酢酸摂取と運動が脂肪代謝と運動耐久性に及ぼす影響

Previously, we found that acetic acid had effects on lipid metabolism in skeletal muscles and has functions that work against obesity and obesity-linked type 2 diabetes through the activation of AMPactivated protein kinase (AMPK). During exercise, AMPK is activated in skeletal muscle according to exercise intensity and it increases fatty acid oxidation. The purpose of this study was to investigate the interactive effects of chronic intake of acetic acid and exercise training on lipid metabolism and endurance performance. Six-week-old SD rats were randomly assigned to four groups: water-injected (rest-water), acetic acid-injected (rest-ace), exercise-trained after injection of water (water-ex), and exercise-trained after injection of acetic acid (ace-ex) for 4 weeks. Body weight (BW) in rest-ace and ace-ex groups was significantly lower than rest-water group. Exercise-training groups showed an increase of exercise capacity, by the addition of intake of acetic acid, lipid oxidation was promoted during exercise tolerance test. Skeletal muscle of rats treated with acetic acid and exercise training led to higher expressions of cytochrome c (cycs), and tended to stimulate expressions of peroxisome proliferator-activated receptor coactivator 1-α (PGC1-α ) and MHC1 genes than those of rest-water group. Those results indicate that treatments both of exercise training and intake of acetic acid contribute to enhancement of lipid metabolism and improvement of exercise capacity.これまで我々は、酢酸の摂取が骨格筋内のAMP活性化プロテインキナーゼ（AMPK）の活性化を介して脂質代謝と肥満、肥満に関連した2型糖尿病の予防に効果があることを示唆してきた。AMPKは運動によって骨格筋で活性化し、脂肪酸酸化を促進する。この研究は、4週間の継続的な酢酸摂取と運動トレーニングが運動中の脂肪代謝と運動耐久性に及ぼす影響について調べることを目的とした。　6週齢のSD系雄ラットを安静期に水を摂取するrest-water群、酢酸を摂取するrest-ace群、運動前に水を摂取するwater-ex群、運動前に酢酸を摂取するace-ex群に無作為に分け実験を行った。酢酸を継続的に摂取すると水摂取に比較して腹腔内脂肪量の減少と体重増加の抑制がみられた。また継続的な酢酸摂取および運動トレーニングにより、耐久性運動下でのグルコース利用の抑制および脂肪酸酸化の促進が見られた。酢酸摂取および運動トレーニング群の腓腹筋では、MHCIおよびcytochrome c等の遅筋線維マーカー遺伝子が増加していた。継続的な酢酸摂取と運動トレーニングにより、脂肪代謝と運動耐久性の向上が示唆された

Virtual reality perceptual training can improve the temporal discrimination ability of swinging during softball batting

Perception and action uncoupling in fastball sports anticipatory training is often criticized. Nevertheless, perception-only training offers distinct advantages, such as flexibility concerning time, place, and injury limitations. Therefore, the effectiveness of this training approach warrants evaluation. This study developed a virtual reality (VR) training system based on the idea that the two visual pathways in the brain are associated with visual information attributes, rather than perception or action. A key feature of this study's perception-only training was its presentation of not only the opponent's kinematics but also the ball's flight information (the attributes that guide hitting) to train the visual system necessary for real situations. Seventeen female softball batters were assigned to two groups: a training group (N = 9) and a control group (N = 8). Only the training group underwent the VR anticipatory skill training to discriminate the different ball speeds. Both groups completed a perception test and an action test on the VR during the pre- and post-training periods. The perception test assessed response accuracy (RA) in discriminating ball speed, and the action test assessed the temporal difference in swing onset (delta onset). Comparison of these two outcome variables between groups revealed that perception-only training improved both perceptual and action responses. This study demonstrated the effectiveness of perception-only training and emphasized the need for its thoughtful utilization and design

Oncofertility care in young women and the outcomes of pregnancy over the last 5 years

Aim: To ascertain the actual outcomes of oncofertility care in young women to provide more appropriate care. Materials & methods: We analyzed the data of 67 female patients under 43 years of age who underwent oncofertility care between January 2015 and September 2019. Results: There were 28 patients with breast cancer, 19 patients with hematologic cancer and 20 patients with other cancer diagnoses. Breast cancer patients tended to take longer than hematologic cancer patients to initiate oncofertility treatment. Despite undergoing oncofertility care, seven of nine pregnant patients did not choose assisted reproductive technology (ART). Conclusion: As spontaneous pregnancies were more common than ART pregnancies in our study, pregnancy by not only ART but also non-ART method is a viable option for young cancer survivors

Економіко-математичне моделювання оптимізації фінансування заходів щодо збереження біорізноманіття (Economic modeling optimization funding for biodiversity)

Удосконалено організаційно-економічний механізм збереження біорізноманіття України відповідно до умов збалансованого розвитку. Обґрунтовано концептуальні положення збереження біорізноманіття, які базуються на соціо-еколого-економічній оцінці функціонування екосистем. Розроблено методологічні підходи до врахування збереження біорізноманіття у національних рахунках держави, що ґрунтуються на визначенні економічної оцінки функціонування природних екосистем. Поглиблено методологію збереження біорізноманіття на основі поєднання і розвитку теорії систем та інституціональної економіки. Розширено механізми застосування інноваційних інструментів збереження біорізноманіття. Розроблено концептуальні підходи маркетингової стратегії розвитку природно-заповідних територій на основі формування їх позитивного іміджу й адаптації до ринкових умов. (The investigation is devoted to the organization-economic mechanism improvement of the biodiversity conservation in Ukraine in relation to the sustainable development conditions. The conceptual principles of the biodiversity that are based on ecological and social and economic assessment of ecosystem functioning were scientifically proved for the first time in this research. The methodological approaches to the biodiversity conservation in the national state accounts were developed and they are based on the new calculations of the economic evaluation of the natural ecosystem functioning. The methodology and tools of the economic mechanism for resolving environmental conflicts at international level are improved. The methodology of the biodiversity conservation which is based on the institutional economics theory and the systems theory was improved. The innovative mechanisms for biodiversity conservation tools were expanded.

Prediction of stroke patients’ bedroom-stay duration: machine-learning approach using wearable sensor data

Background: The importance of being physically active and avoiding staying in bed has been recognized in stroke rehabilitation. However, studies have pointed out that stroke patients admitted to rehabilitation units often spend most of their day immobile and inactive, with limited opportunities for activity outside their bedrooms. To address this issue, it is necessary to record the duration of stroke patients staying in their bedrooms, but it is impractical for medical providers to do this manually during their daily work of providing care. Although an automated approach using wearable devices and access points is more practical, implementing these access points into medical facilities is costly. However, when combined with machine learning, predicting the duration of stroke patients staying in their bedrooms is possible with reduced cost. We assessed using machine learning to estimate bedroom-stay duration using activity data recorded with wearable devices.Method: We recruited 99 stroke hemiparesis inpatients and conducted 343 measurements. Data on electrocardiograms and chest acceleration were measured using a wearable device, and the location name of the access point that detected the signal of the device was recorded. We first investigated the correlation between bedroom-stay duration measured from the access point as the objective variable and activity data measured with a wearable device and demographic information as explanatory variables. To evaluate the duration predictability, we then compared machine-learning models commonly used in medical studies.Results: We conducted 228 measurements that surpassed a 90% data-acquisition rate using Bluetooth Low Energy. Among the explanatory variables, the period spent reclining and sitting/standing were correlated with bedroom-stay duration (Spearman’s rank correlation coefficient (R) of 0.56 and −0.52, p < 0.001). Interestingly, the sum of the motor and cognitive categories of the functional independence measure, clinical indicators of the abilities of stroke patients, lacked correlation. The correlation between the actual bedroom-stay duration and predicted one using machine-learning models resulted in an R of 0.72 and p < 0.001, suggesting the possibility of predicting bedroom-stay duration from activity data and demographics.Conclusion: Wearable devices, coupled with machine learning, can predict the duration of patients staying in their bedrooms. Once trained, the machine-learning model can predict without continuously tracking the actual location, enabling more cost-effective and privacy-centric future measurements

Phosphorylation of serine 225 in hepatitis C virus NS5A regulates protein-protein interactions.

Hepatitis C virus (HCV) non-structural protein 5A (NS5A) is a phosphoprotein that plays key, yet poorly defined, roles in both virus genome replication and virion assembly/release. It has been proposed that differential phosphorylation could act as a switch to regulate the various functions of NS5A, however the mechanistic details of the role of this post-translational modification in the virus life cycle remains obscure. We previously reported (Ross-Thriepland et al, 2015) a role for phosphorylation at serine 225 (S225) of NS5A in the regulation of JFH-1 (genotype 2a) genome replication. A phosphoablatant (S225A) mutation resulted in a 10-fold reduction in replication and a perinuclear restricted distribution of NS5A, whereas the corresponding phosphomimetic mutation (S225D) had no phenotype. To determine the molecular mechanisms underpinning this phenotype we conducted a label-free proteomics approach to identify cellular NS5A interaction partners. This analysis 30 revealed that the S225A mutation disrupted the interactions of NS5A with a number of cellular proteins, in particular the nucleosome assembly protein 1-like protein 1 (NAP1L1), bridging integrator 1 (Bin1, also known as Amphiphysin II) and vesicle associated membrane protein-associated protein A (VAP-A). These interactions were validated by immunoprecipitation/western blotting, immunofluorescence and proximity ligation assay. Importantly, siRNA-mediated knockdown of NAP1L1, Bin1 or VAP-A impaired viral genome replication and recapitulated the perinuclear redistribution of NS5A seen in the S225A mutant. These results demonstrate that S225 phosphorylation regulates the interactions of NS5A with a defined subset of cellular proteins. Furthermore, these interactions regulate both HCV genome replication and the subcellular localisation of replication complexes. IMPORTANCE Hepatitis C virus is an important human pathogen. The viral nonstructural 5A protein (NS5A) is the target for new antiviral drugs. NS5A has multiple functions during the virus life cycle, but the biochemical details of these roles remain obscure. NS5A is known to be phosphorylated by cellular protein kinases, and in this study, we set out to determine whether this modification is required for the binding of NS5A to other cellular proteins. We identified 3 such proteins and show that they interacted only with NS5A that was phosphorylated on a specific residue. Furthermore, these proteins were required for efficient virus replication and the ability of NS5A to spread throughout the cytoplasm of the cell. Our results help to define the function of NS5A and may contribute to an understanding of the mode of action of the highly potent antiviral drugs that are targeted to NS5A

Generation of Germline-Competent Rat Induced Pluripotent Stem Cells

Recent progress in rat pluripotent stem cell technology has been remarkable. Particularly salient is the demonstration that embryonic stem cells (ESCs) in the rat (rESCs) can contribute to germline transmission, permitting generation of gene-modified rats as is now done using mouse ESCs (mESCs) or mouse induced pluripotent stem cells (iPSCs; miPSCs). However, determinations of whether rat iPSCs (riPSCs) can contribute to germ cells are not published. Here we report the germline competency of riPSCs.We generated riPSCs by transducing three mouse reprogramming factors (Oct3/4, Klf4, and Sox2) into rat somatic cells, followed by culture in the presence of exogenous rat leukemia inhibitory factor (rLIF) and small molecules that specifically inhibit GSK3, MEK, and FGF receptor tyrosine kinases. We found that, like rESCs, our riPSCs can contribute to germline transmission. Furthermore we found, by immunostaining of testis from mouse-rat interspecific chimeras with antibody against mouse vasa homolog, that riPSCs can contribute to embryonic development with chimera formation in mice (rat-mouse interspecific chimeras) and to interspecific germlines.Our data clearly demonstrate that using only three reprogramming factors (Oct3/4, Klf4, and Sox2) rat somatic cells can be reprogrammed into a ground state. Our generated riPSCs exhibited germline transmission in either rat-rat intraspecific or mouse-rat interspecific chimeras

Japan Prosthodontic Society position paper on “occlusal discomfort syndrome”

Purpose: Dentists may encounter patients who present with a sense of a malocclusion but in whom no objective findings can be detected. For the patient who insists that there is occlusal discomfort, in the absence of evidence some dentists elect to perform an occlusal adjustment that not only fails to alleviate symptoms, and may, in fact, exacerbate the discomfort. The patient–dentist relationship is then likely compromised because of a lack of trust. Study selection: In 2011, the Clinical Practice Guidelines Committee of the Japan Prosthodontic Society formulated guidelines for the management of occlusal discomfort. When formulating clinical practice guidelines, the committee bases their recommendations on information derived from scientific evidence. For ‘‘occlusal dysesthesia,’’ however, there are an insufficient number of high-quality papers related to the subject. Therefore, a consensus meeting was convened by the Japan Prosthodontic Society to examine evidence in the Japanese- and English-language literature and generate a multi-center survey to create an appropriate appellation for this condition. Results: As a result of the consensus meeting and survey findings, this condition may be justifiably termed ‘‘occlusal discomfort syndrome.’’ Conclusions: The Japan Prosthodontics Society believes that identification of an umbrella term for occlusal discomfort might serve as a useful guide to formulating clinical practice guidelines in the future. This position paper represents summary findings in the literature combined with the results of a multicenter survey focused on dental occlusal treatment and the condition of patients who present with occlusal discomfort syndrome

The 2nd DBCLS BioHackathon: interoperable bioinformatics Web services for integrated applications

<p>Abstract</p> <p>Background</p> <p>The interaction between biological researchers and the bioinformatics tools they use is still hampered by incomplete interoperability between such tools. To ensure interoperability initiatives are effectively deployed, end-user applications need to be aware of, and support, best practices and standards. Here, we report on an initiative in which software developers and genome biologists came together to explore and raise awareness of these issues: BioHackathon 2009.</p> <p>Results</p> <p>Developers in attendance came from diverse backgrounds, with experts in Web services, workflow tools, text mining and visualization. Genome biologists provided expertise and exemplar data from the domains of sequence and pathway analysis and glyco-informatics. One goal of the meeting was to evaluate the ability to address real world use cases in these domains using the tools that the developers represented. This resulted in i) a workflow to annotate 100,000 sequences from an invertebrate species; ii) an integrated system for analysis of the transcription factor binding sites (TFBSs) enriched based on differential gene expression data obtained from a microarray experiment; iii) a workflow to enumerate putative physical protein interactions among enzymes in a metabolic pathway using protein structure data; iv) a workflow to analyze glyco-gene-related diseases by searching for human homologs of glyco-genes in other species, such as fruit flies, and retrieving their phenotype-annotated SNPs.</p> <p>Conclusions</p> <p>Beyond deriving prototype solutions for each use-case, a second major purpose of the BioHackathon was to highlight areas of insufficiency. We discuss the issues raised by our exploration of the problem/solution space, concluding that there are still problems with the way Web services are modeled and annotated, including: i) the absence of several useful data or analysis functions in the Web service "space"; ii) the lack of documentation of methods; iii) lack of compliance with the SOAP/WSDL specification among and between various programming-language libraries; and iv) incompatibility between various bioinformatics data formats. Although it was still difficult to solve real world problems posed to the developers by the biological researchers in attendance because of these problems, we note the promise of addressing these issues within a semantic framework.</p

Clinical and molecular features of 66 patients with musculocontractural Ehlers-Danlos syndrome caused by pathogenic variants in CHST14 (mcEDS-CHST14)

Background Musculocontractural Ehlers-Danlos syndrome is caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE). Although 48 patients in 33 families with mcEDS-CHST14 have been reported, the spectrum of pathogenic variants, accurate prevalence of various manifestations and detailed natural history have not been systematically investigated. Methods We collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS-CHST14 through international collaborations. Results Sixty-six patients in 48 families (33 males/females; 0-59 years), including 18 newly reported patients, were evaluated. Japanese was the predominant ethnicity (27 families), associated with three recurrent variants. No apparent genotype-phenotype correlation was noted. Specific craniofacial (large fontanelle with delayed closure, downslanting palpebral fissures and hypertelorism), skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation), cutaneous (hyperextensibility, fine/acrogeria-like/wrinkling palmar creases and bruisability) and ocular (refractive errors) features were observed in most patients (>90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>80%). Median ages at the initial episode of dislocation or large subcutaneous haematoma were both 6 years. Nine patients died; their median age was 12 years. Several features, including joint and skin characteristics (hypermobility/extensibility and fragility), were significantly more frequent in patients with mcEDS-CHST14 than in eight reported patients with mcEDS-DSE. Conclusion This first international collaborative study of mcEDS-CHST14 demonstrated that the subtype represents a multisystem disorder with unique set of clinical phenotypes consisting of multiple malformations and progressive fragility-related manifestations; these require lifelong, multidisciplinary healthcare approaches.Genetics of disease, diagnosis and treatmen