Contrasting 5' and 3' Evolutionary Histories and Frequent Evolutionary Convergence in Meis/hth Gene Structures

Organisms show striking differences in genome structure; however, the functional implications and fundamental forces that govern these differences remain obscure. The intron–exon organization of nuclear genes is involved in a particularly large variety of structures and functional roles. We performed a 22-species study of Meis/hth genes, intron-rich homeodomain-containing transcription factors involved in a wide range of developmental processes. Our study revealed three surprising results that suggest important and very different functions for Meis intron–exon structures. First, we find unexpected conservation across species of intron positions and lengths along most of the Meis locus. This contrasts with the high degree of structural divergence found in genome-wide studies and may attest to conserved regulatory elements residing within these conserved introns. Second, we find very different evolutionary histories for the 5′ and 3′ regions of the gene. The 5′-most 10 exons, which encode the highly conserved Meis domain and homeodomain, show striking conservation. By contrast, the 3′ of the gene, which encodes several domains implicated in transcriptional activation and response to cell signaling, shows a remarkably active evolutionary history, with diverse isoforms and frequent creation and loss of new exons and splice sites. This region-specific diversity suggests evolutionary “tinkering,” with alternative splicing allowing for more subtle regulation of protein function. Third, we find a large number of cases of convergent evolution in the 3′ region, including 1) parallel losses of ancestral coding sequence, 2) parallel gains of external and internal splice sites, and 3) recurrent truncation of C-terminal coding regions. These results attest to the importance of locus-specific splicing functions in differences in structural evolution across genes, as well as to commonalities of forces shaping the evolution of individual genes along different lineages

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Información Investigador: Burguera Moyonta, José Luis

Resumen Curricular Licenciado en Química de la Universidad de Bucarest, Rumania. Ph.D. en la Universidad de Birmingham, Inglaterra. Profesor Titular de la Universidad de Los AndesDoctorado0003IV - 2002207 - 2005; 154 - 2003; 274 - 2001Espectroscopia, Inyección en flujo, Elementos trazas. Química analítica.Noviembre de 2005Químico+58 274 2401286;+58 274 2401375Facultad de [email protected]

Lead concentration on the blood and urines of workers at petrol stations, Trujillo City, Venezuela.

CONTENIDO Editorial Linares de Gómez, Rosalba Artículos Concepciones del docente y problemática en la enseñanza de la geografía: educación media, diversificada y profesional. Educational conceptions and problems in the teaching of geography: media, diversified and professional education. Santiago Rivera, José Armando Praxis investigativa geohistórica para una representación cartográfica de un espacio rural. Geohistorical research praxis on a cartographic representation of rural space. Palencia, Yamili del Carmen Mirada geohistórica de Venezuela en la obra de Alejandro Von Humboldt. Geohistorical view of Venezuela in the work of Alexander Von Humboldt. Briceño Monzón, Claudio Alberto Rafael María Rosales y el Táchira fronterizo (apuntes para la historiografía regional venezolana). Rafael María Rosales and the Táchira borderland (notes for the Venezuelan regional historiography). Niño S., Gladys Teresa Proceso de urbanización en las áreas periféricas de la ciudad de Trujillo: micro cuenca de la quebrada El Oro. Urban process in the outskirts of Trujillo city: the basin of "El Oro" stream. Pérez Colmenares, Soraya Concentraciones de plomo en sangre y orina de trabajadores en expendios de gasolina, Trujillo- Venezuela. Lead concentration on the blood and urines of workers at petrol stations, Trujillo City, Venezuela. Aranguren Z., Freddy; Burguera, José Luis; Pascu de Burguera, Marcela y Montilla, Josefa María ¿Como estimar una función de demanda? Caso: demanda de carne de res en Colombia. How to estimate a demand function? Case: demand of cattle meat in Colombia. Caraballo, Leonardo Javier Notas y Documentos Análisis de una estabilidad numérica del esquema implícito de los cuatro puntos basado en diferencias finitas. Numerical stability analysis of the four point implicit finite differences scheme. Canelón S., Darío J. Alisdair Rogers (1997) "una cronología de la geografía 1859-1995". Alisdair Rogers (1997) "a cronology of geography 1859-1995. Rodríguez, Ingrid y Vizamón, Emmagly Bibliografía Crítica Socorro Ramírez, José María Cárdenas (2003). La vecindad colombo venezolana: Imágenes y realidades. Universidad Central de Venezuela (UCEVEN)- Universidad Nacional de Colombia (UNAL), Convenio Andrés Bello - Bogotá. Ramírez, Ricardo Índice [email protected]@[email protected]@ula.veNivel analíticosemestra

Increasing the working calibration range by means of artificial neural networks for the determination of cadmium by graphite furnace atomic absorption spectrometry

Increasing the working calibration range by means of artificial neural networks for the determination of cadmium by graphite furnace atomic absorption spectrometry (Hernández C., Edwin A.; Ávila G., Rita M.; Rivas E., Francklin I.; Burguera, Marcela y Burguera, José Luis) Abstract Feed-forward artificial neural networks (ANNs), trained with the generalized delta rule, were evaluated for modeling the non-linear behavior of calibration curves and increasing the working range for the determination of cadmium by graphite furnace atomic absorption spectrometry (GFAAS). Selection of this analyte was made on the basis of its short linear range (up to 4.0 µg l-1). Two-layer neural networks, comprising one node in the input layer (linear transfer function); a variable number of neurons in the hidden layer (sigmoid transfer functions), and a single neuron (linear transfer function) in the output layer were assessed for such a purpose. The (1:2:1) neural network was selected on the basis of its capacity to adequately model the working calibration curve in the range of study (0-22.0 µg l-1 Cd). The latter resulted in a nearly six fold increase in the working range. Cadmium was determined in the certified reference material "Trace Elements in DrinkingWater" (High Purity Standards, Lot No. 490915) at four concentration levels (2.0, 4.0, 8.0 and 12.0 µg l-1 Cd), which were experimentally within and above the linear dynamic range (LDR). No significant differences (P < 0.05) were found between the expected concentrations and the results obtained by means of the neural network. The proposed method was compared with the conventional "dilution" approach, and with fitting the working calibration curve by means of a second-order polynomial. Modeling by means of an ANN represents an alternative calibration technique, for its use helps in reducing sample manipulation (due to the extension of the working calibration range), and may provide higher accuracy of the determinations in the non-linear portion of the curve (as a result of the better fitness of the model). Artículo publicado en: Talanta 63 (2004) [email protected]@[email protected]@[email protected] monográfic

Subphrenic Abscess as a Complication of Hemodialysis Catheter-Related Infection

We describe an unusual case of subphrenic abscess complicating a central venous catheter infection caused by Pseudomonas aeruginosa in a 59-year-old woman undergoing hemodialysis. The diagnosis was made through computed tomography, and Pseudomonas aeruginosa was isolated from the purulent drainage of the subphrenic abscess, the catheter tip and exit site, and the blood culture samples. A transesophageal echocardiography showed a large tubular thrombus in superior vena cava, extending to the right atrium, but no evidence of endocarditis or other metastatic infectious foci. Catheter removal, percutaneous abscess drainage, anticoagulation, and antibiotics resulted in a favourable outcome

Distorsión del mapa enzimático renal en ratas tratadas con Menadiona (Vitamina K3)

RENOVARSE O PERECER Durante varios años hemos sido afortunados por contar con nuestra propia revista. Constituida un foro abierto para la expresión del quehacer científico y académico de nuestros compañeros universitarios, dio también cabida a la participación de importantes investigadores nacionales e internacionales que tuvieron a bien permitirnos la publicación de su valiosa producción. La responsabilidad entregada al nuevo Comité Editorial nos motiva entre otras cosas a elevar una cordial y sincera invitación a todos los miembros de la planta docente de nuestra Facultad y el resto de la Universidad, para que nos acompañen en la renovación de la Revista de la Facultad de Farmacia y Bioanálisis. Albert Einsten consideraba que el tiempo se movía inexorablemente en línea recta a través del espacio. No podemos entonces olvidar que todos viajamos adosados a él en su perenne recorrido, y que estamos obligados a mantenernos actualizados en la medida exacta a la realidad cronológica en que nos encontremos. A éste respecto, es ineludible reconocer el esfuerzo de la Prof. Patricia Vit, quien fuera miembro del Comité Editorial el hacer posible que en la actualidad nuestra producción científica sea accesible en el ciberespacio, a través de la sección de Revistas Electrónicas en el portal www.saber.ula.ve. Nuestro arribo a estos espacios virtuales amerita ampliar el horizonte de contenido científico en nuestras publicaciones. Con éste objetivo, en la actualidad nos hallamos ampliando la base de datos para el arbitraje del material a publicarse en nuestra revista y que contará con la inclusión de personajes ampliamente reconocidos en el mundo científico, tecnológico y humanístico. Su colaboración constituirá un apoyo importante en la sustentación de una base firme que permita consolidar ésta nueva etapa de la Revista de la Facultad de Farmacia. Continuemos entonces como "un solo hombre" en la forja de un nuevo esquema en la producción científica universitaria, que sea cónsona con nuestro "viaje paralelo" al tiempo y que además represente inequívocamente el poder creativo y futurista de nuestra actividad profesional. Prof. César Pérez-MaldonadoCorrelación interlaboratorio en la valoración de la expresión de Glicoproteína P en sangre periférica por citometría de flujoGuillén Ferraro, Morella; O'valle, Francisco; Olmo, A.; Aguilar, M.; Oyonarte, S.; García del Moral, RaimundoHallazgos microbiológicos cervicovaginales en pacientes de pesquisa de cáncerGuillén Ferraro, Morella; Moreno, F.; López de Sánchez, Mercedes; Omaña, T.; Altuve, F.; Toro de Méndez, MorelvaEvaluación de un medio de cultivo y la técnica de filtración para el aislamiento de Campylobacter sp. en un grupo de riesgoDíaz Ganaim, Clara; Vizcaya Delgado, Luisa; Velasco Carrillo, JudithComposición química de los aceites esenciales de Ocimum basilicum L. var basilicum, O. basilicum L. var purpurenscens, O. gratissimum L., y O. tenuiflorum L., y su efecto antimicrobiano sobre bacterias multirresistentes de origen nosocomialAcosta, María; González, María; Araque, María; Velazco, Elsa; Khouri, Nancy; Rojas, Luis; Usubillaga, AlfredoDistorsión del mapa enzimático renal en ratas tratadas con Menadiona (Vitamina K3)Alarcón Corredor, Oscar Marino; Guerrero, Ybrain; Di Bernardo, María L.; Pascu de Burguera, Marcela; Burguera, José Luis; Burguera-Pascu, Constantin R.; Alarcón Silva, Angel O.Evaluación externa de la calidad en Bioquímica Clínica en laboratorios clínicos de Cumaná - SucreGuarache, Haideé; Rodríguez, NorysValidación de la prueba de esterilidad para vacunas virales preparadas en vehículos oleoso y acuosoCortés, Alejandra; Sandino, Cecilia; Arias, JanethEfecto diferencial de la 4’-epi-doxorubicina sobre plásmido y cromosoma en aislados de enterobacterias con resistencia a antibióticos b-lactámicosLapenna M., Elisa A.; Sánchez G., Racely E.; Díaz, L. E.; Grassi, H. C.; Medina-Ramírez, Gerardo; Andrades, EdjEstandarización del método para medir el efecto diferencial de los Antibióticos Antraciclínicos (ATC) Doxorubicina y 4’epi Doxorubicina sobre plásmido y/o cromosoma bacteriano in vivoPatiño Uzcátegui, Anelvi; Colmenares, Melisa; Díaz, L. E.; Grassi, H. C.; Andrades, EdjSuperficies de respuesta de la transferencia de masa durante la deshidratación osmótica del melón (Cucumis melo, variedad Edisto)Corzo, Otoniel; Centeno, Angel E.Micropropagación del tomatillo (Physalis ixocarpa L.)Contreras G., Idel; Almeida Puentes, JhonataEstudios in vitro de los mecanismos fotooxidantes y antioxidantes de los principios activos del Aloe VeraVargas V., Franklin F.; Díaz, YreneEstudio etnobotánico de algunas plantas medicinales expendidas en los herbolarios de Mérida, Ejido y Tabay (Estado Mérida - Venezuela)Gil Otaiza, Ricardo; Mejías, Richart; Carmona Arzola, Juan; Mejías, Rafael; Rodríguez Arredondo, MaríaAnacardium occidentale L. Ficha botánica de interés apícola en Venezuela, No. 6 MereyVit Olivier, PatriciaEspeletia schultzii Wedd. Ficha botánica de interés apícola en Venezuela, No. 5 FrailejónVit Olivier, Patricia; Meléndez, Pablo; Schwartzenberg, Juan CarlosUn significado global para el científico biomédico o bioanalistaDonovan, Stephen J.; Djabayan, Pablo; Bunker, [email protected]@[email protected]@ula.veNivel analíticosemestra

Las micelas en química analítica, aplicaciones en la espectroscopia de absorción atómica

Las micelas en química analítica, aplicaciones en la espectroscopia de absorción atómica (Ávila G., Rita M.; Burguera, José Luis; Salager, Jean Louis y Bracho P., Carlos L.) Resumen En este trabajo se explican, de manera breve. varios fundamentos teóricos relacionados con las micelas, es decir. que es un surfactante, en que consisten y como se forman estas estructuras, etc. Además. se muestran algunas aplicaciones que tienen las micelas en la espectroscopia de absorción atómica (AAS). Estas se utilizan, en AAS. principalmente para cambiar algunas propiedades físicas de la muestra, e. g. viscosidad. tensión superficial. etc.. lo que puede ser empleado para optimizar la eficiencia de nebulización y mejorar la mojabilidad de superficies sólidas, entre otras. Con este trabajo no se pretende realizar una extensa revisión del tema, sino, ilustrar con ejemplos prácticos, la utilidad de estas estructuras en la mencionada área. Abstract In this work are briefly explained some theoretical foundaments related to micelles, e. g, what is a surfactant, what are micelles, and how are they formed, etc. Also, are shown some of applications of micelles in atomic absorption spectrometry (AAS), since they are mainly used to change some of the physical properties of the sample, like viscosity, surface tension, etc. Such physical-chemical modifications can be taken advantage in the improvement of various analytical systems performance by increasing the nebulizacion efficiency, improving the wettability of solid surfaces, among others. The present paper is not intended to be an extensive revision of the topic, but it is hoped that it will useful to illustrate the effectiveness of such structures in the aforementioned area. Artículo Publicado en la Revista de la Sociedad Venezolana de Química: Volumen 26 Nº 2. Abril-junio [email protected]@[email protected]@ula.veNivel monográfic

Diálisis peritoneal paliativa: implantación de un programa de atención domiciliaria a enfermos tratados con diálisis peritoneal (DP) en situación terminal

[EN]: Terminal-stage patients on peritoneal dialysis (PD) are often transferred to haemodialysis as they are unable to perform the dialysis technique themselves since their functional capacities are reduced. We present our experience with five patients on PD with a short-term life-threatening condition, whose treatment was shared by primary care units and who were treated with a PD modality adapted to their circumstances, which we call Palliative Peritoneal Dialysis. © 2015 Sociedad Española de Nefrología.[ES]: Los pacientes en Diálisis peritoneal (DP) en situación terminal suelen ser transferidos a hemodiálisis ya que son incapaces de realizarse la técnica dialítica a consecuencia de que sus capacidades funcionales están disminuidas. Presentamos nuestra experiencia con 5 pacientes en DP con patología que amenazaba su vida a corto plazo, cuyo tratamiento fue compartido por las unidades de atención primaria y fueron mantenidos en una modalidad de DP adaptada a sus circunstancias a la que hemos denominado Diálisis Peritoneal Paliativa. © 2015 Sociedad Española de Nefrología