Mir-190b negatively contributes to the Trypanosoma cruzi- infected cell survival by repressing PTEN protein expression

Chagas disease, which is caused by the intracellular protozoanTrypanosoma cruzi, is a serious health problem in Latin America. The heart is one of the major organs affected by this parasitic infection. The pathogenesis of tissue remodelling, particularly regarding cardiomyocyte behaviour after parasite infection, and the molecular mechanisms that occur immediately following parasite entry into host cells are not yet completely understood. Previous studies have reported that the establishment of parasitism is connected to the activation of the phosphatidylinositol-3 kinase (PI3K), which controls important steps in cellular metabolism by regulating the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate. Particularly, the tumour suppressor PTEN is a negative regulator of PI3K signalling. However, mechanistic details of the modulatory activity of PTEN on Chagas disease have not been elucidated. To address this question, H9c2 cells were infected with T. cruzi Berenice 62 strain and the expression of a specific set of microRNAs (miRNAs) were investigated. Our cellular model demonstrated that miRNA-190b is correlated to the decrease of cellular viability rates by negatively modulating PTEN protein expression in T. cruzi-infected cells.

A combined molecular clinical predictor of survival validated with the rtog-0525 cohort

For glioblastoma (GBM), survival classification has primarily relied on clinical criteria, exemplified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA). We sought to improve tumor classification by combining tumor biomarkers with the clinical RPA data. To accomplish this, we first developed 4 molecular biomarkers derived from gene expression profiling, a glioma CpG island methylator phenotype, a novel MGMT promoter methylation assay, and IDH1 mutations. A molecular predictor (MP) model was created with these 4 biomarkers on a training set of 220 retrospectively collected archival GBMtumors. ThisMPwas further combined with RPA classification to develop a molecular-clinical predictor (MCP). The median survivals for the combined, 4-class MCP were 65 months, 31 months, 13 months, and 9 months, which was significantly improved when compared with the RPA alone. The MCP was then applied to 725 samples from the RTOG-0525 cohort, showing median survival for each risk group of NR, 26 months, 16 months, and 11 months. The MCP was significantly improved over the RPA at outcome prediction in the RTOG 0525 cohort with a 33%increase in explained variation with respect to survival, validating the result obtained in the training set. To illustrate the benefit of the MCP for patient stratification, we examined progression-free survival (PFS) for patients receiving standard-dose temozolomide (SD-TMZ) vs. dose-dense TMZ (DD-TMZ) in RPA and MCP risk groups. A significant difference between DD-TMZ and SD-TMZ was observed in the poorest surviving MCP risk group with a median PFS of 6 months vs. 3 months (p ¼ 0.048, log-rank test). This difference was not seen using the RPA classification alone. In summary, we have developed a combined molecular-clinical predictor that appears to improve outcome prediction when compared with clinical variables alone. This MCP may serve to better identify patients requiring intensive treatments beyond the standard of care.

Predicting response and survival in chemotherapy-treated triple-negative breast cancer.

BACKGROUND In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). METHODS Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. RESULTS Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. CONCLUSIONS The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.

Valoración del perfil lipídico y de la densidad mineral ósea en pacientes trasplantados renales

INTRODUCTION: Alterations in lipid metabolism and bone mineral metabolism disturbances are common disorders among renal transplant patients, contributing to the apparition of oxidative metabolic and cardiovascular diseases that threaten the integrity of the graft. AIMS: Describe and observe the evolution of alterations in bone mineral density (BMD) and lipid abnormalities in a population of kidney transplant patients. MATERIAL AND METHOD: The samples consisted of 119 kidney transplant patients of both sexes, measurements were performed pretransplant and posttransplant for five years of biochemical parameters, anthropometric measurements and measurement of bone mineral density at the lumbar spine, femur and radioulnar. RESULTS: During the five years after transplantation a significant increase in biochemical parameters, BMI, dyslipidemia, diabetes and hypertension occurs. At six months there is a high percentage of patients with pathologic BMD increase by 4.1% per year of transplantation. CONCLUSIONS: After kidney transplantation, a large increase of hyperlipidemia associated with a characteristic pattern of altered lipid with elevated total cholesterol, low density lipoprotein, high density lipoprotein, and the resulting increase in triglycerides, occurs despite statin therapy, leading to an increase in risk factors for diabetes, hypertension, diseases and cardiovascualres further loss of bone mass which carries a high risk of serious fractures occurs, threatening kidney graft and quality of life of patients.

Migrador de framework SEA a JSF 2.0

Implementació d'un projecte per migrar un framework basat en Struts 1.1 a JSF 2.0, incloent les biblioteques de tags.

Uncorrelatedness in growing networks with preferential survival of nodes

The emergence of uncorrelated growing networks is proved when nodes are removed either uniformly or under the preferential survival rule recently observed in the World Wide Web evolution. To this aim, the rate equation for the joint probability of degrees is derived, and stationary symmetrical solutions are obtained, by passing to the continuum limit. When a uniformly random removal of extant nodes and linear preferential attachment of new nodes are at work, we prove that the only stationary solution corresponds to uncorrelated networks for any removal rate r ∈ (0,1). In the more general case of preferential survival of nodes, uncorrelated solutions are also obtained. These results generalize the uncorrelatedness displayed by the (undirected) Barab´asi-Albert network model to models with uniformly random and selective (against low degrees) removal of nodes

Effect of Temperature on the Development and Survival of the Argentine Ant, Linepithema humile

The influence of temperature on the developmental times and survival of insects can largely determine their distribution. For invasive species, like the Argentine ant, Linepithema humile Mayr (Hymenoptera: Formicidae), these data are essential for predicting their potential range based on mechanistic models. In the case of this species, such data are too scarce and incomplete to make accurate predictions based on its physiological needs. This research provides comprehensive new data about brood survival and developmental times at a wide range of temperatures under laboratory conditions. Temperature affected both the complete brood development from egg to adult worker and each of the immature stages separately. The higher the temperature, the shorter the development times. Brood survival from egg to adult was low, with the maximum survival rate being only 16% at 26° C. Temperature also affected survival of each of the immature stages differently: eggs were negatively affected by high temperatures, while larvae were negatively affected by low temperatures, and the survival of pupae was apparently independent of environmental temperature. At 32° C no eggs survived, while at 18° C less than 2% of the eggs hatched into larva. The data from the present study are essential for developing prediction models about the distribution range of this tramp species based on its physiological needs in relation to temperature

Release of macrophage migration inhibitory factor by neuroendocrine-differentiated LNCaP cells sustains the proliferation and survival of prostate cancer cells.

The acquisition of neuroendocrine (NE) characteristics by prostate cancer (PCa) cells is closely related to tumour progression and hormone resistance. The mechanisms by which NE cells influence PCa growth and progression are not fully understood. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in oncogenic processes, and MIF serum levels correlate with aggressiveness of PCa. Here, we investigated the regulation and the functional consequences of MIF expression during NE transdifferentiation of PCa cells. NE differentiation (NED) of LNCaP cells, initiated either by increasing intracellular levels of cAMP or by culturing cells in an androgen-depleted medium, was associated with markedly increased MIF release. Yet, intracellular MIF protein and mRNA levels and MIF gene promoter activity decreased during NED of LNCaP cells, suggesting that NED favours MIF release despite decreasing MIF synthesis. Adenoviral-mediated forced MIF expression in NE-differentiated LNCaP cells increased cell proliferation without affecting the expression of NE markers. Addition of exogenous recombinant MIF to LNCaP and PC-3 cells stimulated the AKT and ERK1/2 signalling pathways, the expression of genes involved in PCa, as well as proliferation and resistance to paclitaxel and thapsigargin-induced apoptosis. Altogether, these data provide evidence that increased MIF release during NED in PCa may facilitate cancer progression or recurrence, especially following androgen deprivation. Thus, MIF could represent an attractive target for PCa therapy.

Estudio genetico de la osteoporosis: heredabilidad de las propiedades densitométricas, estructurales y de resistencia ósea y distribución fenotípica familiar.

La base genética de la osteoporosis primaria es compleja. Involucra a múltiples genes y factores ambientales que actúan de manera conjunta para determinar el riesgo. Actualmente disponemos de exploraciones genómicas, como el estudio de miRNA, que facilitan la identificación de los determinantes genéticos de las enfermedades poligénicas complejas. Presentamos un estudio prospectivo realizado en familias con genealogia extensa para estudiar e identificar la heredabilidad de las propiedades densitométricas, estructurales y de resistencia ósea con el fin de profundizar en el conocimiento de las bases genéticas de la osteoporosis.

Effects of the social environment on the survival and fungal resistance of ant brood

The phenotype of social animals can be influenced by genetic, maternal and environmental effects, which include social interactions during development. In social insects, the social environment and genetic origin of brood can each influence a whole suite of traits, from individual size to caste differentiation. Here, we investigate to which degree the social environment during development affects the survival and fungal resistance of ant brood of known maternal origin. We manipulated one component of the social environment, the worker/brood ratio, of brood originating from single queens of Formica selysi. We monitored the survival of brood and measured the head size and ability to resist the entomopathogenic fungus Beauveria bassiana of the resulting callow workers. The worker/brood ratio and origin of eggs affected the survival and maturation time of the brood and the size of the resulting callow workers. The survival of the callow workers varied greatly according to their origin, both in controls and when challenged with B. bassiana. However, there was no interaction between the fungal challenge and either the worker/brood ratio or origin of eggs, suggesting that these factors did not affect parasite resistance in the conditions tested. Overall, the social conditions during brood rearing and the origin of eggs had a strong impact on brood traits that are important for fitness. We detected a surprisingly large amount of variation among queens in the survival of their brood reared in standard queenless conditions, which calls for further studies on genetic, maternal and social effects influencing brood development in the social insects.

Prolonged survival for patients with newly diagnosed, inoperable glioblastoma with 3-times daily ultrafractionated radiation therapy.

Ultrafractionation of radiation therapy is a novel regimen consisting of irradiating tumors several times daily, delivering low doses (<0.75 Gy) at which hyperradiosensitivity occurs. We recently demonstrated the high efficiency of ultrafractionated radiotherapy (RT) on glioma xenografts and report here on a phase II clinical trial to determine the safety, tolerability, and efficacy of an ultrafractionation regimen in patients with newly and inoperable glioblastoma (GBM). Thirty-one patients with histologically proven, newly diagnosed, and unresectable supratentorial GBM (WHO grade IV) were enrolled. Three daily doses of 0.75 Gy were delivered at least 4 hours apart, 5 days per week over 6-7 consecutive weeks (90 fractions for a total of 67.5 Gy). Conformal irradiation included the tumor bulk with a margin of 2.5 cm. The primary end points were safety, toxicity, and tolerability, and the secondary end points were overall survival (OS) and progression-free survival (PFS). Multivariate analysis was used to compare the OS and PFS with the EORTC-NCIC trial 26981-22981/CE.3 of RT alone vs radiation therapy and temozolomide (TMZ). The ultrafractionation radiation regimen was safe and well tolerated. No acute Grade III and/or IV CNS toxicity was observed. Median PFS and OS from initial diagnosis were 5.1 and 9.5 months, respectively. When comparing with the EORTC/NCIC trial, in both PFS and OS multivariate analysis, ultrafractionation showed superiority over RT alone, but not over RT and TMZ. The ultrafractionation regimen is safe and may prolong the survival of patients with GBM. Further investigation is warranted and a trial associating ultra-fractionation and TMZ is ongoing.

Genetic structure of a linear population of Beta vulgaris ssp maritima (sea beet) revealed by isozyme and RFLP analysis

Knowledge of the genetic structure of plant populations is necessary for the understanding of the dynamics of major ecological processes. It also has applications in conservation biology and risk assessment for genetically modified crops. This paper reports the genetic structure of a linear population of sea beet, Beta vulgaris ssp. maritima (the wild relative of sugar beet), on Furzey Island, Poole Harbour. The relative spatial positions of the plants were accurately mapped and the plants were scored for variation at isozyme and RFLP loci. Structure was analysed by repeated subdivision of the population to find the average size of a randomly mating group. Estimates of F-ST between randomly mating units were then made, and gave patterns consistent with the structure of the population being determined largely by founder effects. The implications of these results for the monitoring of transgene spread in wild sea beet populations are discussed.