Comparative genome analysis of PHB gene family reveals deep evolutionary origins and diverse gene function

<p>Abstract</p> <p>Background</p> <p>PHB (Prohibitin) gene family is involved in a variety of functions important for different biological processes. PHB genes are ubiquitously present in divergent species from prokaryotes to eukaryotes. Human PHB genes have been found to be associated with various diseases. Recent studies by our group and others have shown diverse function of PHB genes in plants for development, senescence, defence, and others. Despite the importance of the PHB gene family, no comprehensive gene family analysis has been carried to evaluate the relatedness of PHB genes across different species. In order to better guide the gene function analysis and understand the evolution of the PHB gene family, we therefore carried out the comparative genome analysis of the PHB genes across different kingdoms.</p> <p>Results</p> <p>The relatedness, motif distribution, and intron/exon distribution all indicated that PHB genes is a relatively conserved gene family. The PHB genes can be classified into 5 classes and each class have a very deep evolutionary origin. The PHB genes within the class maintained the same motif patterns during the evolution. With<it> Arabidopsis</it> as the model species, we found that PHB gene intron/exon structure and domains are also conserved during the evolution. Despite being a conserved gene family, various gene duplication events led to the expansion of the PHB genes. Both segmental and tandem gene duplication were involved in Arabidopsis PHB gene family expansion. However, segmental duplication is predominant in Arabidopsis. Moreover, most of the duplicated genes experienced neofunctionalization. The results highlighted that PHB genes might be involved in important functions so that the duplicated genes are under the evolutionary pressure to derive new function.</p> <p>Conclusion</p> <p>PHB gene family is a conserved gene family and accounts for diverse but important biological functions based on the similar molecular mechanisms. The highly diverse biological function indicated that more research needs to be carried out to dissect the PHB gene function. The conserved gene evolution indicated that the study in the model species can be translated to human and mammalian studies.</p

Intracranial injection of dengue virus induces interferon stimulated genes and CD8(+) T cell infiltration by sphingosine kinase 1 independent pathways

We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain. Body weight loss and DENV RNA level tended to be greater in SK1-/- compared with wildtype (WT) mice. Brain infection with DENV-2 is associated with the induction of interferon-β (IFN-β) and IFN-stimulated gene (ISG) expression including viperin, Ifi27l2a, IRF7, and CXCL10 without any significant differences between WT and SK1-/- mice. The SK2 and sphingosine-1-phosphate (S1P) levels in the brain were unchanged by DENV infection or the lack of SK1. Histological analysis demonstrated the presence of a cellular infiltrate in DENV-infected brain with a significant increase in mRNA for CD8 but not CD4 suggesting this infiltrate is likely CD8+ but not CD4+ T-lymphocytes. This increase in T-cell infiltration was not affected by the lack of SK1. Overall, DENV-infection in the brain induces IFN and T-cell responses but does not influence the SK/S1P axis. In contrast to our observations in vitro, SK1 has no major influence on these responses following DENV-infection in the mouse brain.Wisam H. Al-Shujairi, Jennifer N. Clarke, Lorena T. Davies, Mohammed Alsharifi, Stuart M. Pitson, Jillian M. Car

Feasibility and reliability of frailty assessment in the critically ill: a systematic review

Background. For healthcare systems, an ageing population poses challenges in the delivery of equitable and effective care. Frailty assessment has the potential to improve care in the intensive care setting, but applying assessment tools in critical illness may be problematic. The aim of this systematic review was to evaluate evidence for the feasibility and reliability of frailty assessment in critical care. Methods. Our primary search was conducted in Medline, Medline In-process, EMBASE, CINAHL, PsycINFO, AMED, Cochrane Database of Systematic Reviews, and Web of Science (January 2001 to October 2017). We included observational studies reporting data on feasibility and reliability of frailty assessment in critical care setting in patients 16 years and older. Feasibility was assessed in terms of timing of evaluation, the background, training and expertise required for assessors, and reliance upon proxy input. Reliability was assessed in terms of inter-rater reliability. Results. Data from 11 study publications are included, representing eight study cohorts and 7761 patients. Proxy involvement in frailty assessment ranged from 58- 100%. Feasibility data were not well-reported overall, but the exclusion rate due to lack of proxy availability ranged from 0 to 45%, the highest rate observed where family involvement was mandatory and the assessment tool relatively complex (Frailty Index, FI). Conventional elements of Frailty Phenotype (FP) assessment required modification prior to use in two studies. Clinical staff tended to use a simple judgement-based tool, the Clinical Frailty Scale (CFS). Inter-rater reliability was reported in one study using the CFS and although a good level of agreement was observed between clinician assessments, this was a small and single centre study. Conclusion. Though of unproven reliability in the critically ill, CFS was the tool used most widely by critical care clinical staff. Conventional FP assessment required modification for general application in critical care, and a FI-based assessment may be difficult to deliver by the critical care team on a routine basis. There is a high reliance on proxies for frailty assessment, and the reliability of frailty assessment tools in critical care needs further evaluation. PROSPERO CRD42016052073

Programmed cell death and its role in inflammation

Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases

Physical activity and maternal–fetal circulation measured by Doppler ultrasound

OBJECTIVE: To examine the association of physical activity on maternal-fetal circulation measured by uterine and umbilical artery Doppler flow velocimetry waveforms. STUDY DESIGN: Participants included 781 pregnant women with Doppler ultrasounds of the uterine and umbilical artery and who self-reported past week physical activity. Linear and generalized estimating equation regression models were used to examine these associations. RESULTS: Moderate-to-vigorous total and recreational activity were associated with higher uterine artery pulsatility index (PI) and an increased risk of uterine artery notching as compared to reporting no total or recreational physical activity, respectively. Moderate-to-vigorous work activity was associated with lower uterine artery PI and a reduced risk of uterine artery notching as compared to no work activity. No associations were identified with the umbilical circulation measured by the resistance index. CONCLUSION: In this epidemiologic study, recreational and work activity were associated with opposite effects on uterine artery PI and uterine artery notching, though associations were modest in magnitude

Avaliação da reprodutibilidade e validade de questionário de atividade física para gestantes Evaluation of the reproducibility and validity of a physical activity questionnaire for pregnant women

INTRODUÇÃO: A prática de atividade física tem sido incentivada por vários organismos nacionais e internacionais visando a promoção de saúde. Entretanto não existe consenso acerca da influência e da intensidade ótima de atividade física durante a gestação, possivelmente devido a dificuldades de mensuração e classificação do nível de atividade física através de questionários. Não se identificou qualquer estudo de validação de questionário de atividade física em gestantes no Brasil. O objetivo do presente estudo é analisar a reprodutibilidade e validade concorrente de um questionário de atividades físicas para gestantes. MÉTODOS: Em amostra de 68 gestantes, no segundo trimestre de gestação foi realizada entrevista para aplicação do questionário, que foi repetida com aproximadamente uma semana de intervalo e no puerpério. No período entre as duas primeiras entrevistas, as mulheres utilizaram monitor de freqüência cardíaca (n=38). RESULTADOS: As análises de reprodutibilidade foram adequadas com coeficientes de correlação intraclasse variando de 0,54 a 0,85. A análise das variáveis categóricas, com questões subjetivas e de autopercepção da atividade física, resultou em maior intervalo de coeficiente kappa com valores entre 0,29 e 0,76 entre a aplicação do questionário com uma semana de intervalo, e 0,08 a 0,70 comparado ao puerpério. As análises de validade conduziram a resultado satisfatório quanto à média das diferenças encontrada por intermédio do gráfico de Bland e Altman (1986) entre o questionário e o freqüencímetro. Entretanto, o intervalo da dispersão não se apresentou adequado, visto que variou em mais de sete horas para atividades leves e em quase onze horas por dia para atividades moderadas. As análises do presente estudo parecem assegurar a reprodutibilidade do questionário de atividade física para gestantes. No entanto, com relação à validação, a comparação com os resultados obtidos pelo freqüêncímetro não mostrou graus de concordância adequados.<br>INTRODUCTION: Physical activity practice has been encouraged by several national and international entities aiming health promotion. However, there is no consensus concerning the influence and optimal intensity of physical activity during pregnancy, probably due to difficulties to measure and classify the level of physical activity by questionnaires. It has not been identified any validation study of physical activity questionnaire on Brazilian pregnant women. The purpose of the present study is to analyze the reliability and concurrent validity of a physical activity questionnaire for pregnant women. METHODS: A sample of 68 women in the second trimester of pregnancy has been interviewed by the elaborated questionnaire. Reliability was assessed after approximately a week and in the postpartum. The subjects used a heart rate monitor between the two first interviews (n=38). RESULTS: Reproducibility analyses were adapted with interclass correlation coefficients varying from 0.54 to 0.85. The analysis of categorical variables, with subjective questions of self-perception of physical activity, resulted in wider range of kappa coefficients, with values between 0.29 and 0.76 for application of the questionnaire within one week of interval, and between 0.08 and 0.70 when compared with the postpartum. The validity analyses had a satisfactory result considering the average of differences seen through Bland-Altman graphics comparing questionnaire and the heart rate monitors. However, the dispersion interval was not adequate, since it varied in more than seven hours for light activities and almost eleven hours per day for moderate activities. Analyses of current study seem to assure the reliability of the physical activity questionnaire for pregnant women. However, concerning validation, the comparison with results obtained by heart rate monitors did not show adequate degrees of agreement