Expression of V1A and GRP receptors leads to cellular transformation and increased sensitivity to substance-P analogue-induced growth inhibition.

Small-cell lung cancer (SCLC) is a particularly aggressive cancer, which metastasises early. Despite initial sensitivity to radio- and chemo-therapy, it invariably relapses, so that the 2-year survival remains less than 5%. Neuropeptides particularly arginine vasopressin (AVP) and gastrin-releasing peptide (GRP) act as autocrine and paracrine growth factors and the expression of these and their receptors are a hallmark of the disease. Substance-P analogues including [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-substance-P (SP-D) and [Arg6,D-Trp7,9,NmePhe8]-substance-P (6-11) (SP-G) inhibit the growth of SCLC cells by modulating neuropeptide signalling. We show that GRP and V1A receptors expression leads to the development of a transformed phenotype. Addition of neuropeptide provides some protection from etoposide-induced cytotoxicity. Receptor expression also leads to an increased sensitivity to substance-P analogue-induced growth inhibition. We show that SP-D and SP-G act as biased agonists at GRP and V1A receptors causing blockade of Gq-mediated Ca2+ release while directing signalling to activate ERK via a pertussis toxin-sensitive pathway. This is the first description of biased agonism at V1A receptors. This unique pharmacology governs the antiproliferative properties of these agents and highlights their potential therapeutic potential for the treatment of SCLC and particularly in tumours, which have developed resistance to chemotherapy

Functional annotation of the transcriptome of Sorghum bicolor in response to osmotic stress and abscisic acid

<p>Abstract</p> <p>Background</p> <p>Higher plants exhibit remarkable phenotypic plasticity allowing them to adapt to an extensive range of environmental conditions. Sorghum is a cereal crop that exhibits exceptional tolerance to adverse conditions, in particular, water-limiting environments. This study utilized next generation sequencing (NGS) technology to examine the transcriptome of sorghum plants challenged with osmotic stress and exogenous abscisic acid (ABA) in order to elucidate genes and gene networks that contribute to sorghum's tolerance to water-limiting environments with a long-term aim of developing strategies to improve plant productivity under drought.</p> <p>Results</p> <p>RNA-Seq results revealed transcriptional activity of 28,335 unique genes from sorghum root and shoot tissues subjected to polyethylene glycol (PEG)-induced osmotic stress or exogenous ABA. Differential gene expression analyses in response to osmotic stress and ABA revealed a strong interplay among various metabolic pathways including abscisic acid and 13-lipoxygenase, salicylic acid, jasmonic acid, and plant defense pathways. Transcription factor analysis indicated that groups of genes may be co-regulated by similar regulatory sequences to which the expressed transcription factors bind. We successfully exploited the data presented here in conjunction with published transcriptome analyses for rice, maize, and Arabidopsis to discover more than 50 differentially expressed, drought-responsive gene orthologs for which no function had been previously ascribed.</p> <p>Conclusions</p> <p>The present study provides an initial assemblage of sorghum genes and gene networks regulated by osmotic stress and hormonal treatment. We are providing an RNA-Seq data set and an initial collection of transcription factors, which offer a preliminary look into the cascade of global gene expression patterns that arise in a drought tolerant crop subjected to abiotic stress. These resources will allow scientists to query gene expression and functional annotation in response to drought.</p

Body mass index and self-perception of overweight and obesity in rural, urban and rural-to-urban migrants: PERU MIGRANT study.

OBJECTIVE: This study aimed to compare self-reported weight and body mass index (BMI) in order to determine discrepancies between subjective and objective obesity-related markers, and possible explanatory factors of overweight and obesity underestimation, in urban, rural and migrant populations. MATERIALS AND METHODS: Data from the PERU MIGRANT study, a cross-sectional study, in low-income settings, of urban, migrant (rural-to-urban), and rural groups, including BMI, self-reported weight and socio-demographic indicators were analyzed. Percentage of concurrences between BMI and self-reported weight and Kappa coefficients for inter-rater agreement were calculated. Univariate and standardized descriptive analyses were performed to identify potential explanatory variables for weight underestimation in only overweight and obese individuals, using established BMI and waist circumference cut offs. RESULTS: 983 Participants-199 urban, 583 migrants and 201 rural-were analyzed. Based on BMI, overall prevalence of obesity was 20.1% (95% CI 17.6%-22.6%), and overweight was 38.3% (95% CI 35.2%-41.2%), with differences between study groups (p<0.001). Only 43% of the whole sample had matching self-reported weight and BMI status, whereas 54% underestimated and 3% overestimated their BMI category. Kappa coefficient, between BMI and self-reported weight, for the entire sample was 0.16, rural residents had the lowest coefficient (0.01) and the most underestimation, especially in the overweight category. In overweight and obese individuals, deprivation index (p = 0.016), age (p = 0.014) and waist circumference (p<0.001) were associated with weight underestimation. DISCUSSION: Overall, high levels of overweight, obesity, and underestimation of BMI status were found, with poor agreement between BMI and self-reported weight, showing the unawareness of weight status severity in this low-income setting

Extratores aquosos para a caracterização química de substratos para plantas Water extracts for the chemical characterization of plant substrates

Substratos são materiais que apresentam as mais variadas origens e composições, podendo ser orgânicos, minerais ou sintéticos. Avaliou-se métodos aquosos usando as proporções de 1:1,5; 1:2; 1:2'; 1:5; 1:5' e 1:10 para a determinação de pH, CE, macro e micronutrientes em diferentes substratos comerciais e em componentes de substratos tendo-se como referência os resultados obtidos com o extrato de saturação. Foram utilizados nove substratos recomendados para as culturas de fumo, café, flores (2), florestais, citros e hortaliças (3) e onze componentes: casca de arroz carbonizada, turfa, turfa fibrosa, vermiculita, perlita, casca de pinus compostada (2), argila expandida, fibra de coco, cortiça e pó de xaxim. Foram determinados o pH, condutividade elétrica (EC), macronutrientes e micronutrientes. Os resultados obtidos com pH e EC apresentaram os menores valores de coeficiente de variação (CV) e para os micronutrientes foram muito próximos aos limites de detecção do aparelho. Os macronutrientes apresentaram coeficientes de variação entre 5,1% e 47,2%. O método 1:2 apresentou capacidade extrativa de macro e micronutrientes mais próxima daquela observada para o extrato de saturação e todas as soluções aquosas foram eficientes em avaliar o pH, CE e macronutrientes dos diversos componentes e substratos.<br>Substrates used to grow plants have different origins and compositions and can be organic, mineral or synthetic materials. In the present work the effect of different water extracts (1:1.5; 1:2; 1:2'; 1:5; 1:5'; and 1:10) was evaluated and compared to saturated extracts for the determination of pH, electric conductivity, macro and micronutrients in commercially available products and some of their components. The results were compared to those with saturated extracts. Nine substrates were evaluated, recommended for the cultivation of tobacco, coffee, flowers (2), forestry species, citrus and horticulture species (3), and eleven substrate components: carbonized rice hulls, peat, fiber peat, vermiculite, perlite, Pinus bark compost (2), expanded clay, coir (coconut fiber), cork and 'xaxim' or 'samambaia-açu' (Dicksonia sellowiana). Chemical analyses were made in the substrate extract solutions for the determination of pH, electrical conductivity (EC), and macronutrient and micronutrient concentrations. The pH and EC data showed the lowest coefficients of variation. The micronutrient concentrations in the water extracts were very close to the equipment detection limits. The macronutrient concentrations showed coefficients of variation ranging from 5.1% to 47.2%. The method using the ratio 1:2 was better to obtain the saturation extracts for either macro or micronutrients. In spite of that, for all the other water extracts studied good results were obtained in the evaluation of pH, CE and macronutrientes in the tested samples