Gan-Lu-Yin (Kanroin), Traditional Chinese Herbal Extracts, Reduces Osteoclast Differentiation In Vitro and Prevents Alveolar Bone Resorption in Rat Experimental Periodontitis

Gan-Lu-Yin (GLY), a traditional Chinese herbal medicine, shows therapeutic effects on periodontitis, but that mechanism is not well known. This study aims to clarify the precise mechanism by investigating the inhibitory effects of GLY extracts on osteoclastogenesis in vitro and on bone resorption in periodontitis in vivo. RAW264.7 cells are cultured with soluble receptor activator of nuclear factor-kappa B (sRANKL) and GLY extracts (0.01–1.0 mg/mL), and stained for tartrate-resistant acid phosphatase (TRAP) to evaluate osteoclast differentiation. Experimental periodontitis is induced by placing a nylon ligature around the second maxillary molar in rats, and rats are administered GLY extracts (60 mg/kg) daily for 20 days. Their maxillae are collected on day 4 and 20, and the levels of alveolar bone resorption and osteoclast differentiation are estimated using micro-computed tomography (CT) and histological analysis, respectively. In RAW264.7 cells, GLY extracts significantly inhibit sRANKL-induced osteoclast differentiation at a concentration of more than 0.05 mg/mL. In experimental periodontitis, administering GLY extracts significantly decreases the number of TRAP-positive osteoclasts in the alveolar bone on day 4, and significantly inhibits the ligature-induced bone resorption on day 20. These results show that GLY extracts suppress bone resorption by inhibiting osteoclast differentiation in experimental periodontitis, suggesting that GLY extracts are potentially useful for oral care in periodontitis

A survey of problems in the care and support of infants born at very low birth weight

Orientador: Prof. Dr. Clodomiro Unsihuay-VilaCoorientadora: Prof.a Dr. a Thelma Solange P. FernandesDissertação (mestrado) - Universidade Federal do Paraná, Setor de Tecnologia, Programa de Pós-Graduação em Engenharia Elétrica. Defesa : Curitiba, 29/08/2019Inclui referências: p. 127-133Área de concentração: Sistema de energiaResumo: A frota de veículo elétrico (VE) cresce rapidamente no mundo, em 2018 já superou a marca de 5,1 milhões. A inserção de VE nas redes ativas de distribuição significa uma evolução nos sistemas de energia elétrica, mas essa evolução requer avanços no planejamento da operação, de maneira a considerar o aumento da complexidade que esses novos elementos podem causar na rede. Por isso, se faz necessário ferramentas computacionais que permitam analisar os impactos que o VE causa na operação de redes ativas de distribuição, de maneira a auxiliar na definição de estratégias operativas apropriadas e garantir a otimização de todos os recursos energéticos do sistema. Dessa forma, nesta dissertação foi desenvolvido um modelo computacional, formulado como um problema de otimização capaz de determinar a programação diária da operação de redes ativas de distribuição, considerando a inserção do VE na rede. O problema foi abordado através de um Fluxo de Potência Ótimo (FPO) multiperíodo. A intertemporalidade do problema é formulada através da introdução de uma função de acoplamento representada pela energia armazenada pelas baterias do VE. A resolução do FPO foi através do Métodos dos Pontos Interiores versão Primal-Dual. O horizonte de planejamento é de 24 períodos, divididos em horas. Também é considerado a geração distribuída fotovoltaica e um sistema de tarifação horária de energia. O veículo elétrico é incorporado no problema por meio da adição de uma variável de otimização à função objetivo que além de alterar as restrições de balanço de potência também é usada para monitorar a energia armazenada nas baterias. Como resultado, têm-se um FPO multiperíodo que busca, além da minimização dos custos operativos e perdas de transmissão, também a maximização da energia armazenada nas baterias dos veículos elétricos conectados à rede visando a injeção ótima de energia à rede ativa. Nas simulações realizadas, foram utilizados cenários determinísticos de conexão do VE para avaliar seus impactos nas perdas, custos operacionais e perfil de tensão do sistema elétrico. Os resultados de simulações demonstraram que, no cenário de perfil residencial, que possibilitam o carregamento/descarregamento, é perceptível uma melhora no perfil de tensão do sistema. Isso mostra que a apropriada operação dos VEs com possibilidade de injeção de energia à rede podem ser uma boa alternativa para deslocar picos de carga e reduzir custos operacionais da rede ativa de distribuição. Para o perfil comercial, é perceptível uma redução do perfil de tensão para o seu instante de conexão. Entretanto, esse comportamento pode ser complementado através de uma geração fotovoltaica, que apresenta seus picos de geração nos mesmos instantes em que o VE carrega. Para os cenários que consideram uma alta inserção de VE na rede, os impactos no perfil de tensão do sistema são bastante significativos, demonstrando que para que a rede seja capaz de atender uma grande frota de VEs devem ser feitos investimentos na infraestrutura da rede de distribuição. O impacto da inserção do VE à rede pode aumentar em até 40% as perdas do sistema. Os impactos no custo de operação são significativos, podendo aumentar em até 19%, para cenários de alta penetração de VE. Palavras-chave: Planejamento da Operação. Redes Ativas de Distribuição. Veículo Elétrico. Fluxo de Potência Ótimo. Método dos Pontos Interiores versão Primal-Dual. Armazenamento de energia em baterias.Abstract: The electric vehicle (EV) fleet is growing rapidly in the world, by 2018, it has already surpassed the 5.1 million mark. The insertion of EV into active distribution grids means an evolution in power systems, but this evolution requires advances in operation planning in order to consider the increased complexity that these new elements in the grid may cause. Therefore, computational tools are needed to analyze the impacts that EV has on the operation of active distribution networks, in order to help define appropriate operating strategies and ensuring the optimization of all energy resources in the system. Thus, in this dissertation a computational model was developed, formulated as an optimization problem capable of determining the daily programming of the active distribution networks operation, considering the insertion of the EV in the network. The problem was addressed through a Multi-Period Optimal Power Flow (OPF). The intertemporality of the problem is formulated by introducing a coupling function represented by the energy stored by LV batteries. The resolution of the OPF was through the Primal-Dual Interior Point Method. The planning horizon is 24 periods, divided into hours, under the influence of photovoltaic generation and an hourly energy hourly charging system. The electric vehicle is incorporated into the problem by adding an optimization variable to the objective function which in addition to changing the power balance restrictions is also used to monitor the energy stored in the batteries. As a result, there is a MultiPeriod OPF that seeks, in addition to minimizing operating costs and transmission losses, also maximizing the energy stored in the batteries of electric vehicles connected to the grid for optimal injection of power to the grid at peak hours. In the simulations performed, deterministic EV connection scenarios were used to assess their impacts on losses, operating costs and voltage profile. Simulation results showed that, in the residential profile scenario, which enables loading / unloading, an improvement in the system voltage profile is noticeable. Showing that appropriate EV operation can be a good alternative for shifting power generation from light load moments of the system to high load moments, optimizing the use of system energy resources, reducing operating costs of active distribution. For the commercial profile, a reduction of the voltage profile is noticeable for its connection time. However, this behavior can be complemented by a photovoltaic generation, which presents its generation peaks at the same time that the EV charges. For scenarios that consider a high insertion of EV in the grid, the impacts on the system voltage profile are quite significant, demonstrating that for the grid to be able to serve a large fleet of EVs, investments in the distribution network infrastructure must be made. The impacts of EV insertion into the network can increase system losses by up to 40%. The impacts on operating costs are significant and may increase by up to 19% for high EV penetration scenarios. Keywords: Operation Planning. Active Distribution Networks. Electric Vehicle. Optimal Power Flow. Primal-Dual Interior Point Method. Energy storage in batteries

Purification, crystallization and preliminary X-ray analysis of a deletion mutant of a major buckwheat allergen

A 16 kDa buckwheat protein (BWp16) is a major allergen responsible for immediate hypersensitivity reactions including anaphylaxis. An immunologically active mutant of BWp16 was prepared and a three-wavelength MAD data set was collected from a crystal of selenomethionine-labelled mutant protein

大都市団地居住高齢者の社会関係と生活ニーズ充足のためのソーシャルサポート ─ライフコースとケアリング関係の視点からの分析─

本研究の目的は,ライフコースとケアリング関係の視点から,大都市団地居住高齢者の社会関係と生活ニーズ充足のためのソーシャルサポートとの関連を分析し,地域包括ケアの課題を検討することである。東京都A 市B 団地居住高齢者429 名への訪問調査を2011 年5-6 月に実施した(有効N=196 名,有効回答率:46.0%)。主な結果として,1)生活ニーズのある人(全体の1 割弱)の2-4 割に支援者がおらず,有支援者の2 割弱が家事,買い物,ゴミだし,当番の場合に近所の人を担い手としてあげた(複数回答),2)困りごとの相談相手がいない人は2 割弱で,男性の方が女性よりいない割合が高い,3)ロジスティック回帰分析の結果,独居,男性,近隣ネットワークが小さい方が相談者がいない確率が高いことがわかった。独居や男性など既存の社会ネットワークを活用したソーシャルサポートの活用可能性が乏しいグループには適切な支援策が必要であることが示唆された。小規模調査の限界もあるが,団地居住高齢者の多様な社会関係とソーシャルサポートの現状をふまえての地域包括ケアの課題があきらかになった。The purpose of this study is two-fold: 1) to examine the association between social relationships and support for meeting the daily life needs of elderly people in an urban housing complex from the lifecourse and caring-relations perspectives and 2) to discuss the challenges of community comprehensive care. Structured home-visit interviews were conducted among 429 elderly people at Housing Complex B in City A, in the Tokyo Metropolitan area, from May to June, 2011. Valid responses were obtained from 196 persons, for a response rate of 46.0%. The results are as follows: 1) among the elderly who had daily-life needs (less than ten percent of total respondents), twenty percent relied on neighbors for doing housework, shopping, taking out garbage, and performing duties in the housing complex (multiple answer); 2) less than twenty percent of respondents had no one they could turn to for advice regarding their day-to-day difficulties; and 3) as a result of logistic regression analysis, single people, males, and respondents with small networks of neighbors were found to be less likely than couples, females, and those with large networks of neighbors to have anyone to turn to for advice. Our findings indicate thatit is necessary to have an appropriate support system for those who have limited support available in their existing social network (e.g. single people, males). In spite of the limitation of a small sample, we could clarify some of the challenges for community comprehensive care for elderly people by considering the diverse social relations and social support available to them in a housing complex

Cilostazol attenuates ischemia?reperfusion-induced blood?brain barrier dysfunction enhanced by advanced glycation endproducts via transforming growth factor-β1 signaling

We investigated the effects of cilostazol, a selective inhibitor of phosphodiesterase 3, on blood-brain barrier (BBB) integrity against ischemia-reperfusion injury enhanced by advanced glycation endproducts (AGEs). We used in vitro BBB models with primarily cultured BBB-related cells from rats (brain capillary endothelial cells, astrocytes and pericytes), and subjected cells to either normoxia or 3-h oxygen glucose deprivation (OGD)/24-h reoxygenation with or without AGEs. Treatment of AGEs did not affect the transendothelial electrical resistance (TEER) in the BBB model under normoxia, but there was a significant decrease in TEER under 3-h OGD/24-h reoxygenation conditions with AGEs. Cilostazol inhibited decreases in TEER induced by 3-h OGD/24-h reoxygenation with AGEs. Immunocytochemical and Western blot analyses showed that AGEs reduced the expression of claudin-5, the main functional protein of tight junctions (TJs). In contrast, cilostazol increased the expression of claudin-5 under 3-h OGD/24-h reoxygenation with AGEs. Furthermore, while AGEs increased the production of extracellular transforming growth factor (TGF)-β1, cilostazol inhibited the production of extracellular TGF-β1 and restored the integrity of TJs. Thus, we found that AGEs enhanced ischemia-reperfusion injury, which mainly included decreases in the expression of proteins comprising TJs through the production of TGF-β1. Cilostazol appeared to limit ischemia-reperfusion injury with AGEs by improving the TJ proteins and inhibiting TGF-β1 signaling

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target