1,210 research outputs found

    Measuring the functional sequence complexity of proteins

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    <p>Abstract</p> <p>Background</p> <p>Abel and Trevors have delineated three aspects of sequence complexity, Random Sequence Complexity (RSC), Ordered Sequence Complexity (OSC) and Functional Sequence Complexity (FSC) observed in biosequences such as proteins. In this paper, we provide a method to measure functional sequence complexity.</p> <p>Methods and Results</p> <p>We have extended Shannon uncertainty by incorporating the data variable with a functionality variable. The resulting measured unit, which we call Functional bit (Fit), is calculated from the sequence data jointly with the defined functionality variable. To demonstrate the relevance to functional bioinformatics, a method to measure functional sequence complexity was developed and applied to 35 protein families. Considerations were made in determining how the measure can be used to correlate functionality when relating to the whole molecule and sub-molecule. In the experiment, we show that when the proposed measure is applied to the aligned protein sequences of ubiquitin, 6 of the 7 highest value sites correlate with the binding domain.</p> <p>Conclusion</p> <p>For future extensions, measures of functional bioinformatics may provide a means to evaluate potential evolving pathways from effects such as mutations, as well as analyzing the internal structural and functional relationships within the 3-D structure of proteins.</p

    The Universal Plausibility Metric (UPM) & Principle (UPP)

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    <p>Abstract</p> <p>Background</p> <p>Mere possibility is not an adequate basis for asserting scientific plausibility. A precisely defined universal bound is needed beyond which the assertion of <it>plausibility</it>, particularly in life-origin models, can be considered operationally falsified. But can something so seemingly relative and subjective as plausibility ever be quantified? Amazingly, the answer is, "Yes." A method of objectively measuring the plausibility of any chance hypothesis (The Universal Plausibility Metric [UPM]) is presented. A numerical inequality is also provided whereby any chance hypothesis can be definitively falsified when its UPM metric of ξ is < 1 (The Universal Plausibility Principle [UPP]). Both UPM and UPP pre-exist and are independent of any experimental design and data set.</p> <p>Conclusion</p> <p>No low-probability hypothetical plausibility assertion should survive peer-review without subjection to the UPP inequality standard of formal falsification (ξ < 1).</p

    Deletion of BmoR affects the expression of genes related to thiol/disulfide balance in Bacteroides fragilis

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    Bacteroides fragilis, an opportunistic pathogen and commensal bacterium in the gut, is one the most aerotolerant species among strict anaerobes. However, the mechanisms that control gene regulation in response to oxidative stress are not completely understood. In this study, we show that the MarR type regulator, BmoR, regulates the expression of genes involved in the homeostasis of intracellular redox state. Transcriptome analysis showed that absence of BmoR leads to altered expression in total of 167 genes. Sixteen of these genes had a 2-fold or greater change in their expression. Most of these genes are related to LPS biosynthesis and carbohydrates metabolism, but there was a signifcant increase in the expression of genes related to the redox balance inside the cell. A pyridine nucleotide-disulfde oxidoreductase located directly upstream of bmoR was shown to be repressed by direct binding of BmoR to the promoter region. The expression of two other genes, coding for a thiosulphate:quinoneoxidoreductase and a thioredoxin, are indirectly afected by bmoR mutation during oxygen exposure. Phenotypic assays showed that BmoR is important to maintain the thiol/disulfde balance in the cell, confrming its relevance to B. fragilis response to oxidative stress

    Massive thymic hemorrhage and hemothorax occurring in utero

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    Background: Thymic enlargement is a common and physiological finding in children and neonates' X-rays, but it is usually asymptomatic. Occasionally it can cause respiratory distress. In most cases the aetiology of this expansion remains unclear and it is diagnosed as a thymic hyperplasia. True thymic hyperplasia is defined as a gland expansion, both in size and weight, while maintaining normal microscopic architecture. Often it is a diagnosis of exclusion and prognosis is good. Thymic haemorrhage is an unusual condition related to high foetal and neonatal mortality. Case Presentation: We report a case of spontaneous massive thymic haemorrhage in a newborn developing at birth acute respiratory distress associated with severe bilateral haemothorax. Thymic enlargement was evident after pleural evacuation and confirmed by radiographic, Computed Tomography (CT) images and Magnetic Resonance Imaging (MRI) sequences. The spontaneous resolution of this enlargement seen with CT scan and MRI sequences suggested a thymic haemorrhage; surgery was not necessary. Conclusion: Thymic haemorrhage should be considered in newborn infants with pleural effusion, mediastinal space enlargement and Respiratory Distress

    Validação brasileira do Instrumento de Qualidade de Vida/espiritualidade, religião e crenças pessoais

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    OBJETIVO: Analisar propriedades psicométricas do Instrumento de Qualidade de Vida da Organização Mundial da Saúde - Módulo Espiritualidade, Religiosidade e Crenças Pessoais (WHOQOL-SRPB). MÉTODOS: O WHOQOL-SRPB, a Escala de Coping Religioso/Espiritual Abreviada (CRE-Breve), o WHOQOL-Breve e o BDI foram consecutivamente aplicados em amostra de conveniência de 404 pacientes e funcionários de hospital universitário e funcionários de universidade, em Porto Alegre, RS, entre 2006 e 2009. A amostra foi estratificada por sexo, idade, estado de saúde e religião/crença. O reteste dos dois primeiros instrumentos foi realizado com 54 participantes. Análises fatoriais exploratórias do WHOQOL-SRPB pelo método dos componentes principais foram realizadas sem delimitar o número de fatores, solicitando oito fatores e em conjunto com os itens do WHOQOL-Breve. RESULTADOS: O WHOQOL-SRPB em português brasileiro (Domínio SRPB-Geral) apresentou validade de construto, com validade discriminativa entre crentes de não-crentes (t = 7,40; p = 0,0001); validade relacionada ao critério concorrente, discriminando deprimidos de não-deprimidos (t = 5,03; p = 0,0001); validade convergente com o WHOQOL-Breve (com físico r = 0,18; psicológico r = 0,46; social r = 0,35; ambiental r = 0,29; global r = 0,23; p = 0,0001) e com o Domínio SRPB do WHOQOL-100 (r = 0,78; p = 0,0001); e validade convergente/discriminante com a Escala CRE-Breve (com CREpositivo r = 0,64; p = 0,0001/CREnegativo r = -0,03; p = 0,554). Observou-se excelente fidedignidade teste-reteste (t = 0,74; p = 0,463) e consistência interna (&#945; = 0,96; correlação intrafatorial 0,87 > r > 0,60, p = 0,0001). As análises fatoriais exploratórias realizadas corroboraram a estrutura de oito fatores do estudo multicêntrico do WHOQOL-SRPB. CONCLUSÕES: O WHOQOL-SRPB em português brasileiro apresentou boas qualidades psicométricas e uso válido e fidedigno para uso no Brasil. Sugerem-se novos estudos com populações específicas, como diferentes religiões, grupos culturais e/ou doenças.OBJETIVO: Analizar propiedades psicométricas del Instrumento de Calidad de Vida de la OMS - Módulo Espiritualidad, Religiosidad y Creencias Personales (WHOQOL-SRPB). MÉTODOS: El WHOQOL-SRPB, la Escala de Coping Religioso/Espiritual Abreviada (CRE-Breve), el WHOQOL-Breve y el BDI fueron consecutivamente aplicados en muestra de conveniencia de 404 pacientes y funcionarios de hospital universitario y funcionarios de universidad, en Porto Alegre, Sur de Brasil, entre 2006 y 2009. La muestra fue estratificada por sexo, edad, estado de salud y religión/creencia. La reevaluación de los dos primeros instrumentos fue realizada por 54 participantes. Análisis factoriales exploratorias del WHOQOL-SRPB por el método de los componentes principales fueron realizadas, sin delimitar el número de factores, solicitando ocho factores y en conjunto con los itens del WHOQOL-Breve. RESULTADOS: El WHOQOL-SRPB en portugués-brasileño (Dominio SRPB-General) presentó validez de constructo, con validez discriminativa entre creyentes de no creyentes (t=7,40; p=0,0001); validez relacionada con el criterio concurrente, discriminando deprimidos de no deprimidos (t=5,03; p=0,0001); validez convergente con el WHOQOL-Breve (con físico r=0,18; psicológico r=0,46; social r=0,35; ambiental r=0,29; global r=0,23; p=0,0001) y con el Dominio-SRPB del WHOQOL-100 (r=0,78; p=0,0001); y validez convergente/discriminante con la Escala CRE-Breve (con CRE positivo r=0,64; p=0,0001/CRE negativo r=-0,03; p=0,554). Se observó excelente fidedignidad test-retest (t=0,74; p=0,463) y consistencia interna (&#945;=0,96; correlación intrafactorial 0,87>r>0,60, p=0,0001). Los análisis factoriales exploratorios realizados corroboran la estructura de ocho factores de estudio multicéntrico del WHOQOL-SRPB. CONCLUSIONES: El WHOQOL-SRPB en portugués-brasileño presentó buenas cualidades psicométricas, siendo válido y fidedigno para uso en Brasil. Se sugieren nuevos estudios con poblaciones específicas, como diferentes religiones, grupos culturales y/o enfermedades.OBJECTIVE: To analyze the psychometric properties of the World Health Organization's Quality of Life Instrument - Spirituality, Religion and Personal Beliefs module (WHOQOL-SRPB). METHODS: The WHOQOL-SRPB, the Brief Spiritual/Religious Coping Scale (Brief-SRCOPE Scale), the WHOQOL-BREF and the Beck Depression Inventory (BDI) were consecutively applied in a convenience sample of 404 patients and workers of a university hospital and workers of a university, in the city of Porto Alegre, Southern Brazil, between 2006 and 2009. The sample was stratified by sex, age, health status and religion/belief. The retest of the two first instruments was conducted with 54 participants. Exploratory factorial analyses of the WHOQOL-SRPB with the method of main components were performed, without limiting the number of factors, and requiring eight factors concomitantly with the WHOQOL-BREF items. RESULTS: The Brazilian Portuguese version of the WHOQOL-SRPB (General SRPB-Domain) showed construct validity, with a discriminatory validity between believers and non-believers (t = 7.40; p = 0.0001); concurrent criterion-related validity, distinguishing depressed individuals from non-depressed ones (t = 5.03; p = 0.0001); convergent validity with the WHOQOL-BREF (physical r = 0.18; psychological r = 0.46; social r = 0.35; environmental r = 0.29; global r = 0.23; p = 0.0001) and with the SRPB-Domain of the WHOQOL-100 (r = 0.78; p = 0.0001); and convergent/discriminatory validity with the brief SRCOPE Scale (with positive SRCOPE r = 0.64; p = 0.0001/negative SRCOPE r = -0.03; p = 0.554). Excellent test-retest reliability (t = 0.74; p = 0.463) and internal consistency (&#945; = 0.96; intrafactorial correlation 0.87 > r > 0.60; p = 0.0001) were observed. The exploratory factorial analyses performed corroborated the eight-factor structure of the WHOQOL-SRPB multicenter study. CONCLUSIONS: The Brazilian Portuguese version of the WHOQOL-SRPB showed good psychometric qualities and use valid and reliable in Brazil. It is suggested that new studies be conducted with specific populations, such as different religions, cultural groups and/or diseases

    GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection

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    Cellular necrosis during Mycobacterium tuberculosis (Mtb) infection promotes both immunopathology and bacterial dissemination. Glutathione peroxidase-4 (Gpx4) is an enzyme that plays a critical role in preventing iron-dependent lipid peroxidation–mediated cell death (ferroptosis), a process previously implicated in the necrotic pathology seen in Mtb-infected mice. Here, we document altered GPX4 expression, glutathione levels, and lipid peroxidation in patients with active tuberculosis and assess the role of this pathway in mice genetically deficient in or overexpressing Gpx4. We found that Gpx4-deficient mice infected with Mtb display substantially increased lung necrosis and bacterial burdens, while transgenic mice overexpressing the enzyme show decreased bacterial loads and necrosis. Moreover, Gpx4-deficient macrophages exhibited enhanced necrosis upon Mtb infection in vitro, an outcome suppressed by the lipid peroxidation inhibitor, ferrostatin-1. These findings provide support for the role of ferroptosis in Mtb-induced necrosis and implicate the Gpx4/GSH axis as a target for host-directed therapy of tuberculosis

    Parenteral nutrition support for patients with pancreatic cancer. Results of a phase II study

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    <p>Abstract</p> <p>Background</p> <p>Cachexia is a common problem in patients (pts) suffering from upper gastrointestinal cancer. In addition, most of these patients suffer from malabsorption and stenosis of the gastrointestinal tract due to their illness. Various methods of supplementary nutrition (enteral, parenteral) are practised. In patients with advanced pancreatic cancer (APC), phase angle, determined by bio-electrical impedance analysis (BIA), seems to be a survival predictor. The positive influence of BIA determinate predictors by additional nutrition is currently under discussion.</p> <p>Methods</p> <p>To examine the impact of additional parenteral nutrition (APN) we assessed outpatients suffering from APC and progressive cachexia. The assessment based on the BIA method. Assessment parameters were phase angle, ECM/BCM index (ratio of extracellular mass to body cell mass), and BMI (body mass index). Patients suffering from progressive weight loss in spite of additional enteral nutritional support were eligible for the study.</p> <p>Results</p> <p>Median treatment duration in 32 pts was 18 [8-35] weeks. Response evaluation showed a benefit in 27 pts (84%) in at least one parameter. 14 pts (43.7%) improved or stabilised in all three parameters. The median ECM/BCM index was 1.7 [1.11-3.14] at start of APN and improved down to 1.5 [1.12-3.36] during therapy. The median BMI increased from 19.7 [14.4-25.9] to 20.5 [15.4-25.0]. The median phase angle improved by 10% from 3.6 [2.3-5.1] to 3.9 [2.2-5.1].</p> <p>Conclusions</p> <p>We demonstrated the positive impact of APN on the assessed parameters, first of all the phase angle, and we observed at least a temporary benefit or stabilisation of the nutritional status in the majority of the investigated patients. Based on these findings we are currently investigating the impact of APN on survival in a larger patient cohort.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00919659</p

    Planck intermediate results. XLI. A map of lensing-induced B-modes

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    The secondary cosmic microwave background (CMB) BB-modes stem from the post-decoupling distortion of the polarization EE-modes due to the gravitational lensing effect of large-scale structures. These lensing-induced BB-modes constitute both a valuable probe of the dark matter distribution and an important contaminant for the extraction of the primary CMB BB-modes from inflation. Planck provides accurate nearly all-sky measurements of both the polarization EE-modes and the integrated mass distribution via the reconstruction of the CMB lensing potential. By combining these two data products, we have produced an all-sky template map of the lensing-induced BB-modes using a real-space algorithm that minimizes the impact of sky masks. The cross-correlation of this template with an observed (primordial and secondary) BB-mode map can be used to measure the lensing BB-mode power spectrum at multipoles up to 20002000. In particular, when cross-correlating with the BB-mode contribution directly derived from the Planck polarization maps, we obtain lensing-induced BB-mode power spectrum measurement at a significance level of 12σ12\,\sigma, which agrees with the theoretical expectation derived from the Planck best-fit Λ\LambdaCDM model. This unique nearly all-sky secondary BB-mode template, which includes the lensing-induced information from intermediate to small (10100010\lesssim \ell\lesssim 1000) angular scales, is delivered as part of the Planck 2015 public data release. It will be particularly useful for experiments searching for primordial BB-modes, such as BICEP2/Keck Array or LiteBIRD, since it will enable an estimate to be made of the lensing-induced contribution to the measured total CMB BB-modes.Comment: 20 pages, 12 figures; Accepted for publication in A&A; The B-mode map is part of the PR2-2015 Cosmology Products; available as Lensing Products in the Planck Legacy Archive http://pla.esac.esa.int/pla/#cosmology; and described in the 'Explanatory Supplement' https://wiki.cosmos.esa.int/planckpla2015/index.php/Specially_processed_maps#2015_Lensing-induced_B-mode_ma
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