Alineamiento múltiple de secuencias con T-Coffee: una aproximación paralela

Las aplicaciones de alineamiento múltiple de secuencias son prototipos de aplicaciones que requieren elevada potencia de cómputo y memoria. Se destacan por la relevancia científica que tienen los resultados que brindan a investigaciones científicas en el campo de la biomedicina, genética y farmacología. Las aplicaciones de alineamiento múltiple tienen la limitante de que no son capaces de procesar miles de secuencias, por lo que se hace necesario crear un modelo para resolver la problemática. Analizando el volumen de datos que se manipulan en el área de las ciencias biológica y la complejidad de los algoritmos de alineamiento de secuencias, la única vía de solución del problema es a través de la utilización de entornos de cómputo paralelos y la computación de altas prestaciones. La investigación realizada por nosotros tiene como objetivo la creación de un modelo paralelo que le permita a los algoritmos de alineamiento múltiple aumentar el número de secuencias a procesar, tratando de mantener la calidad en los resultados para garantizar la precisión científica. El modelo que proponemos emplea como base la clusterización de las secuencias de entrada utilizando criterios biológicos que permiten mantener la calidad de los resultados. Además, el modelo se enfoca en la disminución del tiempo de cómputo y consumo de memoria. Para presentar y validar el modelo utilizamos T-Coffee, como plataforma de desarrollo e investigación. El modelo propuesto pudiera ser aplicado a cualquier otro algoritmo de alineamiento múltiple de secuencias.

Ectodysplasin regulates hormone-independent mammary ductal morphogenesis via NF-κB.

Ductal growth of the mammary gland occurs in two distinct stages. The first round of branching morphogenesis occurs during embryogenesis, and the second round commences at the onset of puberty. Currently, relatively little is known about the genetic networks that control the initial phases of ductal expansion, which, unlike pubertal development, proceeds independent of hormonal input in female mice. Here we identify NF-κB downstream of the TNF-like ligand ectodysplasin (Eda) as a unique regulator of embryonic and prepubertal ductal morphogenesis. Loss of Eda, or inhibition of NF-κB, led to smaller ductal trees with fewer branches. On the other hand, overexpression of Eda caused a dramatic NF-κB-dependent phenotype in both female and male mice characterized by precocious and highly increased ductal growth and branching that correlated with enhanced cell proliferation. We have identified several putative transcriptional target genes of Eda/NF-κB, including PTHrP, Wnt10a, and Wnt10b, as well as Egf family ligands amphiregulin and epigen. We developed a mammary bud culture system that allowed us to manipulate mammary development ex vivo and found that recombinant PTHrP, Wnt3A, and Egf family ligands stimulate embryonic branching morphogenesis, suggesting that these pathways may cooperatively mediate the effects of Eda.

HTLV-I associated cutaneous T-cell lymphoma: report of a case with atypical clinical presentation

A case of a 20-years-old black man from Salvador, Bahia with HTLV-I associated T cell lymphoma is presented. In spite of the absence of splenomegaly and leukemia, the patient had a marked cephalic tumoral infiltrationassociated with axillary tumors in a pattern not yet described in adult T cell lymphoma. Peripheral blood involvement was observed later on in the course of thedisease. The patient underwent chemotherapy but died seven monts after diagnosis.

El impacto de las aplicaciones intensivas de E/S en la planificación de trabajos en clusters no-dedicados

Con la mayor capacidad de los nodos de procesamiento en relación a la potencia de cómputo, cada vez más aplicaciones intensivas de datos como las aplicaciones de la bioinformática, se llevarán a ejecutar en clusters no dedicados. Los clusters no dedicados se caracterizan por su capacidad de combinar la ejecución de aplicaciones de usuarios locales con aplicaciones, científicas o comerciales, ejecutadas en paralelo. Saber qué efecto las aplicaciones con acceso intensivo a dados producen respecto a la mezcla de otro tipo (batch, interativa, SRT, etc) en los entornos no-dedicados permite el desarrollo de políticas de planificación más eficientes. Algunas de las aplicaciones intensivas de E/S se basan en el paradigma MapReduce donde los entornos que las utilizan, como Hadoop, se ocupan de la localidad de los datos, balanceo de carga de forma automática y trabajan con sistemas de archivos distribuidos. El rendimiento de Hadoop se puede mejorar sin aumentar los costos de hardware, al sintonizar varios parámetros de configuración claves para las especificaciones del cluster, para el tamaño de los datos de entrada y para el procesamiento complejo. La sincronización de estos parámetros de sincronización puede ser demasiado compleja para el usuario y/o administrador pero procura garantizar prestaciones más adecuadas. Este trabajo propone la evaluación del impacto de las aplicaciones intensivas de E/S en la planificación de trabajos en clusters no-dedicados bajo los paradigmas MPI y Mapreduce.

MR MAQ: algorisme de Read Mapping utilitzant la plataforma Hadoop

L’èxit del Projecte Genoma Humà (PGH) l’any 2000 va fer de la “medicina personalitzada” una realitat més propera. Els descobriments del PGH han simplificat les tècniques de seqüenciació de tal manera que actualment qualsevol persona pot aconseguir la seva seqüència d’ADN complerta. La tecnologia de Read Mapping destaca en aquest tipus de tècniques i es caracteritza per manegar una gran quantitat de dades. Hadoop, el framework d’Apache per aplicacions intensives de dades sota el paradigma Map Reduce, resulta un aliat perfecte per aquest tipus de tecnologia i ha sigut l’opció escollida per a realitzar aquest projecte. Durant tot el treball es realitza l’estudi, l’anàlisi i les experimentacions necessàries per aconseguir un Algorisme Genètic innovador que utilitzi tot el potencial de Hadoop.

Programació d'aplicacions bioinformàtiques

Avui en dia la biologia aporta grans quantitats de dades que només la informàtica pot tractar. Les aplicacions bioinformàtiques són la més important eina d’anàlisi i comparació que tenim per entendre la vida i aconseguir desxifrar aquestes dades. Aquest projecte centra el seu esforç en l’estudi de les aplicacions dedicades a l’alineament de seqüències genètiques, i més concretament a dos algoritmes, basats en programació dinàmica i òptims: el Needleman&Wunsch i el Smith&Waterman. Amb l’objectiu de millorar el rendiment d’aquests algoritmes per a alineaments de seqüències grans, proposem diferents versions d’implementació. Busquem millorar rendiments en temps i espai. Per a aconseguir millorar els resultats aprofitem el paral·lelisme. Els resultats dels anàlisis de les versions els comparem per obtenir les dades necessàries per valorar cost, guany i rendiment.

Extensió de COMP Superscalar

COMPSs és un entorn de programació paral·lela desenvolupat per BSC-CNS. Aquest projecte busca estendre aquest entorn per tal de dotar-lo de funcionalitats inicialment no suportades. Aquest conjunt d’extensions radiquen principalment en la implementació de mecanismes que permetin incrementar la flexibilitat, robustesa i polivalència del sistema.

Integración de Hadoop con planificadores batch

Cada vez es mayor el número de aplicaciones desarrolladas en el ámbito científico, como en la Bioinformática o en las Geociencias, escritas bajo el modelo MapReduce, empleando herramientas de código abierto como Apache Hadoop. De la necesidad de integrar Hadoop en entornos HPC, para posibilitar la ejecutar aplicaciones desarrolladas bajo el paradigma MapReduce, nace el presente proyecto. Se analizan dos frameworks diseñados para facilitar dicha integración a los desarrolladores: HoD y myHadoop. En este proyecto se analiza, tanto las posibilidades en cuanto a entornos que ofrecen dichos frameworks para la ejecución de aplicaciones MapReduce, como el rendimiento de los clúster Hadoop generados con HoD o myHadoop respecto a un clúster Hadoop físico.

Multiple non-ossifying fibromas as a cause of pathological femoral fracture in Jaffe-Campanacci syndrome.

BACKGROUND: Jaffe-Campanacci is a rare syndrome characterised by the association of café-au-lait spots, axillary freckles, multiple non-ossifying fibromas of the long bones and jaw, as well as some features of type 1 neurofibromatosis. There are less than 30 reported cases, and a genetic profile has not yet been determined. Furthermore, it has not been clarified whether it is a subtype of type 1 neurofibromatosis or a separate syndrome. The risk of pathological fracture is over 50%, due to substantial cortical thinning of the weight-bearing bones. CASE PRESENTATION: A 17-year-old female patient, known for type 1 neurofibromatosis, presented with a low-energy distal femoral fracture due to disseminated large non-ossifying fibromas. Investigations revealed all of the distinctive signs of Jaffe-Campanacci syndrome. Both her distal femurs and proximal tibias exhibited multiple non-ossifying fibromas. The fracture was treated by open reduction and internal plate fixation. Some of the bony lesions were biopsied to confirm the diagnosis. The fracture healed eventless, as did the lesions biopsied or involved in the fracture. The other ones healed after curettage and bone grafting performed at the time of plate removal. CONCLUSION: Jaffe-Campanacci is a rare syndrome having unclear interactions with type 1 neurofibromatosis, which still needs to be characterised genetically. It is associated with a high risk of pathological fracture, due to the presence of multiple large non-ossifying fibromas of the long bones, with an expected normal healing time. Curettage and bone grafting promote healing of the lesions and should be considered to prevent pathological fracture. We agree with other authors that all patients with newly-diagnosed type 1 neurofibromatosis should undergo an osseous screening to detect disseminated non-ossifying fibromas, and evaluate the inherent risk of pathological fracture.

Effect of malaria and fever on energy metabolism in Gambian children.

The aim of the present study was to measure the changes in resting energy expenditure (REE) induced by malaria and to assess to what extent they are related to fever and nutritional status. The REE of 19 Gambian children (mean age +/- SEM, 9 +/- 1 y; weight, 24 +/- 2 kg; expected weight for height 86 +/- 1%) were measured with a hood system at repeated intervals at the onset of malaria crisis (test A), 3 to 4 d after therapy (test B), and 14 to 21 d later (test C). Axillary temperature averaged 39.2 +/- 0.1, 36.6 +/- 0.1, and 36.7 +/- 0.1 degrees C in the tests A, B, and C, respectively. REE in test A was significantly higher than REE in test B (223 +/- 10 versus 174 +/- 8 kJ/kg.d, p less than 0.0001), but in test C (169 +/- 8 kJ/kg.d), it did not differ from that observed in test B. The percentage of increase in REE was significantly correlated with the difference in axillary temperature (r = 0.46, p less than 0.05); the slope of the regression line indicated an increase of 6.9% in REE/degree C of fever. Furthermore, the individual increase in REE/degree C was correlated to the percentage of weight for height of the children (r = 0.54, p less than 0.05), indicating that the child's nutritional status influences the magnitude of the hypermetabolism due to fever. We concluded that Gambian children suffering from an acute episode of malaria have an increase in REE averaging 30%; however, REE promptly returns to baseline value a few days after the beginning of therapy.

Transferrin uptake may occur through detergent-resistant membrane domains at the cytopharynx of Trypanosoma cruzi epimastigote forms

Uptake of transferrin by epimastigote forms of the protozoan Trypanosoma cruzi occurs mainly through a cytostome/ cytopharynx, via uncoated endocytic vesicles that bud off from the bottom of the cytopharynx. We have here examined whether detergent-resistant membrane (DRM) domains might be involved in this process. Purified whole cell membrane fractions were assayed for cholesterol levels and used in dot blot analyses. Detergent-resistant membrane markers (cholera B toxin and anti-flotillin-1 antibody) presented positive reaction by dot blots in cholesterol-rich/ protein-poor membrane sub-fractions. The positive dot blot fraction was submitted to lipid composition analysis, showing composition similar to that of raft fractions described for other eukaryotic cells. Immunofluorescence assays allowed the localization of punctual positive signal for flotillin-1, matching the precise cytostome/ cytopharynx location. These data were confirmed by immunofluorescence assays with the co-localization of flotillin-1 and the transferrin uptake site. Our data suggest that DRM domains occur and are integrated at the cytostome/ cytopharynx of T. cruzi epimastigotes, being the main route for transferrin uptake.

Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer.

BACKGROUND Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. METHODS After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. RESULTS Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. CONCLUSIONS Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.

The cervico-thoracic outlet compression syndrome. Analysis of surgical treatment.

Surgical treatment of the thoracic outlet compression syndrome is being presently reconsidered. Until these last few years, there was the choice between two interventions only: scalenotomy, a simple operation entailing no complication, but with a 60% recurrence rate--or the resection of the first rib through an axillary approach, an efficacious intervention which caused, however, serious nervous complications in 14% of treated cases. The follow-up of 75 cases operated for a TOCS reveals to the authors that--all techniques taken into account--results are unsatisfactory in 33% of cases. These failures are due either to technical deficiencies, or to a complication arising in the course of the operation, or to an erroneous diagnosis. The authors resort to surgery only to treat serious vascular syndromes (absolute indication) or invalidating neurological compression syndromes, after failure of physical therapy (relative indication). They propose a cervical approach--the only one enabling a safe dissection of the brachial plexus--a partial scalenectomy, resection of all fibrous bands pressing on nervous trunks, or the resection of a cervical rib. Should the costo-clavicular space appear anatomically too narrow, the first rib, already partially freed by the cervical approach, will be resected through the axillary route.

A qualidade de vida na concepção de um grupo de professoras de enfermagem: elementos para reflexão

Trata-se de um estudo qualitativo realizado a partir do conceito de qualidade de vida adotado por MEEBERG (1993) relacionado com a opinião de um grupo de professoras de enfermagem. Observou-se que este conceito está presente na fala das entrevistadas de forma bem clara, especialmente nos atributos relacionados a satisfação com a própria vida em geral e com o estado aceitável de saúde física, mental, social e emocional.

Role of estrogen receptor signaling in mammary gland development

Abstract : Breast cancer incidence rates have increased over the past hundred years, in particular, in Western industrial countries and they continue to rise worldwide. Breast cancer risk has been linked to life exposure to endogenous and exogenous estrogens, and there is increasing concern that exposure to endocrine disruptors which are increasingly accumulating in our environment may also have a role. Using the mouse as model, I have analyzed the physiological role of estrogen signaling in mammary gland development. I have shown that estrogen signaling through the estrogen receptor alpha (ERα) in the mammary epithelium is required for ductal morphogenesis during puberty. Moreover, I have demonstrated that estrogens induce proliferation of mammary epithelial cells through a paracrine mechanism. The presence of estrogen signaling is essential cell intrinsically via ERα or ERβ for the terminal differentiation into milk secreting cells during pregnancy. Furthermore, I have examined how perinatal exposure to the estrogenic plasticizer bisphenol A (BPA) found ubiquitously in consumer goods such as baby bottles formula and beverage containers affects the normal mammary gland development and possibly predispose the mammary gland to tumorigenesis. I have found that C57b16 mice that were exposed, via their drinking water, to several BPA doses ranging from 0.025µg/kg/day to 250µg/kg/day exhibits delayed terminal end bud formation and consequently the ductal outgrowth. Later in life, the mice that were exposed in utero to BPA displayed an increased number of mammary epithelial cells. Acute exposure of 3-week-old mice to BPA can alter gene expression levels of an important estrogen target gene, amphiregulin. Taken together these data are compatible with a scenario in which perinatal BPA exposure may alter mammary gland development by affecting developmental signaling pathways. Résumé : Les taux d'incidence des cancers du sein ont augmenté au cours des cent dernières années en particulier dans les pays industriels occidentaux et ils continuent d'augmenter dans le monde entier. Le risque du cancer du sein a été corrélé à l'exposition au cours de la vie aux oestrogènes endogènes et exogènes. Il y a une préoccupation croissante concernant l'exposition aux perturbateurs endocriniens qui ne cessent de s'accumulent dans notre environnement et qui peuvent également avoir un rôle dans l'augmentation des cancers du sein. En utilisant le modèle de souris, j'ai analysé le rôle physiologique de la voie de signalisation à l'oestrogène dans le développement mammaire. J'ai prouvé que l'oestrogène par l'intermédiaire de son récepteur alpha (ERα) est indispensable dans l'épithélium pour la morphogénèse du système canalaire pendant la puberté. De plus, j'ai démontré que les oestrogènes induisent la prolifération des cellules épithéliales mammaires par un mécanisme paracrine. La présence de la voie de signalisation à l'oestrogène est essentielle de manière intrinsèque à la cellule par l'intermédiaire d'ERα ou ERβ pour la différentiation terminale des cellules épithéliales en cellules sécrétrices de lait pendant la grossesse. En outre, j'ai examiné comment l'exposition périnatale au bisphénol A (BPA), un plastifiant présentant des propriétés ostrogéniques et omniprésent dans divers produits d'usage courant tels que les biberons des bébés et les récipients en plastique, affecte le développement de la glande mammaire et prédispose probablement celle-ci à la tumorigénèse. J'ai constaté que l'exposition périnatale à BPA retarde la formation des bourgeons terminaux et par conséquent la croissance du système canalaire. Plus tard dans la vie, les souris qui ont été exposées dans l'utérus au BPA ont montré un plus grand nombre de cellules épithéliales mammaires. L'exposition aiguë de souris âgées de 3 semaines au BPA perturbe le niveau d'expression d'un gène cible important de l'oestrogène, l'amphiregulin. Ces données sont compatibles avec un scénario dans lequel l'exposition périnatale au BPA peut changer le développement de la glande mammaire en affectant des voies de signalisation développementales.