Função de genes associados à precipitação envolvidos na adaptação local da abelha ibérica

O aparecimento de novas tecnologias em estudos genómicos permite-nos realizar análises mais aprofundadas e compreender de que modo as forças evolutivas atuam sobre o genoma dos organismos. Um scan genómico realizado previamente na abelha ibérica, revelou genes associados a imunidade, detoxificação e mecanismo da visão, estando alguns deles associados a variáveis ambientais (Chávez-Galarza et al. 2013). Na sequência deste estudo procurou se sinais de seleção em genomas completos de 84 indivíduos de abelha ibérica, integrando informação genética, geográfica e ambiental. Detetou-se a presença 315 genes associados à precipitação. O principal objetivo é caracterizar a função destes genes, e também tentar perceber que tipos de substituições nucleotídicas ocorrem nas sequências codificantes das proteínas. Para isso utilizaram se diversas bases genómicas, como o NCBI, BeeBase e Flybase, as quais mostraram que 51 das variações, presentes em 28 genes, são não-sinónimas, originando aminoácidos diferentes.info:eu-repo/semantics/publishedVersio

Cartografia do retardo estatural em escolares do Estado da Paraíba, Brasil

OBJECTIVE: The study is part of a project financed by the United Nations (FAO) and the Ministry of Education of Brazil (Fundação de Assistência ao Escolar) which intends to evaluate the nutritional status of public schools students in order to estimate, giving emphasis to geographical aspects, the magnitude and distribution of statural deficit of this population in the Paraíba State, Northeastern Brazil. METHODS: Schoolchildren, aged 6-9 years and enrolled in the first grade inall municipalities of Paraíba state went through a height survey. We consider as statural deficit values below -2 standard deviations according to the anthropometric pattern of National Center of Health Statistics. RESULTS: A frequency of 14.5% of statural deficit was found in the whole state , as well as 18.7% in the semidesertic region (sertão), 13.8% in Agreste area, 11.9% in Borborema region and 10.9% in Mata zone. In rural area, the prevalence of statural deficit was higher (17.8%) than for those living in urban area (11.8%). CONCLUSIONS: The results reveal a process of inlanding of statural deficit, which contrasts with historical descriptions of the geographical distribution of this problem in the Northeastern region of Brazil.OBJETIVO: Parte de um projeto promovido pelas Nações Unidas (FAO) e pelo Ministério da Educação do Brasil (Fundação de Assistência ao Escolar) para estudar a condição nutricional de alunos de educandários públicos, visa a avaliar, com um enfoque cartográfico, a magnitude e a distribuição espacial do déficit estatural de alunos de escolas públicas do Estado da Paraíba. MÉTODOS: Fez-se levantamento de caráter censitário da estatura de 50.144 escolares com idade de 6 a 9 anos, matriculados na primeira série do primeiro grau de todos municípios do Estado da Paraíba, considerando-se como déficit estatural os valores classificados abaixo de -2 "scores" z do padrão do National Center of Health Statistics. RESULTADOS: Em todo o Estado, 14,5% dos escolares foram considerados casos de nanismo, com uma distribuição heterogênea para as quatro mesorregiões fisiográficas estudadas: 18,7% no Sertão, 13,8% no Agreste, 11,9% na Borborema e 10,9% na Zona da Mata. Nas escolas da área rural, 17,8% dos alunos apresentavam déficit estatural, enquanto no meio urbano a prevalência de nanismo foi de 11,8%. CONCLUSÕES: Os dados encontrados são indicativos de um processo de interiorização da desnutrição, contrastando substancialmente com as descrições históricas sobre a cartografia do problema na região

A strategy for the identification of new abiotic stress determinants in arabidopsis using web-based data mining and reverse genetics

Since the sequencing of the Arabidopsis thaliana genome in 2000, plant researchers have faced the complex challenge of assigning function to thousands of genes. Functional discovery by in silico prediction or homology search resolved a significant number of genes, but only a minor part has been experimentally validated. Arabidopsis entry into the post-genomic era signified a massive increase in high-throughput approaches to functional discovery, which have since become available through publicly-available web-based resources. The present work focuses on an easy and straightforward strategy that couples data-mining to reverse genetics principles, to allow for the identification of new abiotic stress determinant genes. The strategy explores systematic microarray-based transcriptomics experiments, involving Arabidopsis abiotic stress responses. An overview of the most significant resources and databases for functional discovery in Arabidopsis is presented. The successful application of the outlined strategy is illustrated by the identification of a new abiotic stress determinant gene, HRR, which displays a heat stress-related phenotype after a loss-of-function reverse genetics approach.No competing financial interests exist. The present work was supported by Foundation for Science and Technology (POCTI/AGR/45462/2002). H. Azevedo (SFRH/BPD/17198/2004), J. Correia (SFRH/BD/16663/2004), J. Oliveira (SFRH/BD/38379/2007), S. Laranjeira (SFRH/BD/29778/2006), C. Barbeta (SFRH/BD/12081/2003) and V. Amorim-Silva (SFRH/BD/29778/2006) were supported by Foundation for Science and Technology

Cell adhesion and Ca2+ signaling activity in stably transfected trypanosoma cruzi epimastigotes expressing the metacyclic stage-specific surface molecule gp82

Metacyclic trypomastigotes of Trypanosoma cruzi express a developmentally regulated 82-kDa surface glycoprotein (gp82) that has been implicated in host cell invasion. gp82-mediated interaction of metacyclic forms with target cells induces in both cells activation of the signal transduction pathways, leading to intracellular Ca2+ mobilization, which is required for parasite internalization. Noninfective epimastigotes do not express detectable levels of gp82 and are unable to induce a Ca2+ response. We stably transfected epimastigotes with a T. cruzi expression vector carrying the metacyclic stage gp82 cDNA. These transfectants produced a functional gp82, which bound to and triggered a Ca2+ response in HeLa cells, in the same manner as the metacyclic trypomastigote gp82. Such properties were not found in epimastigotes transfected with the plasmid vector alone. Epimastigotes expressing gp82 on the surface adhered to HeLa cells but were not internalized. Treatment of gp82-expressing epimastigotes with forskolin, an activator of adenylyl cyclase that increases the metacyclic trypomastigote entry into target cells, did not promote parasite internalization. P175, an intracellular tyrosine phosphorylated protein, which appears to play a role in gp82-dependent signaling cascade in metacyclic forms, was undetectable in epimastigotes, either transfected or not with pTEX-gp82. Overall, our results indicate that gp82 is required but not sufficient for target cell invasion.Universidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, BR-04023062 São Paulo, BrazilWeb of Scienc

The prevalence and importance of frailty in heart failure with reduced ejection fraction – an analysis of PARADIGM-HF and ATMOSPHERE

Aims: Frailty, characterized by loss of homeostatic reserves and increased vulnerability to physiological decompensation, results from an aggregation of insults across multiple organ systems. Frailty can be quantified by counting the number of ‘health deficits’ across a range of domains. We assessed the frequency of, and outcomes related to, frailty in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results: Using a cumulative deficits approach, we constructed a 42‐item frailty index (FI) and applied it to identify frail patients enrolled in two HFrEF trials (PARADIGM‐HF and ATMOSPHERE). In keeping with previous studies, patients with FI ≤0.210 were classified as non‐frail and those with higher scores were divided into two categories using score increments of 0.100. Clinical outcomes were examined, adjusting for prognostic variables. Among 13 625 participants, mean (± standard deviation) FI was 0.250 (0.10) and 8383 patients (63%) were frail (FI >0.210). The frailest patients were older and had more symptoms and signs of heart failure. Women were frailer than men. All outcomes were worse in the frailest, with high rates of all‐cause death or all‐cause hospitalization: 40.7 (39.1–42.4) vs. 22.1 (21.2–23.0) per 100 person‐years in the non‐frail; adjusted hazard ratio 1.63 (1.53–1.75) (P < 0.001). The rate of all‐cause hospitalizations, taking account of recurrences, was 61.5 (59.8–63.1) vs. 31.2 (30.3–32.2) per 100 person‐years (incidence rate ratio 1.76; 1.62–1.90; P < 0.001). Conclusion: Frailty is highly prevalent in HFrEF and associated with greater deterioration in quality of life and higher risk of hospitalization and death. Strategies to prevent and treat frailty are needed in HFrEF

Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents

Leishmaniasis is a group of parasitic diseases with the potential to infect more than 1 billion people; however, its treatment is still old and inadequate. In order to contribute to changing this view, this work consisted of the development of complexes derived from MI metal ions with thioureas, aiming to obtain potential leishmanicidal agents. The thiourea ligands (HLR) were obtained by reactions of p-toluenesulfohydrazide with R-isothiocyanates and were used in complexation reactions with AgI and AuI, leading to the formation of complexes of composition [M(HLR)2]X (M = Ag or Au; X = NO3− or Cl−). All compounds were characterized by FTIR, 1H NMR, UV-vis, emission spectroscopy and elemental analysis. Some representatives were additionally studied by ESI-MS and single-crystal XRD. Their properties were further analyzed by DFT calculations. Their cytotoxicity on Vero cells and the extracellular leishmanicidal activity on Leishmania infantum and Leishmania braziliensis cells were evaluated. Additionally, the interaction of the complexes with the Old Yellow enzyme of the L. braziliensis (LbOYE) was examined. The biological tests showed that some compounds present remarkable leishmanicidal activity, even higher than that of the standard drug Glucantime, with different selectivity for the two species of Leishmania. Finally, the interaction studies with LbOYE revealed that this enzyme could be one of their biological targets

Development of Inhalable Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in microparticulate system for antituberculosis drug delivery

Tuberculosis (TB) is an infectious disease which affects millions of people worldwide. Inhalable polymeric dry powders are promising alternatives as anti-TB drug carriers to the alveoli milieu and infected macrophages, with potential to significantly improve the therapeutics efficiency. Here, the development of a magnetically responsive microparticulate system for pulmonary delivery of an anti-TB drug candidate (P3) is reported. Microparticles (MPs) are developed based on a cast method using calcium carbonate sacrificial templates and incorporate superparamagnetic iron oxide nanoparticles to concentrate MPs in alveoli and enable drug on demand release upon actuation of an external alternate magnetic field (AMF). The MPs are shown to be suitable for P3 delivery to the lower airways and for alveolar macrophage phagocytosis. The developed MPs reveal unique and promising features to be used as an inhalable dry powder allowing the AMF control over dosage and frequency of drug delivery anticipating improved TB treatments.The authors wish to acknowledge the financial support from the Portuguese Foundation for Science and Technology (FCT) for the postdoctoral grant of M.S.M. (SFRH/BPD/110868/2015) and R.M.A.D (SFRH/BPD/112459/2015), FCT grant of E.T. (IF/01390/2014) and Recognize project (UTAP-ICDT/CTM-BIO/0023/2014). This article is also a result of the project “Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechnologies, marine-derived biomaterials and stem cells,” supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The authors acknowledge the financial support from the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant Agreement No. 739572 – The Discoveries CTR.info:eu-repo/semantics/publishedVersio

Quality of life in men and women with heart failure:association with outcome, and comparison between the Kansas City Cardiomyopathy questionnaire and the EuroQol 5 dimensions questionnaire

Aims We sought to analyse quality of life (QoL) measures derived from two questionnaires widely used in clinical trials, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQoL 5 dimensions (EQ-5D), and to compare their prognostic value in men and women with heart failure and reduced ejection fraction (HFrEF). Methods and results From the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) we compared KCCQ and EQ-5D at baseline and after 9 months in 1276 men and 373 women with new-onset or worsening symptoms of HFrEF, who were sub-optimally treated and in whom there was an anticipated up-titration of guideline-derived medical therapies. Women had significantly worse baseline QoL (median) as compared with men, both when assessed with KCCQ overall score (KCCQ-OS, 44 vs. 53, P 0.2). Conclusion Amongst patients with HFrEF, women reported significantly worse QoL than men. QoL was independently associated with subsequent outcome, similarly in men and women. The KCCQ in general, and the KCCQ-OS in particular, showed the strongest independent association with outcome.publishedVersio