803 research outputs found

    Cardiac PPARα Protein Expression is Constant as Alternate Nuclear Receptors and PGC-1 Coordinately Increase During the Postnatal Metabolic Transition

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    Gene expression data obtained in mouse heart indicate that increased expression for the nuclear receptor, peroxisomal proliferator activated receptor α (PPARα), prompts the postnatal transition from predominantly carbohydrate to fatty acid oxidation preference. However, no phenotypic or proteomic data are available to confirm downstream signaling and metabolic transition in mice. We studied the hypothesis that shifts in nuclear receptor expression trigger the newborn metabolic switch in a newborn sheep. This species is well characterized with regards to developmental changes in substrate oxidative metabolism. Heart tissues from fetal (130 days gestation), newborn ≤24 hours, and 30-day old lambs were evaluated for protein expression from multiple enzymes controlling oxidative metabolism as well as principal nuclear receptors and coactivators. Although muscle and liver type carnitine palmitoyl transferases I showed no significant changes to correspond to the metabolic transition, hexokinase II protein content showed a profound transient drop, and pyruvate dehydrogenase kinase steadily increased. PPARα showed no increases preceding or during the transition, while peroxisomal proliferator activated receptor gamma coactivator-1 (PGC-1) increased approximately 20-fold transiently in newborn heart in conjunction with significant increases in thyroid hormone receptor α1 and retinoid-activated receptor α. These data challenge the paradigm that increases in PPARα prompt the postnatal metabolic switch, and suggest that other nuclear receptors play a major role. As thyroid hormone (TH) modulates PGC-1 expression in sheep during development, these data further suggest that well-characterized perinatal TH surge in sheep contributes to this metabolic switch

    Phylogenomic reappraisal of the family Rhizobiaceae at the genus and species levels, including the description of Ectorhizobium quercum gen. nov., sp. nov.

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    The family Rhizobiaceae contains 19 validly described genera including the rhizobia groups, many of which are important nitrogen-fixing bacteria. Early classification of Rhizobiaceae relied heavily on the poorly resolved 16S rRNA genes and resulted in several taxonomic conflicts. Although several recent studies illustrated the taxonomic status of many members in the family Rhizobiaceae, several para- and polyphyletic genera still needed to be elucidated. The rapidly increasing number of genomes in Rhizobiaceae has allowed for a revision of the taxonomic identities of members in Rhizobiaceae. In this study, we performed analyses of genome-based phylogeny and phylogenomic metrics to review the relationships of 155-type strains within the family Rhizobiaceae. The UBCG and concatenated protein phylogenetic trees, constructed based on 92 core genes and concatenated alignment of 170 single-copy orthologous proteins, demonstrated that the taxonomic inconsistencies should be assigned to eight novel genera, and 22 species should be recombined. All these reclassifications were also confirmed by pairwise cpAAI values, which separated genera within the family Rhizobiaceae with a demarcation threshold of ~86%. In addition, along with the phenotypic and chemotaxonomic analyses, a novel strain BDR2-2T belonging to a novel genus of the family Rhizobiaceae was also confirmed, for which the name Ectorhizobium quercum gen. nov., sp. nov. was proposed. The type strain is BDR2-2T (=CFCC 16492T = LMG 31717T)

    Factors influencing the quality of clinical trials on traditional Chinese medicine— Qualitative interviews with trial auditors, clinicians and academic researchers

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    Background: As clinical trials evaluating the efficacy of traditional Chinese medicine (TCM) therapies have increased, several empirical studies have shown that the quality of TCM trials are generally low in terms of risk of bias. This qualitative study aimed to investigate the factors influencing the quality of TCM clinical trials to provide strategic advice on trial quality improvement. Methods: One focus group with clinical trial auditors (n=4) and six indepth semi-structured interviews with clinical research organization managers (n=2), lecturers and researchers in TCM academic institutions (n=2), a chief physician in a TCM oncology department and a PhD candidate specialized in non-pharmaceutical TCM interventions were conducted. The interviews were audio-recorded, transcribed verbatim and thematically analyzed. Results: Factors that influenced the quality of TCM clinical trials merged on the following 6 themes: trial design; trialists/ participants; trial conducting; TCM specified problems; trial monitoring, and finally societal influences. The lack of expertise and time inputs of the trialists were repeatedly mentioned. Methodological difficulties experienced when conducting TCM trials included calculating sample size, analyzing the efficacy of TCM decoctions with multiple ingredients, blinding in trials investigating non-pharmaceutical TCM interventions were highlighted. Interviewees agreed that third-party monitoring can help improving trial quality and improved participant welfare and may accelerate recruiting processes and increase compliance; however more comprehensive regulations and funding requirements would be needed. Conclusions: This study identified real-life issues influencing the quality of TCM clinical trials from design to reporting. In addition to mandatory training for TCM trial designers and coordinators, more effective institutional oversight is required. Future studies should explore specific measures to address the methodological problems in TCM trials and explore how the quality of TCM trials can affect further evidence synthesis and clinical practice

    Research on Definition of Short-Circuit Region for Γ-source Circuit Breaker

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    This article proposes a method defining area of short-circuit and load step change for Γ-source circuit breaker through deriving the law between the variables of transformation ratio, coupling coefficient, load and the boundary resistance. First, the equivalent circuit as well as the steady-state and transient performance of Γ-source circuit breaker are analyzed. Then, the nonlinear segment equation of the boundary resistance for definition method through theoretical calculation and experimental data is fitted to avoid misoperation opening caused by load step change. Finally, the law between the transformer ratio, coupling coefficient, the load and the boundary resistance is obtained to define an accuracy short-circuit region. The feasibility and effectiveness of the proposed method have been verified using experimental results

    Biomass-derived carbon material as efficient electrocatalysts for the oxygen reduction reaction

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    Despite the abundance of carbon in nature, a significant portion of the existing biomass carbon materials in livestock, agriculture, and marine fishery industry are currently being wasted. Utilizing sustainable carbon materials as an alternative to noble Pt-based catalysts is crucial step to convert widely available and low-cost biomass resources into clean energy systems. Therefore, the rational synthesis of carbon-based catalysts for oxygen reduction reaction (ORR) has become a hot research focus in the field of electrochemistry. In this study, the recent progress in the synthesis of ORR electrocatalysts using sustainable biomass resources was reviewed; the activation and synthesis strategies of various biomass resources, as well as the microstructure and oxygen reduction performance of the prepared carbon-based catalysts were investigated. It is hoped that this review article will promote the understanding of various parameters from biomass as precursors for catalyst preparation and make contribute to the transition of biomass resources from the wasted carbon materials to the main catalysts in future energy devices.</p

    Effects of Visual Cues during Listening Comprehension with Chinese Learners of Advanced Japanese: An Experimental Study on Images and Key Words

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    Many studies have confirmed that visual cues provide considerable help to language learners in listening comprehension. However. no conclusion has yet been reached as to whether images or text are more effective as visual cues. The purpose of the present study was to examine and compare the different effects between verbal (text) and non-verbal (images) cues on listening comprehension. Twenty Chinese learners of advanced Japanese were divided into an image group or text group. Participants in the two groups were asked to examine related images or key words. while listening to the reading of three short articles in Japanese, each lasting around 1 minute. After one article was finished. the participants were asked to recall the content of the article in their mother tongue (LI) by writing it down immediately. They then answered true or false questions about the general ideas presented in the article. From a comparison of the test results of the two groups, the following conclusions were made. For these language learners who were proficient in Japanese. the image cues and text cues had almost have same effect in terms of listening comprehension. However. the image cues were clearly more effective than text cues in remembering the general ideas expressed in the article

    A novel FBN2 mutation in a Chinese family with congenital contractural arachnodactyly

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    AbstractCongenital contractural arachnodactyly (CCA, OMIM: 121050) is an autosomal dominant condition that shares skeletal features with Marfan syndrome (MFS, OMIM: 154700), including contractures, arachnodactyly, dolichostenomelia, scoliosis, crumpled ears and pectus deformities but excluding the ocular and cardiovascular complications that characterize MFS. These two similar syndromes result from mutations in two genes belonging to the fibrillin family, FBN1 and FBN2, respectively. We successfully identified a novel FBN2 mutation (C1406R) in a Chinese family with CCA for over five generations. This mutation was detected in the patients of this family but not in the seven unaffected family members or 100 normal individuals. SIFT and PolyPhen analyses suggested that the mutation was pathogenic. We identified a missense mutation in the calcium binding-epidermal growth factor (cbEGF)-like domain. Our study extends the mutation spectrum of CCA and confirms a relationship between mutations in the FBN2 gene and the clinical findings of CCA

    Construction of a Nomogram predictive model for post-discharge psychosomatic review of psychiatric liaison consultation patients based on medical record data

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    Epidemiological studies have shown that almost all physical illnesses coexist with psychiatric disorders or psychological problems, and the severity of mental illness is positively correlated with the duration and severity of physical illness. Liaison consultations are valuable in identifying and treating psychiatric disorders, but the rate of psychiatric follow-up after consultation is low in outpatients. This study aimed to investigate the factors influencing post-discharge psychosomatic follow-up visits in patients undergoing psychiatric liaison consultation in general hospitals and construct a Nomogram prediction model for patients’ post-discharge psychosomatic follow-up visits. Medical record data of inpatients who received psychiatric liaison consultations at Xi’an International Medical Center Hospital in China from September 2019 to September 2020 were analyzed. Lasso regression and multivariate logistic regression analyses were conducted to screen independent influences on the occurrence of post-discharge psychosomatic follow-ups in patients undergoing psychiatric liaison consultations. Risk prediction column line graphs were constructed using R software, and the models were evaluated. Of the 494 inpatients who received psychiatric liaison consultations, 115 patients (23.279%) (mean age = 54.8 years) went for post-discharge psychosomatic follow-up, while 379 patients (mean age = 59.3 years) had no record of psychosomatic follow-up. Furthermore, occupation, interval.time, diagnosis, out.antipsychotics, and recommendations.followup were independent factors influencing post-discharge psychosomatic follow-up. The model accurately predicted post-discharge psychosomatic follow-up behavior of inpatients who received psychiatric liaison consultations. Lastly, the clinical decision curve analysis showed that the model had good validity for clinical application. Patients who received a psychiatric liaison consultation with a ≤ 10-day interval between admission to the hospital and application for consultation, were discharged with prescribed medication, and had a clear written medical order for a follow-up consultation had an increased probability of psychosomatic follow-up after discharge

    Model-based analysis uncovers mutations altering autophagy selectivity in human cancer

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    Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis
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