Determinação de genes mórbidos e drogáveis a partir da construção e análise da rede integrada de interações moleculares entre genes humanos

The discovering process of new morbid genes and new target proteins for drugs have been shown to be very costly and laborious. Having in view cutting costs and speeding up this process, we propose, in this work, a new method to determine the gene druggability score and morbidity score, the probabilities of the protein encoded by the gene have the characteristics that make it a new target for drugs and in case of an alteration in that gene, we observed a phenotype that characterizes a genetic based illness. To determine these characteristics, we built, analyzed and determined the characteristics of the topology of the integrated molecular interactions network among human genes containing physical interactions between proteins, metabolic interactions and interactions of transcriptional regulation, and included other data such as level of gene transcription and cellular localization of the protein encoded by the gene. We tested our model in training sets and achieved results equal or better than the ones achieved by similar methods in the literature. Finally, with the purpose of investigating whether the assigned scores resembles the potential druggabilities and morbities of the previously unclassi ed genes, we looked for evidences in biomedical literature supporting the potential druggability and morbidity status of genes with the 10 highest scores. We found clear evidences for 73% and 90% of potential druggable and morbid genes respectively

Análisis de la región intergénica ARNr 16-23S y del gen ARNr 23S en cepas de campo de Mycroplasma hyopneumoniae : estudio filogenético de los micoplasmas porcinos en base al gen ARNr 23S

Programa de doctorado: Sanidad animal

AVALIAÇÃO DE GENÓTIPOS DE SERINGUEIRA (Hevea spp.) AO Microcyclus ulei VISANDO À IDENTIFICAÇÃO DE FONTES DE RESISTÊNCIA HORIZONTAL

Avaliou-se, sob condições controladas, a resistência de genótipos de seringueira ao mal-das-folhas. Empregaram-se dois isolados de Microcyclus ulei, pertencentes aos grupos I e II. Utilizaram-se mudas em sacos plásticos e inocularam-se folíolos nos estádios B1/B2 com uma suspensão de 2 χ 105conídios/ml. Incubaram-se as mudas em câmara úmida a 24° C por 24 horas. Determinaram-se o período latente (PL), diâmetro das lesões (DL), tipo de lesão (TL) e tipo de reação (TR). A maioria dos genótipos testados foi suscetível a pelo menos um isolado do patógeno. Os genótipos que apresentaram resistência moderada, com maior período latente e menor esporulação a um isolado, em geral, foram suscetíveis ao outro. Apenas o genotipo AM/86/271 exibiu resistência incompleta, caracterizada por maior PL, menor DL e baixa esporulação. Entretanto, o número de isolados testados não assegurou o caráter da resistência. Com base nos resultados obtidos concluiu-se que os genótipos avaliados não apresentaram perspectivas para utilização em programas de melhoramento visando resistência ao M.ulei.

Joergensenium rotatile n. gen., n. sp (Entactinaria, Radiolaria): its distribution in west Norwegian fjords

A new radiolarian genus and species, Joergensenium rotatile, is described. This species is restricted to recent sediments and plankton samples from the North Atlantic. Its recent distribution in the Norwegian Sea and West Norwegian fjords shows a strong affinity to the neritic province and reaches almost 2% in Hryangerfjord. This species is only known from late Glacial and Holocene sediments in the Nordic seas. This genus shows, however, a patchy stratigraphic distribution with its first occurrence in the south-west Pacific within Palcocene, in the Middle to Late Miocene from the Norwegian Sea, and in the Labrador Sea at the base of biozone NN 21. Two fjords are compared for the general radiolarian distribution, but with special emphasis on the occurrence of J. rotatile in both sediment and plankton.

Base genética de la cistinuria, heterogeneidad genética

La cistinuria es una aminoaciduria que se transmite de forma autosómica rececesiva. Clínicamente se distinguen 3 formas de cistinuria, tipos I, II y III. Inicialmente identificamos un gen, implicado en el transporte de cistina y aminoácidos básicos, rBAT como responsable de esta enfermedad. Hasta la fecha se han identificado 22 mutaciotles en rBAT responsables de cistinuria. Mediante estudios de mutaciones y ligamiento genético en familias con cistinuria hemos podido demostrar que la enfermedad es heterogénea. Sólo la cistinuria de tipo I se debe a mutaciones en rBAT, mientras otros genes serán responsables de los tipos II y III. Actualmente estamos realizando estudios de exclusión genética en familias tipo no I, que nos permitirían asignar las regiones cromosómicas en las que se encuentran el gen o los genes responsables de cistinuria tipo II y/o III, paso previo para poder aislar y caracterizar dichos genes.

Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.

Reflexiones en torno a algunas propuestas de caracterizaci??n gen??rica de la educaci??n no formal

Resumen tomado de la publicaci??n

La Prehistoria : nuestros or??genes : la base de la tolerancia

Tercer premio en la convocatoria de Premios Nacionales a la innovaci??n educativa 2003

Saccharospirillum impatiens gen. nov., sp nov., a novel gamma-Proteobacterium isolated from hypersaline Ekho Lake (East Antarctica)

Five Gram-negative, motile, aerobic to microaerophilic spirilla were isolated from various depths of the hypersaline, heliothermal and meromictic Ekho Lake (East Antarctica). The strains are oxidase- and catalase-positive, metabolize a variety of sugars and carboxylic acids and have an absolute requirement for sodium ions. The predominant fatty acids of the organisms are C-16: (1)omega7c, C-16:0 and C(18:1)omega7c, with C-10:1 3-OH, C-10:0 3-OH, C-12:0 3-OH, C-14:1 3-OH, C-14:0 3-OH and C-19:1 present in smaller amounts. The main polar lipids are diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylmonomethylamine. The DNA base composition of the strains is 54-55 mol% G + C. 16S rRNA gene sequence comparisons show that the isolates are related to the genera Oceanospirillum, Pseudospirillum, Marinospirillum, Halomonas and Chromohalobacter in the gamma-Proteobacteria. Morphological, physiological and genotypic differences from these previously described genera support the description of a novel genus and species, Saccharospirillum impatiens gen. nov., sp. nov. The type strain is EL-105(T) (= DSM 12546(T) = CECT 5721(T)).

Allobaculum stercoricanis gen. nov., sp nov., isolated from canine feces

Morphological, biochemical, and molecular genetic studies were performed on an unknown anaerobic, catalase-negative, nonspore-forming, rod-shaped bacterium isolated from dog feces. The unknown bacterium was tentatively identified as a Eubacterium species, based on cellular morphological and biochemical tests. 16S rRNA gene sequencing studies, however, revealed that it was phylogenetically distant from Eubacterium limosum, the type species of the genus Eubacterium. Phylogenetically, the unknown species forms a hitherto unknown sub-line proximal to the base of a cluster of organisms (designated rRNA cluster XVI), which includes Clostridium innocuum, Streptococcus pleomorphus, and some Eubacterium species. Based on both phenotypic and phylogenetic criteria, it is proposed that the unknown bacterium be classified as a new genus and species, Allobaculum stercoricanis. Using a specific rRNA-targeted probe designed to identify Allobacultan stercoricanis, in situ hybridisation showed this novel species represents a significant organism in canine feces comprising between 0.1% and 3.7% of total cells stained with DAPI (21 dog fecal samples). The type strain of Allobaculum stereoricanis is DSM 13633(T) = CCUG 45212(T). (C) 2004 Elsevier Ltd. All rights reserved.

Anaerofustis stercorihominis gen. nov., sp nov., from human faeces

Phenotypic and phylogenetic studies were performed on an unidentified Gram-positive, strictly anaerobic, non-spore-forming, rod-shaped bacterium isolated from human feces. The organism was catalase-negative, resistant to 20% bile, produced acetic and butyric acids as end products of glucose metabolism, and possessed a G + C content of approximately 70 mol %. Comparative 16S rRNA gene sequencing demonstrated that the unidentified bacterium was a member of the Clostridium sub-phylum of the Gram-positive bacteria, and formed a loose association with rRNA cluster XV. Sequence divergence values of 12% or greater were observed between the unidentified bacterium and all other recognized species within this and related rRNA clusters. Treeing analysis showed the unknown anaerobe formed a deep line branching near to the base of rRNA cluster XV and phylogenetically represents a hitherto unknown taxon, distinct from Acetobacterium, Eubacterium sensu stricto, Pseudoramibacter and other related organisms. Based on both phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium from feces be classified in a new genus Anaerofustis, as Anaerofustis stercorihominis sp. nov. The type strain of Anaerofustis stercorihominis is ATCC BAA-858(T) = CCUG 47767(T). (C) 2003 Elsevier Ltd. All rights reserved.

A putative gnetalean gymnosperm Cariria orbiculiconiformis gen. nov et spec. nov from the Early Cretaceous of northern Gondwana

Cariria orbiculiconiformis gen. nov. et spec. nov., a gymnosperm with gnetoid characters is described from the upper Aptian Crato Formation of the Araripe Basin in northeastern Brazil. Gross-morphology and anatomical details have been studied and characters have been discussed in respect to various seed plants. Several of these characters fit best with those of Gnetales and their putative fossil allies. However, the fossil plant cannot be assigned to any known extinct or extant group of seed plants in their current circumscription. Stem gross-morphology, xylotomical characters and epidermal features indicate a gnetophytic relationship, whereas characters of the reproductive organs are rather distinct from those found in extant taxa. The reproductive unit of the new taxon represents a triple organ consisting of two dichasial ovulate structures and one median pollen-producing structure containing smooth, monosulcate, boat-shaped pollen in-situ. Each ovulate structure consists of two distinct pairs of bracts, a sterile one at the base and a fertile one forming a terminal orbicular capsule. Stiff processes found in the apex of the ovulate structure may represent micropylar tubes of seeds, as seen in the Bennettitales-Erdtmanithecales-Gnetales group. C orbiculiconiformis gen. nov. et spec. nov. was ans herbaceous or semi-shrub-like plant that may have been adapted to the r-strategy in a stressful environment. (C) 2011 Elsevier B.V. All rights reserved.

Lt Gen Ned Almond, USA : a ground commander's conflicting view with airmen over CAS doctrine and employment /

"August 1997."

Alternativas botánica, biológica y química para el manejo de piojo del tomate (Halticus sp) (Hemíptera: Miridae) y mosca blanca (Bemisia tabaci, Gen) (Hemiptera: Aleyroridae) en el cultivo de tomate (Solanum lycopersicum L.), bajo condiciones de casa malla.

El piojo del tomate (Halticus sp.) y la mosca blanca (Bemisia tabaci) son los principales agentes de daño, causantes de problemas fitosanitarios severos para los productores de tomate (Solanum lycopersicum, L), bajo condiciones de casa malla. Esta plaga provoca importantes pérdidas económicas, disminuyendo así los rendimientos al afectar la calidad de los frutos lo cual incide en mayores costos de producción. En base a esta problemática en el CEVAT (Centro de Experimentación y Validación de Tecnologías), UNA, se realizó un estudio en el período comprendido entre los meses de Septiembre 2015 a Enero 2016, con el objetivo de evaluar insecticidas biológico, botánico y químico contra el piojo del tomate y mosca blanca. Los productos evaluados fueron: Engeo, Madero Negro y Metarhizium anisopliae. Las variables evaluadas fueron: número de Halticus sp por planta, incidencia del daño por Halticus sp por planta, numero de mosca blanca por planta, incidencia del daño de virosis por planta, severidad del daño de virosis por planta. De los tratamientos evaluados, el menor promedio de piojo del tomate por planta lo presentó el tratamiento Engeo y de igual manera en mosca blanca, seguido de madero negro. El menor porcentaje de incidencia y severidad lo presentó el tratamiento Engeo en comparación con los demás tratamientos evaluados. El análisis económico realizado determinó que los tratamientos que presentaron los mejores rendimientos fueron Engeo con 18,156.25 kg/ha, seguido por Madero Negro con 16,891 kg/ha y Metarhizium anisopliae que obtuvo 14,797 kg/ha. Engeo presentó el mayor beneficio neto con 16,642.92 US$/ha, seguido por Madero Negro con 15,240.86 US$/ha. En el análisis de la tasa de retorno marginal resultó que el tratamiento Madero Negro es el que obtuvo la mejor tasa de retorno marginal con 6,307.36 % es decir 63.07 US$ por cada dólar invertido.

Encephalization And Diversification Of The Cranial Base In Platyrrhine Primates.

The cranial base, composed of the midline and lateral basicranium, is a structurally important region of the skull associated with several key traits, which has been extensively studied in anthropology and primatology. In particular, most studies have focused on the association between midline cranial base flexion and relative brain size, or encephalization. However, variation in lateral basicranial morphology has been studied less thoroughly. Platyrrhines are a group of primates that experienced a major evolutionary radiation accompanied by extensive morphological diversification in Central and South America over a large temporal scale. Previous studies have also suggested that they underwent several evolutionarily independent processes of encephalization. Given these characteristics, platyrrhines present an excellent opportunity to study, on a large phylogenetic scale, the morphological correlates of primate diversification in brain size. In this study we explore the pattern of variation in basicranial morphology and its relationship with phylogenetic branching and with encephalization in platyrrhines. We quantify variation in the 3D shape of the midline and lateral basicranium and endocranial volumes in a large sample of platyrrhine species, employing high-resolution CT-scans and geometric morphometric techniques. We investigate the relationship between basicranial shape and encephalization using phylogenetic regression methods and calculate a measure of phylogenetic signal in the datasets. The results showed that phylogenetic structure is the most important dimension for understanding platyrrhine cranial base diversification; only Aotus species do not show concordance with our molecular phylogeny. Encephalization was only correlated with midline basicranial flexion, and species that exhibit convergence in their relative brain size do not display convergence in lateral basicranial shape. The evolution of basicranial variation in primates is probably more complex than previously believed, and understanding it will require further studies exploring the complex interactions between encephalization, brain shape, cranial base morphology, and ecological dimensions acting along the species divergence process.