An in silico investigation of phytochemicals as potential inhibitors against non-structural protein 1 from dengue virus 4

Dengue fever has emerged as a big threat to human health since the last decade owing to high morbidity with considerable mortalities. The proposed study aims at the in silico investigation of the inhibitory action against DENV4-NS1 of phytochemicals from two local medicinal plants of Pakistan. Non-Structural Protein 1 of Dengue Virus 4 (DENV4-NS1) is known to be involved in the replication and maturation of viron in the host cells. A total of 129 phytochemicals (50 from Tanacetum parthenium and 79 from Silybum marianum) were selected for this study. The tertiary structure of DENV4-NS1 was predicted based on homology modelling using Modeller 9.18 and the structural stability was evaluated using molecular dynamics simulations. Absorption, distribution, metabolism, excretion and toxicity (ADMET) along with the drug-likeness was also predicted for these phytochemicals using SwissADME and PreADMET servers. The results of ADMET and drug-likeness predictions exhibited that 54 phytochemicals i.e. 25 from Tanacetum parthenium and 29 from Silybum marianum showed effective druglikeness. These phytochemicals were docked against DENV4-NS1 using AutoDock Vina and 18 most suitable phytochemicals with binding affinities ≤ -6.0 kcal/mol were selected as potential inhibitors for DENV4-NS1. Proposed study also exploits the novel inhibitory action of Jaceidin, Centaureidin, Artecanin, Secotanaparthenolide, Artematin, Schizolaenone B, Isopomiferin, 6, 8-Diprenyleriodictyol, and Anthraxin against dengue virus. It is concluded that the screened 18 phytochemicals have strong inhibition potential against Dengue Virus 4.

Exigência de proteína bruta para juvenis de curimatã-pacu / Crude protein requeriment to curimatã-pacu juveniles

O objetivo deste estudo foi determinar a exigência de proteína bruta (PB) de juvenis de curimatã-pacu (Prochilodus argenteus). O experimento foi conduzido por um período de 60 dias, utilizando um delineamento inteiramente ao acaso, com quatro tratamentos (dieta contendo 24,0; 28,0; 32,0 e 36,0% de PB) e cinco repetições cada, em que 100 juvenis (peso inicial de 0,33 ± 0,01g) foram distribuídos em 20 aquários experimentais com volume de 130L, sendo considerada como unidade experimental uma caixa com cinco peixes, sob recirculação de água. Avaliaram-se o desempenho produtivo, o crescimento heterogêneo, os parâmetros morfométricos, fisiológicos e a viabilidade econômica das rações em função do nível de PB. Pela análise de regressão, foi verificado um aumento linear nos parâmetros de desempenho, morfométricos e fisiológicos, com o aumento do nível proteico nas rações. Quando comparados pelo teste de Tukey, o melhor resultado (P>0,05) foi obtido com 36% de PB. Verificou-se menor heterogeneidade de crescimento dos peixes à medida que se aumentavam os níveis de PB na ração. Assim, considerando também a viabilidade econômica, recomenda-se a utilização de rações com 36% de proteína bruta para juvenis de curimatã-pacu.(AU)

The aim of this study was to determinate crude protein (CP) requirement to curimatã-pacu juveniles (Prochilodus argenteus). The experiment was conducted during 60 days in a completely randomized design, with four treatments (24.0, 28.0, 32.0 and 36.0% CP of diet) and five replications, where a hundred juvenile fishes (initial weight de 0.33 ± 0.01g), were distributed in twenty tanks (130L each). Each tank with five juveniles was considered an experimental unit, with water recirculation. Performance, heterogeneous growth, morphometric and physiological parameters, and economic viability of the rations according to the CP levels were evaluated. For the regression analysis, a linear increase in performance, heterogeneous growth and morphometric and physiological parameters with increased of the protein in rations were observed. When compared by the Tukey test (P>0.05), the best results were obtained with 36% CP. There was lower fish growth heterogeneity as the levels of CP in the diet increased. Thus, taking into consideration the economic viability it is recommended to use feed containing 36% of crude protein to curimatã-pacu juveniles.(AU)

Nucleotide sequence analysis of NIPBL gene in Indian Cornelia de Lange syndrome cases.

BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder in children. The disorder is caused mainly due to mutations in Nipped-B-like protein. The molecular data for CdLS is available from developed countries, but not available in developing countries like India. In the present study, the hotspot region of NIPBL gene was screened by Polymerase Chain Reaction which includes exon 2, 22, 42, and a biggest exon 10, in six CdLS patients and ten controls. MATERIALS AND METHODS: The method adopted in present study was amplification of the target exon by using polymerase chain reaction, qualitative confirmation of amplicons by Agarose Gel Electrophoresis and use of amplicons for Conformation Sensitive Gel Electrophoresis to find heteroduplex formation followed by sequencing. RESULTS: We report two polymorphisms in the studied region of gene NIPBL. The polymorphisms are in the region of intron 1 and in exon 10. The polymorphism C/A is present in intron 1 region and polymorphism T/G in exon 10. CONCLUSION: The intronic region polymorphism may have a role in intron splicing whereas the polymorphism in exon 10 results in amino acid change (Val to Gly). These polymorphisms are disease associated as these are found in CdLS patients only and not in controls.

Necesidades de nutrientes en la alimentación del niño con cáncer / Nutritional requirements in feeding the child with cancer

Los niños con cáncer se ven muy comprometidos en su alimentación en cuanto al consumo de proteínas y calorías. Las proteínas deben ser consumidas en cantidades suficientes de acuerdo a lo recomendado por la nutricionista infantil en su plan de alimentación. Las necesidades calóricas del niño con cáncer dependen de la edad, el peso, el estado nutricional, la actividad, el tipo de cáncer, las complicaciones y el estado del niño, entre otros, por lo que la nutricionista infantil junto con el pediatra, indicarán cómo ofrecer estas calorías al niño.

Children with cancer are very committed to their food in the consumption of protein and calories. Protein should be eaten in sufficient quantities in accordance with the recommendations of child nutrition in your food plan. Caloric needs of children with cáncer depends on age, weight, utritional status, type of cancer, complications and the child's condition, amongothers, so the child nutritionist with the pediatrician,tell you how to deliver these calories a child.

Sistema NADPH oxidasa: nuevos retos y perspectivas / NADPH oxidase system: new challenges and perspectives

El sistema NADPH oxidasa es un complejo multiproteico encargado de producir especies reactivas del oxígeno (ROS, por reactive oxygen species) en diferentes células y tejidos. Es de gran importancia en las células fagocíticas (principalmente neutrófilos y macrófagos) porque participa en la destrucción de microorganismos patógenos, mediante la fagocitosis y la formación de las trampas extracelulares de neutrófilos (NET, por neutrophils extracelular traps), así como en la activación de procesos inflamatorios. Las alteraciones en la producción de ROS por parte de las células fagocíticas a causa de defectos genéticos en los componentes del sistema generan la inmunodeficiencia primaria denominada enfermedad granulomatosa crónica (EGC). Este es un artículo de revisión sobre los componentes del sistema NADPH oxidasa, su distribución celular, mecanismo de activación y acción, así como de las funciones que desempeña en otros tejidos. Además, se revisan los defectos moleculares que llevan a la EGC y el tratamiento de esta, incluyendo la terapia con IFNγ, y finalmente las perspectivas para el estudio del sistema.

The NADPH oxidase system is a multiprotein complex that acts as the main source of reactive oxygen species (ROS) in different cells and tissues. In phagocytic cells (mainly macrophages and neutrophils) it is essential for eliminating pathogenic microorganisms, by phagocytosis and the formation of neutrophil extracellular traps (NETs). It also contributes to inflammatory processes. Genetic defects in the components of the system cause alterations in the production of ROS by phagocytic cells, leading to the primary immunodeficiency known as chronic granulomatous disease (CGD). This is a review article on the components of the NADPH oxidase system, its cellular distribution, activation, mechanisms of action, and roles in other tissues. The different molecular defects that lead to EGC are also reviewed, as well as its treatment, including therapy with IFNγ, and the prospects for the study of the system.

Using linear algebra for protein structural comparison and classification

In this article, we describe a novel methodology to extract semantic characteristics from protein structures using linear algebra in order to compose structural signature vectors which may be used efficiently to compare and classify protein structures into fold families. These signatures are built from the pattern of hydrophobic intrachain interactions using Singular Value Decomposition (SVD) and Latent Semantic Indexing (LSI) techniques. Considering proteins as documents and contacts as terms, we have built a retrieval system which is able to find conserved contacts in samples of myoglobin fold family and to retrieve these proteins among proteins of varied folds with precision of up to 80 percent. The classifier is a web tool available at our laboratory website. Users can search for similar chains from a specific PDB, view and compare their contact maps and browse their structures using a JMol plug-in.

Classificação de coeficientes de variação na experimentação com nutrição de eqüinos / Classification of the coefficient of variation in experimentation with equine nutrition

Foi realizada a classificação de coeficientes de variação dos coeficientes de digestibilidade da matéria seca, matéria orgânica, proteína bruta, fibras em detergente neutro e ácido, energia bruta, fibra bruta, celulose, hemicelulose, lignina, extrato etéreo e ganho de peso diário, com base em artigos científicos e teses em eqüinocultura. Os coeficientes de variação foram classificados em: baixo [<(m-1DP)]; médio [(m-1D)(m+2DP)]. Todas as respostas medidas apresentaram distribuição normal pelo teste Lilliefors. Quanto aos coeficientes de digestibilidade da fibra em detergente neutro e celulose, houve concordância entre a classificação proposta e a sugerida na literatura, sendo os mais discrepantes os coeficientes de digestibilidade da energia bruta e lignina. Desse modo, para cada variável analisada existe distribuição diferenciada dos coeficientes de variação, o que sugere a necessidade de classificação específica para as respostas medidas em nutrição de eqüinos.

Coefficients of variation (CV) distribution for several variables in equine nutrition were obtained. The data are from theses and published scientific papers in equine nutrition. The CV were classified as low [CV£(m-1sd)]; medium [(m-1sd)(m+2sd)]. The Lilliefors test for all variables showed no discrepancy from normal distribution. The distributions obtained for coefficients of digestibility for cellulose and fibre in neutral and acid detergent, were close enough to the classification suggested in the literature. However, the distributions for coefficient of digestibility for gross energy and lignin, showed high discrepancies from this classification suggesting that trial precision should be evaluated according to the variable considered. There is a different distribution for coefficients of variation for each variable suggesting the need of specific classification for each characteristic in equine studies.

Valoracion nutricional de 10 variedades de Quinua Chenopodium quinoa Willd del altiplano boliviano / Nutricional valuation of 10 varieties of Quinua Chenopodium quinoa Willd of the Bolivian plateau

El presente trabajo de investigación se desarrollo con el propósito de dar a conocer y difundir las características y propiedades nutritivas de 10 variedades de quinua (chenopodiurn qtunoa) propias de nuestra región (altiplano boliviano). La valoración comprendió el estudio de la naturaleza bioquímica el producto mediante evaluaciones de las propiedades químicas y nutritivas. Los resultados de este estudio muestran que estas, son mayores en rendimientos de proteínas (14 -18 porciento) en referencia a los reportados en la bibliografía (6) (13 porciento) como promedio. Se destaca que la Variedad REAL BLANCA presenta un 17 porciento y AJARA 18 porciento en proteínas, asimismo presentan los mas altos rendimientos respecto a la composición de sus macro nutrientes y micro nutrientes como Vitaminas como la tiamina 0.56mg/ lOOg en la REAL BLANCA y Oligoelementos como el Calcio, Magnesio, Manganeso en la variedad AJARA

Application of InterPro for the functional classification of the proteins of fish origin in SWISS-PROT and TrEMBL.

InterPro (http://www.ebi.ac.uk/interpro/) is an integrated documentation resource for protein families, domains and sites, developed initially as a means of rationalizing the complementary efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. It is a useful resource that aids the functional classification of proteins. Almost 90% of the actinopterygii protein sequences from SWISS-PROT and TrEMBL can be classified using InterPro. Over 30% of the actinopterygii protein sequences currently in SWISS-PROT and TrEMBL are of mitochondrial origin, the majority of which belong to the cytochrome b/b6 family. InterPro also gives insights into the domain composition of the classified proteins and has applications in the functional classification of newly determined sequences lacking biochemical characterization, and in comparative genome analysis. A comparison of the actinopterygii protein sequences against the sequences of other eukaryotes confirms the high representation of eukaryotic protein kinase in the organisms studied. The comparisons also show that, based on InterPro families, the trans-species evolution of MHC class I and II molecules in mammals and teleost fish can be recognized.

Bases moleculares del proceso de muerte celular programada: implicaciones de la proteína supresora de tumores p53 y otras proteínas en el control del ciclo celular: mecanismos de acción apoptótica: revisión / Molecular bases of programmed cell death: involvement of tumor suppresor protein p53 and other proteins in the control of the cellular cycle: review

La apoptosis es un mecanismo de daño celular que ocurre en el normal desarrollo y en la regulación de tejidos y órganos en vertebrados. Neuronas bajo apoptosis dependiente o independiente de p53, dependiendo UPON del estímulo que conduce a fragmentación del DNA. Muchas neuronas en el desarrollo del sistema nervioso sufren apoptosis, siendo la ciclina D1 un esencial mediador del daño celular neural. Otras características de apoptosis son la condensación del núcleo, la fragmentación de la cromatina junto a los sitios de ruptura en los nucleosomas, la rotura de la membrana y la formación de cuerpos apoptóticos. Entre los posibles mecanismos moleculares estan: (a) la activación de proteasas, como ICE (II-1 ß converting enzyme); y una pequeña Ribonucleoproteína U1, siendo sustratos para ICE y sus homólogos (tales como ICH y otras proteínas). El gen p53 codifica un factor de transcripción que contribuye a varias diferentes actividades celulares, incluyendo la opoptosis, la respuesta celular a la radiación, y la actividad de proteínas tales como GADD, Bcl-2 (represor de apoptosis) y Bax. p53 ejecuta un papel como un inhibidor de apoptosis por transactivación de la expresión del gen Bax. El gen supresor de tumores p53 limita la proliferación celular por parada del ciclo celular en G1, o por apoptosis, dependiendo del contexto celular. La proteína p21 es un inhibidor de ciclinas dependientes de kinasas, la cual es transactivada por p53. Durante la apoptosis hay una activación de c-myc, y del factor de transcripción NF-kB (factor nuclear kappa ß), el cual es un importante regulador de la apoptosis. Como un ejemplo de señalización apoptosis nosotros hemos seleccionado el problema relatando el sistema Fas/APO en timocitos