Diagnóstico de áreas degradadas ripárias no Rio São Francisco: criação e utilização de banco de dados relacional.

Para compor um programa de recuperação de ambientes ripários no Semiárido, diagnósticos foram realizados com a finalidade de embasar planos de manejo. Contudo, as variáveis utilizadas por cada área de estudo acumulavam-se em um grande número de dados e informações, tornando o diagnóstico de difícil entendimento, por dificuldades de se relacionarem todos os dados coletados. Assim, o objetivo deste trabalho foi criar um banco de dados relacional para a manipulação de todos os dados e informações referentes ao diagnóstico de áreas degradadas ciliares do Rio São Francisco na RIDE de Petrolina?Juazeiro. Para a construção do sistema de banco de dados relacional utilizou-se a ferramenta MySQL. Esse sistema possibilita ter vários usuários, com acesso de diferentes locais. As tabelas de dados foram trabalhadas nos editores de planilhas BrOffice Calc ou Excel. O software (interface) utilizado para dar acesso, exportação e importação dos dados foi o phpMyadmin. Após a criação e utilização do banco de dados, constatou-se que o banco de dados desenvolvido atende a necessidade de pesquisa relacional, uma vez que permite utilizar um número de identificação (ID), de fácil acesso e manipulação, gerado a partir do estabelecimento de relações entre as variáveis analisadas

Efecto del gen BMP15 sobre la distribución del tipo de parto en ovejas Rasa Aragonesa

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Relationship between the effects of the BMP15 gene and the polygenic effects on prolificacy in the rasa Aragonesa sheep breed

Los efectos del gen BMP15, localizado en el cromosoma X, sobre la media y la variabilidad de la prolificidad fueron estimados en la población Rasa Aragonesa, donde se analizaron 918.956 partos de ovejas de distintos genotipos (heterocigotas para el alelo FecXR o ROA®; y no portadoras). En primer lugar, se utilizaron modelos umbral que incluían o no el efecto del gen para estimar el efecto del genotipo BMP15 y su contribución a la variabilidad genética de la prolificidad en esta población. También se utilizaron otros dos modelos para estimar las interacciones entre el genotipo y los poligenes, así como el efecto del genotipo sobre la variabilidad de la prolificidad. Todos los análisis se hicieron con el programa ASReml. El efecto del genotipo sobre la media fue de 0,32 corderos adicionales por parto cuando el alelo ROA® se encontraba presente. Debido a que durante muchos años la selección por prolificidad en esta población se ha llevado a cabo desconociendo la presencia de esta mutación, los animales selectos portadores tienen un valor genético poligénico residual más bajo que los no portadores. No se encontró interacción significativa entre el genotipo y los efectos poligénicos sobre el valor genético. Aunque la interacción entre el genotipo y el conjunto de umbrales fue significativa, la diferencia entre ambos genotipos en la varianza de la prolificidad sobre la escala observada a una prolificidad media dada es escasa y muy poco relevanteThe effects of the BMP15 gene, located on the X chromosome, on mean prolificacy and its variability, were estimated in the Rasa Aragonesa sheep population through the analysis of 918,956 lambing records from ewes of different genotypes (FecXR or ROA® heterozygous ewes; and non-carrier ewes). Threshold models including or not the gene effect were first run to determine the effect of the BMP15 genotype and its importance in the total genetic variability of prolificacy. Two other models were also run to estimate the interaction between the BMP15 genotype and the polygenic background, as well as the effect of the genotype on the variability prolificacy. All the models were run using the ASReml software. The effect of the presence of the ROA® allele of the BMP15 gene on the mean prolificacy was 0.32 extra lambs per lambing. Due to the selection on prolificacy performed during many years in this population ignoring the presence of this major gene, animals carrying the mutation were found to have lower remaining polygenic estimated breeding values than non-carrier animals, and there was no interaction between the BMP15 genotype and the polygenic background. Although the interaction between the genotype and the set of thresholds was significant, the resulting between-genotypes difference of variance of prolificacy on the observed scale, at a similar mean litter size, was very low and not relevantPublishe

Dark matter line searches with the Cherenkov Telescope Array

Monochromatic gamma-ray signals constitute a potential smoking gun signature for annihilating or decaying dark matter particles that could relatively easily be distinguished from astrophysical or instrumental backgrounds. We provide an updated assessment of the sensitivity of the Cherenkov Telescope Array (CTA) to such signals, based on observations of the Galactic centre region as well as of selected dwarf spheroidal galaxies. We find that current limits and detection prospects for dark matter masses above 300 GeV will be significantly improved, by up to an order of magnitude in the multi-TeV range. This demonstrates that CTA will set a new standard for gamma-ray astronomy also in this respect, as the world's largest and most sensitive high-energy gamma-ray observatory, in particular due to its exquisite energy resolution at TeV energies and the adopted observational strategy focussing on regions with large dark matter densities. Throughout our analysis, we use up-to-date instrument response functions, and we thoroughly model the effect of instrumental systematic uncertainties in our statistical treatment. We further present results for other potential signatures with sharp spectral features, e.g. box-shaped spectra, that would likewise very clearly point to a particle dark matter origin

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin

Single immune checkpoint blockade has shown limited activity in patients with neuroendocrine neoplasms (NENs). Here the authors report the results of a phase II clinical trial of durvalumab (anti-PD-L1) and tremelimumab (anti CTLA-4) in patients with advanced NENs of gastroenteropancreatic and lung origin. Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS

AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients

[Abstract] Introduction. One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection (AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in HT patients can yield diagnostic and prognostic information about AMR. Methods. Genetic variants in 61 genes related to B-cell biology were analyzed by next generation sequencing in 46 HT patients, 23 with and 23 without AMR. Results. We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G, and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4 present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype in control patients. Conclusion. We can conclude that polymorphisms in genes related to the biology of B-cells could have an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene could potentially increase the risk of AMR.Instituto de Salud Carlos III; PI13/0217

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years

Genetic and Chemical Modifiers of a CUG Toxicity Model in Drosophila

Non-coding CUG repeat expansions interfere with the activity of human Muscleblind-like (MBNL) proteins contributing to myotonic dystrophy 1 (DM1). To understand this toxic RNA gain-of-function mechanism we developed a Drosophila model expressing 60 pure and 480 interrupted CUG repeats in the context of a non-translatable RNA. These flies reproduced aspects of the DM1 pathology, most notably nuclear accumulation of CUG transcripts, muscle degeneration, splicing misregulation, and diminished Muscleblind function in vivo. Reduced Muscleblind activity was evident from the sensitivity of CUG-induced phenotypes to a decrease in muscleblind genetic dosage and rescue by MBNL1 expression, and further supported by the co-localization of Muscleblind and CUG repeat RNA in ribonuclear foci. Targeted expression of CUG repeats to the developing eye and brain mushroom bodies was toxic leading to rough eyes and semilethality, respectively. These phenotypes were utilized to identify genetic and chemical modifiers of the CUG-induced toxicity. 15 genetic modifiers of the rough eye phenotype were isolated. These genes identify putative cellular processes unknown to be altered by CUG repeat RNA, and they include mRNA export factor Aly, apoptosis inhibitor Thread, chromatin remodelling factor Nurf-38, and extracellular matrix structural component Viking. Ten chemical compounds suppressed the semilethal phenotype. These compounds significantly improved viability of CUG expressing flies and included non-steroidal anti-inflammatory agents (ketoprofen), muscarinic, cholinergic and histamine receptor inhibitors (orphenadrine), and drugs that can affect sodium and calcium metabolism such as clenbuterol and spironolactone. These findings provide new insights into the DM1 phenotype, and suggest novel candidates for DM1 treatments

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004