学院修了看護職に期待する内容, 必要とする理由は, 研究や教育, 管理的役割, 看護実践の質的向上など先行研究と同様の結果であったが, 大学院修了看護職にどのように活動してもらうかイメージをもてていない管理者も多いことが明らかになった.Background Recently, the number of the graduate students of nursing who also work for full time jobs has been increasing as many new graduate schools of nursing have been established. However, many of them have been had to give up pursuing either their career or education, due to the lack of the understanding from their work places.Object When establishing a graduate school of nursing in our university, it is expected that many of the students will be working full time as it is seen in many other schools. Thus, we conducted a survey to the administrators of nursing institutions asking about their opinions for their workers to go on to graduate school education.Method Surveyed on 144 administrators of nursing institutions in Shiga prefecture, including the hospitals and institutions where our students train in, through questionnaires.Result 70 cases were collected (response rate: 48.61%). 51.42% have positive opinions forward the workers who have finished the master\u27s course of the field, 38.57% said they need them at their work places, and 42.85% said they do not know. However, only 25.71% of the institutions provided the system of supporting the workers for their further education and their main concern seems to be how the organizations and the workers can make mutual understanding for their career.Conclusion The survey showed that some of the administrators have positive opinions toward the workers who have finished the master\u27s degree course of nursing and that they feel the need for them at their work places as it was shown in previous studies. However, it has also been found that many of them do not have a clear picture of how those workers can be actively participated at their work places

コロナ禍のオンライン実習に 360度カメラを導入した効果と課題

　COVID‐19の感染拡大により、オンライン実習においてリアリティを追及した実習が行えるように、実習先施設の映像を360度カメラで撮影し、その映像をVRゴーグルにより視聴する実習を取り入れ、その効果と課題を明らかにすることを目的に、介護福祉養成課程3回生18名にアンケート調査を実施した。その結果、360度カメラによる映像の視聴は実習最終日よりも実習19日目の情報収集の段階で学びが大きい(p < .009)ことが明らかになり、細かい点までの観察が繰り返しでき、介護者・利用者双方からの仮想体験が可能で、学生の気づきに効果があった。一方で、映像酔いや目への負担など、身体的負担につながることも示された。さらに、感情面では実習前から実習後にマイナス感情からプラス感情へと改善（ｐ < .001）が確認できた。今後も、ポストコロナや大災害により突然平穏な日常が奪われる可能性があることを視野に入れ、実習先施設と連携を強化する中でオンラインを活用した実習体験プログラムを構築することが重要である

Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain

In proliferating neural epithelia, cells undergo interkinetic nuclear migration: stereotyped cell cycle-dependent movements in the apico-basal plane. The microtubule-binding protein Tpx2 is here shown to regulate the G2-phase basal-to-apical migration, while passive displacement effects are responsible for basally directed movements

Protection of Macaques with Diverse MHC Genotypes against a Heterologous SIV by Vaccination with a Deglycosylated Live-Attenuated SIV

HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc), following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a successful HIV vaccine against diverse isolates

Geodemographics profiling of influenza A and B virus infections in community neighborhoods in Japan

<p>Abstract</p> <p>Background</p> <p>The spread of influenza viruses in a community are influenced by several factors, but no reports have focused on the relationship between the incidence of influenza and characteristics of small neighborhoods in a community. We aimed to clarify the relationship between the incidence of influenza and neighborhood characteristics using GIS and identified the type of small areas where influenza occurs frequently or infrequently.</p> <p>Methods</p> <p>Of the 19,077 registered influenza cases, we analyzed 11,437 influenza A and 5,193 influenza B cases that were diagnosed by the rapid antigen test in 66-86 medical facilities in Isahaya City, Japan, from 2004 to 2008. We used the commercial geodemographics dataset, Mosaic Japan to categorize and classify each neighborhood. Furthermore, we calculated the index value of influenza in crude and age adjusted rates to evaluate the incidence of influenza by Mosaic segmentation. Additional age structure analysis was performed to geodemographics segmentation to explore the relationship between influenza and family structure.</p> <p>Results</p> <p>The observed number of influenza A and B patients in the neighborhoods where young couples with small children lived was approximately 10-40% higher than the expected number (p < 0.01) during all seasons. On the contrary, the number of patients in the neighborhoods of the aging society in a rural area was 20-50% lower than the expected number (p < 0.01) during all seasons. This tendency was consistent after age adjustment except in the case of influenza B, which lost significance in higher incidence areas, but the overall results indicated high transmission of influenza in areas where young families with children lived.</p> <p>Conclusions</p> <p>Our analysis indicated that the incidence of influenza A and B in neighborhood groups is related to the family structure, especially the presence of children in households. Simple statistical analysis of geodemographics data is an effective method to understand the differences in the incidence of influenza among neighborhood groups, and it provides a valuable basis for community strategies to control influenza.</p

A 2-year follow-up study on falls and related factors among community-dwelling elderly individuals

　Purpose：We conducted a 2-year follow-up study on falls and related causes experienced by localregion, independent elderly citizens．　Method：We analyzed a total of 533 subjects, all independent elderly citizens living in Kameoka City in Kyoto Prefecture who participated in both the 2011 Everyday Life Sphere Needs Assessment and the 2013 Physical Strength Measurements studies． Our study focused on the 25 items included as basic attributes in the 2011 Everyday Life Sphere Needs Assessment．After performing an analysis of the relationships between gender, age, and fall experience, we employed the existence of falls as a subordinate variable, age as a covariant, and each of the 25 basic-attribute items as independent variables in a multivariate logistic regression analysis to grasp the causes related to falls． Furthermore, we used 7 determinate items and a batch-input logistic regression analysis method to analyze the effect of an independent life style on falls．　Results：In the 2-year follow-up study, 35.5% of the subjects experienced at least one fall．The age of the subjects experiencing falls was slightly higher in the female group, compared with the males, but no significant difference was demonstrated．A significant difference was demonstrated in the ratio of falls in the highly-aged elderly group, compared with the lower-aged elderly group． In regard to the relationship between falls and each of the determinate items, in the male group, significant differences were demonstrated for motility, oral functions, memory lapses, and the tendency for depression, and especially the motility function showed a strong causal relationship, even with suppression of the other causes． In the female group, a significant relationship was demonstrated between subjects with a tendency for depression and subjects with a high instrumental activities of daily living index, and with suppression of the other causes in the analysis, a significant relationship was demonstrated between subjects with a low oral function index and a high instrumental activities of daily living index．　Conclusion：It was suggested that even the independent elderly citizens were predisposed to fall down by aging． In addition, sex deference of factor related to falls was observed, and thus sexspecific support policy for fall prevention that considered a characteristic and a background by sex is necessary．　目的：地域在住の自立高齢者を対象に2 年間の追跡調査を行い，転倒経験の有無とその関連要因を分析した。　方法：京都府亀岡市在住の自立高齢者で，2011 年の日常生活圏域ニーズ調査と2013 年の体力測定の両方に参加した533 人について分析した。調査内容は，基本属性の他，日常生活圏域ニーズ調査25項目を用いて，①運動機能，②低栄養，③口腔機能，④閉じこもり，⑤物忘れ，⑥うつ傾向，⑦手段的日常生活動作（IADL）の7 つの判定項目を設定した。分析は，性，年齢と転倒経験との関連を分析した後，転倒有無を従属変数，年齢を共変量，各判定項目それぞれを独立変数とするロジスティック回帰分析により転倒に関連する要因を把握した。また，7 つの判定項目を一括投入するロジスティック回帰分析により転倒への独立した影響を分析した。　結果：追跡2年間において，少なくとも1回以上転倒のあった者は35.5%であった。女性は男性より転倒した者がやや高率であったが有意差はなく，後期高齢者は前期高齢者より有意に高率であった。転倒と各判定項目との関連は，男性では，運動機能，口腔機能，物忘れ，うつ傾向において有意差がみられ，とくに運動機能は，他の要因の影響を調整しても強い関連を示した。女性では，うつ傾向とIADLの高い者に有意な関連がみられ，他の要因の影響を調整した分析では口腔機能の低い者，IADL の高い者に有意な関連がみられた。　考察：地域在住の自立した高齢者であっても，加齢により転倒しやすくなることが示唆された。また，転倒に関連する要因において，男性と女性とで異なった様相を呈し，性による特性や背景を考慮した転倒予防対策が必要であると推察された。原

Arabidopsis HDA6 Regulates Locus-Directed Heterochromatin Silencing in Cooperation with MET1

Heterochromatin silencing is pivotal for genome stability in eukaryotes. In Arabidopsis, a plant-specific mechanism called RNA–directed DNA methylation (RdDM) is involved in heterochromatin silencing. Histone deacetylase HDA6 has been identified as a component of such machineries; however, its endogenous targets and the silencing mechanisms have not been analyzed globally. In this study, we investigated the silencing mechanism mediated by HDA6. Genome-wide transcript profiling revealed that the loci silenced by HDA6 carried sequences corresponding to the RDR2-dependent 24-nt siRNAs, however their transcript levels were mostly unaffected in the rdr2 mutant. Strikingly, we observed significant overlap of genes silenced by HDA6 to those by the CG DNA methyltransferase MET1. Furthermore, regardless of dependence on RdDM pathway, HDA6 deficiency resulted in loss of heterochromatic epigenetic marks and aberrant enrichment for euchromatic marks at HDA6 direct targets, along with ectopic expression of these loci. Acetylation levels increased significantly in the hda6 mutant at all of the lysine residues in the H3 and H4 N-tails, except H4K16. Interestingly, we observed two different CG methylation statuses in the hda6 mutant. CG methylation was sustained in the hda6 mutant at some HDA6 target loci that were surrounded by flanking DNA–methylated regions. In contrast, complete loss of CG methylation occurred in the hda6 mutant at the HDA6 target loci that were isolated from flanking DNA methylation. Regardless of CG methylation status, CHG and CHH methylation were lost and transcriptional derepression occurred in the hda6 mutant. Furthermore, we show that HDA6 binds only to its target loci, not the flanking methylated DNA, indicating the profound target specificity of HDA6. We propose that HDA6 regulates locus-directed heterochromatin silencing in cooperation with MET1, possibly recruiting MET1 to specific loci, thus forming the foundation of silent chromatin structure for subsequent non-CG methylation

A new species of the rare, deep-sea polychaete genus Benthoscolex from the Sea of Kumano, Japan (Annelida, Amphinomidae)

A new species of amphinomid polychaete, Benthoscolex seisuiae sp. n., is described from the Sea of Kumano, Japan, from depths of 487-596 m. The species is distinguishable from its congeners by the following features: i) palps 1.8 times as long as lateral antennae; ii) branchiae do not reach to the tip of the notochaetae. This is the first record of Benthoscolex from Japan. A partial mitochondrial cytochrome c oxidase subunit I gene sequence from the holotype of B. seisuiae sp. n. is provided for reliable species identification in the future