Supervised Sparse Components Analysis with Application to Brain Imaging Data

We propose a dimension-reduction method using supervised (multi-block) sparse (principal) component analysis. The method is first implemented through basis expansion of spatial brain images, and the scores are then reduced through regularized matrix decomposition to produce simultaneous data-driven selections of related brain regions, supervised by univariate composite scores representing linear combinations of covariates. Two advantages of the proposed method are that it identifies the associations between brain regions at the voxel level and that supervision is helpful for interpretation. The proposed method was applied to a study on Alzheimer’s disease (AD) that involved using multimodal whole-brain magnetic resonance imaging (MRI) and positron emission tomography (PET). For illustrative purposes, we demonstrate cases of both single- and multimodal brain imaging and longitudinal measurements

Intramolecular interaction of NEP regulated by CRM1 ensures the unidirectional transport of M1 for the nuclear export of influenza viral ribonucleoprotein

IntroductionThe influenza virus genome consists of single-stranded RNAs and forms viral ribonucleoprotein (RNP) complexes. After viral genome replication in the nucleus, the viral RNP interacts with viral protein M1. The M1-viral RNP complex is exported to the cytoplasm via the CRM1-dependent pathway using NS2/NEP as an export adaptor protein. NEP is a 14 kDa protein and diffusely localizes in the nucleus and cytoplasm. Upon binding to the NLS motif of M1, NEP inhibits the nuclear accumulation of M1 and promotes the nuclear export of M1-viral RNP complex. However, the detail mechanism by which NEP binds to M1 only in the nucleus remains unclear.MethodsTo visualize the interaction of NEP with M1 in the formation of vRNP export complexes, we performed in situ proximity ligation assays. The close proximity of N-terminal and C-terminal domains of NEP was tested by split Renilla luciferase complementation assays in which the N-terminal and C-terminal fragments of Renilla luciferase were fused to the N-terminus and C-terminus of NEP, respectively.Results and discussionWe found that the intramolecular interaction of NEP inhibits the interaction of NEP with M1. The intramolecular interaction of NEP was mediated through the interaction of the N-terminal NES motif with the M1-binding domain at the C-terminus. By adding leptomycin B, a potent inhibitor of CRM1, the interaction of NEP with M1 was impaired. These results suggest that CRM1 disrupts the intramolecular interaction of NEP by recognizing the NES motif at the N-terminus of NEP, thereby promoting the interaction of NEP with M1. We also found that NEP mutant deficient in the intramolecular interaction was co-localized with M1 at the plasma membrane and did not show nuclear localization with M1. Based on these results, we propose that the intramolecular interaction of NEP regulated by CRM1 ensures the unidirectional transport of M1

Extracurricular Club Activity Reform in Japanese Public Junior High Schools: The Case of Takarazuka City

This paper examines the current state of Extracurricular Club Activities (ECAs) in Japan, focusing on the case of ECA reform in the Takarazuka City Board of Education (TCBE) and junior high schools in Takarazuka City. First, we provide an overview of the current status of ECAs in Japan. ECAs originated in the Meiji period (1868-1912) and grew out of the newly established Free Study subject under the post-war education reform. Furthermore, in the modern era of nuclear families and declining birthrates, ECAs have played an essential role as an educational activity that provides students with opportunities to engage in group activities with students of a variety of ages and to develop their communication skills. At the same time, the government has been promoting reform of ECAs with the aim of reducing the burden on teachers under the principles of the ‘school as a team’ and ‘work-style reform’ efforts. Next, we describe ECA reforms that our research group has implemented in cooperation with TCBE. In FY 2020, we conducted a questionnaire survey of students, parents and teachers to ascertain the status of ECAs in Takarazuka City. The results of this survey contributed to supporting the formulation of several education policies. We also recommended measures for ECA reform that TCBE should implement. First, the school board should allow students to commute out of the school district if a secondary school within a designated school zone does not have an ECA of their choice. Second, the school board funding for ECAs in each school should ensure that there are at least two instructors supervising each club. Third, the school board should encourage each school to train junior and senior high school students to become volunteer personnel in ECAs. We need further research into how local education boards and schools could train junior high and high school students for these volunteer roles.departmental bulletin pape

Network-based diagnostic probability estimation from resting-state functional magnetic resonance imaging

Brain functional connectivity is a useful biomarker for diagnosing brain disorders. Connectivity is measured using resting-state functional magnetic resonance imaging (rs-fMRI). Previous studies have used a sequential application of the graphical model for network estimation and machine learning to construct predictive formulas for determining outcomes (e.g., disease or health) from the estimated network. However, the resulting network had limited utility for diagnosis because it was estimated independent of the outcome. In this study, we proposed a regression method with scores from rs-fMRI based on supervised sparse hierarchical components analysis (SSHCA). SSHCA has a hierarchical structure that consists of a network model (block scores at the individual level) and a scoring model (super scores at the population level). A regression model, such as the multiple logistic regression model with super scores as the predictor, was used to estimate diagnostic probabilities. An advantage of the proposed method was that the outcome-related (supervised) network connections and multiple scores corresponding to the sub-network estimation were helpful for interpreting the results. Our results in the simulation study and application to real data show that it is possible to predict diseases with high accuracy using the constructed model

Influenza A Virus NS1 Protein Suppresses JNK1-Dependent Autophagosome Formation Mediated by Rab11a Recycling Endosomes

Autophagy is an essential process for cellular metabolism and homeostasis, but also functions as one of innate immune responses against pathogen infection. However, in contrast to cellular metabolism and homeostasis pathways, less is known about how virus infection leads to autophagosome formation. Here, we showed that influenza A virus NS1 protein inhibits the formation of autophagosomes. The autophagosome formation was induced by infection with NS1 mutant virus lacking the dsRNA-binding activity for inhibition of innate immune responses (R38AK41A) or the activation of PI3K-Akt signaling pathway (Y89F). R38AK41A mutant infection induced phosphorylation of JNK1 and up-regulated the expression of autophagy-related genes which are downstream of JNK1 signaling pathway. We also found that the amount of phosphorylated TSC2, which activates mTOR, increased in wild type-infected cells but not in Y89F mutant-infected cells. These findings suggest that NS1 inhibits the autophagosome formation through both the inhibition of JNK1 and the activation of PI3K-Akt-mTOR pathway. Further, viral ribonucleoprotein (vRNP) complexes were selectively sequestered into autophagosomes, and knockdown of Rab11a, which is responsible for the apical transport of vRNP complexes, impaired not only engulfment of vRNP complexes by autophagosomes but also the formation of autophagosomes in R38AK41A mutant-infected cells. This indicates that Rab11a-positive recycling endosomes function as a donor membrane for the phagophore elongation and an autophagic receptor for the selective engulfment of viral RNP complexes. Based on these results, we propose that NS1 inhibits JNK1-mediated autophagy induction and the sequestration of vRNP complexes into autophagosomes

A Survey on Cooperation among Day Care Centers, Preschools, and Elementary Schools of Special Needs Classroom Teachers in Elementary Schools: Compared with Five Years Old Children Teachers and First Grade Teachers

本研究では，X市の保育所・幼稚園の年長担任，小学校の１年担任と特別支援学級担任を対象とした保幼小連携の実態調査を行った。その結果，特別支援学級担任は１年担任よりも保幼小連携の際に活用するツールが必要だと認識していた。さらに，保幼小連携において今後最も必要なことは，「気になる子どもの様子について情報交換する機会」であった。このことから，特別支援学級担任は保護者の願いを含む，個別の情報については詳しい引継ぎが必要だと捉えている。一方で，保幼小連携において現在実施していることについては，３者とも最も高い割合で「就学前に実施される連絡会」が挙げられていた。The purpose of this study was to explain cooperation between day care centers teachers, preschools teachers and elementary schools teachers of five years old children teachers, first grade teachers and teachers of special needs classrooms in elementary schools in the X city. In the result, teachers of special needs classrooms in elementary schools recognized the need to use the tool when they cooperate between day care centers and preschools. And, the most important thing about cooperation among day care centers, preschools, and elementary schools was “the opportunity to share information on children with special needs.” From this, they think that transition to elementary schools needs more individualized information including parents’ wishes. On another front, five years old children teachers, first grade teachers, and teachers of special needs classrooms in elementary schools conduct“ conference before school age” at the highest rate