RNAiFold2T: Constraint Programming design of thermo-IRES switches

Motivation: RNA thermometers (RNATs) are cis-regulatory ele- ments that change secondary structure upon temperature shift. Often involved in the regulation of heat shock, cold shock and virulence genes, RNATs constitute an interesting potential resource in synthetic biology, where engineered RNATs could prove to be useful tools in biosensors and conditional gene regulation. Results: Solving the 2-temperature inverse folding problem is critical for RNAT engineering. Here we introduce RNAiFold2T, the first Constraint Programming (CP) and Large Neighborhood Search (LNS) algorithms to solve this problem. Benchmarking tests of RNAiFold2T against existent programs (adaptive walk and genetic algorithm) inverse folding show that our software generates two orders of magnitude more solutions, thus allow- ing ample exploration of the space of solutions. Subsequently, solutions can be prioritized by computing various measures, including probability of target structure in the ensemble, melting temperature, etc. Using this strategy, we rationally designed two thermosensor internal ribosome entry site (thermo-IRES) elements, whose normalized cap-independent transla- tion efficiency is approximately 50% greater at 42?C than 30?C, when tested in reticulocyte lysates. Translation efficiency is lower than that of the wild-type IRES element, which on the other hand is fully resistant to temperature shift-up. This appears to be the first purely computational design of functional RNA thermoswitches, and certainly the first purely computational design of functional thermo-IRES elements. Availability: RNAiFold2T is publicly available as as part of the new re- lease RNAiFold3.0 at https://github.com/clotelab/RNAiFold and http: //bioinformatics.bc.edu/clotelab/RNAiFold, which latter has a web server as well. The software is written in C++ and uses OR-Tools CP search engine.Comment: 24 pages, 5 figures, Intelligent Systems for Molecular Biology (ISMB 2016), to appear in journal Bioinformatics 201

The macrofilaricidal efficacy of repeated doses of ivermectin for the treatment of river blindness

Background: Mass drug administration (MDA) with ivermectin is the cornerstone of efforts to eliminate human onchocerciasis by 2020 or 2025. The feasibility of elimination crucially depends on the effects of multiple ivermectin doses on Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the release of such progeny by female macrofilariae, but a macrofilaricidal effect has been deemed minimal. Multiple doses of ivermectin may cumulatively and permanently reduce the fertility and shorten the lifespan of adult females. However, rigorous quantification of these effects necessitates interrogating longitudinal data on macrofilariae with suitably powerful analytical techniques. Methods: Using a novel mathematical modeling approach, we analyzed, at an individual participant level, longitudinal data on viability and fertility of female worms from the single most comprehensive multiple-dose clinical trial of ivermectin, comparing 3-monthly with annual treatments administered for 3 years in Cameroon

A mindfulness and compassion-based program applied to pregnant women and their partners to decrease depression symptoms during pregnancy and postpartum: Study protocol for a randomized controlled trial

Background: Pregnancy and the postpartum period are times of great change for women and their partners, often bringing substantial challenges and stress. Approximately 10%-20% of women suffer from mood disorders such as depression in the perinatal period. There are risks involved in using psychopharmacological interventions to treat perinatal depression. Mindfulness and compassion-based educational programs could be efficacious and cost-effective options for the prevention and treatment of perinatal mood disorders. The aim of this study is to assess the efficacy of an adapted Mindfulness-Based Childbirth and Parenting (MBCP) program that includes compassion training for pregnant women in primary care (PC) settings in the Spanish National Health System to decrease perinatal depression. Methods: A multicenter randomized controlled trial (RCT) will be conducted. Participants will be pregnant women (n = 122) and their partners who wish to participate. They will be enrolled and assessed in PC settings and randomly assigned to either: (1) an adapted MBCP educational program tailored to the Spanish National Health System + treatment as usual (TAU); or (2) TAU only. The main outcome to be assessed will be depression, evaluated with the Edinburgh Postnatal Depression Scale (EPDS). Secondary outcomes will include self-reported measures of perceived stress, affects, mindfulness, self-compassion, maternal self-efficacy, and use of health and social services. Patients will be assessed at four timepoints: baseline; post-treatment; and at three and six months after childbirth. Intention-to-treat and per-protocol analyses will be carried out using linear regression mixed models. Effect sizes will be estimated using Cohen''s d. Discussion: Perinatal depression is a significant health problem. An effective and low-cost childbirth education program that incorporates mindfulness and compassion practices may be a beneficial preventive complementary healthcare modality for expectant women and their partners. This study will be the first multicenter RCT in Spanish PC settings using adapted MBCP and compassion practices to reduce symptoms of depression during pregnancy and the postpartum period

ICF-Based Disability Survey in a Rural Population of Adults and Older Adults Living in Cinco Villas, Northeastern Spain: Design, Methods and Population Characteristics

Background: This article describes the methods of a door-to-door screening survey exploring the distribution of disability and its major determinants in northeastern Spain. This study will set the basis for the development of disability-related services for the rural elderly in northeastern Spain. Methods: The probabilistic sample was composed of 1,354 de facto residents from a population of 12,784 Social Security card holders (age: 6 50 years). Cognitive and disability screenings were conducted (period: June 2008-June 2009). Screening instruments were the MMSE and the World Health Organization Disability Assessment Schedule. Participants screened positive for disability underwent an assessment protocol focusing on primary care diagnoses, disability, lifestyle, and social and health service usage. Participants screened positive for cognitive functioning went through in-depth neurological evaluation. Results: The study sample is described. Usable data were available for 1,216 participants. A total of 625 individuals (51.4%) scored within the positive range in the disability screening, while 135 (11.1%) scored within the positive range of the cognitive screening. The proportion of positively screened individuals was higher for women and increased with age. Conclusions: Screening surveys represent a feasible design for examining the distribution of disability and its determinants among the elderly. Data quality may benefit from methodological developments tailored to rural populations with a low education level. Copyright (C) 2010 S. Karger AG, Base

Anti-CD44-Conjugated Olive Oil Liquid Nanocapsules for Targeting Pancreatic Cancer Stem Cells

The latest trends in cancer research and nanomedicine focus on using nanocarriers to target cancer stem cells (CSCs). Specifically, lipid liquid nanocapsules are usually developed as nanocarriers for lipophilic drug delivery. Here, we developed olive oil liquid NCs (O2LNCs) functionalized by covalent coupling of an anti-CD44-fluorescein isothiocyanate antibody ({\alpha}CD44). First, O2LNCs are formed by a core of olive oil surrounded by a shell containing phospholipids, a nonionic surfactant, and deoxycholic acid molecules. Then, O2LNCs were coated with an {\alpha}CD44 antibody ({\alpha}CD44-O2LNC). The optimization of an {\alpha}CD44 coating procedure, a complete physicochemical characterization, as well as clear evidence of their efficacy in vitro and in vivo were demonstrated. Our results indicate the high targeted uptake of these {\alpha}CD44-O2LNCs, and the increased antitumor efficacy (up to four times) of paclitaxel-loaded-{\alpha}CD44-O2LNC compared to free paclitaxel in pancreatic CSCs (PCSCs). Also, {\alpha}CD44-O2LNCs were able to selectively target PCSCs in an orthotopic xenotransplant in vivo model.Comment: 16 pages, 4 figures, 1 tabl

Plan de negocios para evaluar la viabilidad econ?mica de una empresa dedicada a la comercializaci?n de potenciadores de sabor l?quido para agua enfocada en el canal moderno

El mercado mundial de los potenciadores de sabor l?quido para agua est? experimentando un crecimiento prometedor, debido a la creciente popularidad de que, al combinarlo con agua, ofrecen una hidrataci?n saludable. Los potenciadores de sabor l?quido, son formulaciones concentradas que se comercializan en deliciosos sabores en Estados Unidos y Europa. De acuerdo con la investigaci?n realizada, estos productos no se comercializan en el mercado local. Por otro lado, estos productos no contienen az?car y supone una ingesta cero calor?as. Es as?, que nace ?Funny Drops?, como una oportunidad para crear una nueva categor?a de productos y lanzarlo al mercado a trav?s del canal moderno. Por ello, la presente tesis tiene como objetivo general demostrar mediante la evaluaci?n econ?mica, la factibilidad de comercializar los potenciadores de sabor l?quido en el canal moderno. Para cumplir con el objetivo general del proyecto, se realizaron 7 entrevistas a expertos en el sector y 384 encuestas para demostrar la existencia de la oportunidad de lanzar al mercado peruano una marca de potenciadores de sabor l?quido para agua. De esa manera, nos ha permitido validar la propuesta de valor del producto y tambi?n poder definir los siguientes planes: estrat?gico, marketing, operaciones, recursos humanos y tecnolog?a de informaci?n. Los potenciadores de sabor l?quido que se pretenden comercializar est?n dirigidos a hombres y mujeres de 25 a 40 a?os de los niveles socioecon?micos A y B. Como objetivos a corto plazo se pretende conseguir una cuota de mercado de 3.54% para el primer a?o y 12% hacia el quinto a?o. Por otro lado, conforme con la evaluaci?n financiera realizada con proyecci?n a 5 a?os, indican que se obtiene como resultado un VAN de S/1,069,092 y un TIR de 42.76%. La producci?n de los potenciadores de sabor l?quido, se proyecta fabricarlo en una planta de m?s de 1000 metros cuadrados, ubicado en el distrito de Ate. Asimismo, el precio del producto ser? establecido en S/17.50 de venta al p?blico y tendr? una presentaci?n de 48 mililitros, que rinde 24 servidas. Los deliciosos sabores que inicialmente se van a ofrecer son: limonada, fresa y maracuy?

ID1 and ID4 Are Biomarkers of Tumor Aggressiveness and Poor Outcome in Immunophenotypes of Breast Cancer

Inhibitor of differentiation (ID) proteins are a family of transcription factors that contribute to maintaining proliferation during embryogenesis as they avoid cell differentiation. Afterward, their expression is mainly silenced, but their reactivation and contribution to tumor development have been suggested. In breast cancer (BC), the overexpression of ID1 has been previously described. However, whether the remaining ID genes have a specific role in this neoplasia is still unclear. We studied the mRNA expression of all ID genes by q RT-PCR in BC cell lines and 307 breast carcinomas, including all BC subtypes. Our results showed that ID genes are highly expressed in all cell lines tested. However, ID4 presented higher expression in BC cell lines compared to a healthy breast epithelium cell line. In accordance, ID1 and ID4 were predominantly overexpressed in Triple-Negative and HER2-enriched samples. Moreover, high levels of both genes were associated with larger tumor size, histological grade 3, necrosis and vascular invasion, and poorer patients’ outcomes. In conclusion, ID1 and ID4 may act as biomarkers of tumor aggressiveness and worse prognosis in breast cancer, and they could be used as potential targets for new treatments discover.This research was funded by the Alicante Institute for Health and Biomedical Research (ISABIAL) (UGP 16-149 and UGP 180184) and Navarro-Tripodi Foundation (BOLA00150). M.G.E. was supported by fellowships issued by the Valencian Government of Spain (GVA) and the European Social Fund (ACIF/2016/004)

La intensificación sustentable de la producción, los servicios ecosistémicos y los cultivos de cobertura

La intensificación sustentable de la agricultura plantea la producción de los cultivos haciendo un uso eficiente de los recursos naturales e insumos, con el menor impacto ambiental sobre los agroecosistemas, manteniendo la biodiversidad, conservando los recursos naturales, reduciendo los procesos de contaminación y favoreciendo el desarrollo local de las comunidades.EEA OliverosFil: Bacigaluppo, Silvina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Enrico, Juan Martin. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Estancich, Evangelina Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Garcia, Andrea Veronica. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Kehoe, Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Lago, Maria Elena. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Papa, Juan Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; Argentina.Fil: Rotolo, Gloria Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; Argentina.Fil: Sanmarti, Nicolas. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Salvagiotti, Fernando. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; Argentin

Analysis of urinary exosomal metabolites identifies cardiovascular risk signatures with added value to urine analysis

Background: Subclinical atherosclerosis may result in fatal cardiovascular (CV) events, but the underlying mechanisms and molecular players leading to disease are not entirely understood. Thus, novel approaches capable of identifying the factors involved in pathological progression and providing a better understanding of the subjacent mechanisms are needed. Extracellular vesicles (EVs) have been shown to have numerous biological functions, and their metabolome has recently generated interest as a source of novel biomarkers. The metabolic content of the exosomes has been so far unexplored in cardiovascular disease (CVD), and here, we developed an analytical strategy aimed at probing urinary exosomal metabolite content and its association to CV risk. Results: Direct analysis of the exosomes without metabolite extraction was evaluated by high-resolution magic angle spinning (1 H HR-MAS). Other two methodologies for the analysis of exosomal metabolites by 1 H NMR were set up, based on methanol or organic solvents sequential extraction. The three methods were compared in terms of the number of detected signals and signal to noise ratio (S/N). The methanol method was applied to identify altered metabolites in the urinary exosomes of subjects with programmed coronary artery by-pass grafting (CABG) versus a control group. Target mass spectrometry (MS) was also performed for differential analysis. The clinical performance of exosomal metabolites of interest in CVD was investigated, and the added value of the exosomes compared to urine analysis was evaluated. Based on S/N ratio, simplicity, reproducibility, and quality of the spectrum, the methanol method was chosen for the study in CVD. A cardiometabolic signature composed by 4-aminohippuric acid, N-1-methylnicotinamide, and citric acid was identified in urinary exosomes. Directly in urine, 4-aminohippuric acid and citric acid do not show variation between groups and changes in N-1-methylnicotinamide are less pronounced, proving the added value of exosomes. Conclusions: We set up a novel methodology to analyze metabolic alterations in urinary exosomes and identified a cardiometabolic signature in these microvesicles. This study constitutes the first evidence of a role for the exosomal metabolism in CVD and demonstrates the possibility to evaluate the urinary exosomal metabolic content by NMR and MS

Real-world evidence of brexucabtagene autoleucel for the treatment of relapsed or refractory mantle cell lymphoma

Altres ajuts: Beca PERIS 2018-2020 de la Generalitat de Catalunya (BDNS357800