Purification and functional characterisation of rhiminopeptidase A, a novel aminopeptidase from the venom of Bitis gabonica rhinoceros

This study describes the discovery and characterisation of a novel aminopeptidase A from the venom of B. g. rhinoceros and highlights its potential biological importance. Similar to mammalian aminopeptidases, rhiminopeptidase A might be capable of playing roles in altering the blood pressure and brain function of victims. Furthermore, it could have additional effects on the biological functions of other host proteins by cleaving their N-terminal amino acids. This study points towards the importance of complete analysis of individual components of snake venom in order to develop effective therapies for snake bites

Scanning and filling : ultra-dense SNP genotyping combining genotyping-by-sequencing, SNP array and whole-genome resequencing data

Genotyping-by-sequencing (GBS) represents a highly cost-effective high-throughput genotyping approach. By nature, however, GBS is subject to generating sizeable amounts of missing data and these will need to be imputed for many downstream analyses. The extent to which such missing data can be tolerated in calling SNPs has not been explored widely. In this work, we first explore the use of imputation to fill in missing genotypes in GBS datasets. Importantly, we use whole genome resequencing data to assess the accuracy of the imputed data. Using a panel of 301 soybean accessions, we show that over 62,000 SNPs could be called when tolerating up to 80% missing data, a five-fold increase over the number called when tolerating up to 20% missing data. At all levels of missing data examined (between 20% and 80%), the resulting SNP datasets were of uniformly high accuracy (96– 98%). We then used imputation to combine complementary SNP datasets derived from GBS and a SNP array (SoySNP50K). We thus produced an enhanced dataset of >100,000 SNPs and the genotypes at the previously untyped loci were again imputed with a high level of accuracy (95%). Of the >4,000,000 SNPs identified through resequencing 23 accessions (among the 301 used in the GBS analysis), 1.4 million tag SNPs were used as a reference to impute this large set of SNPs on the entire panel of 301 accessions. These previously untyped loci could be imputed with around 90% accuracy. Finally, we used the 100K SNP dataset (GBS + SoySNP50K) to perform a GWAS on seed oil content within this collection of soybean accessions. Both the number of significant marker-trait associations and the peak significance levels were improved considerably using this enhanced catalog of SNPs relative to a smaller catalog resulting from GBS alone at 20% missing data. Our results demonstrate that imputation can be used to fill in both missing genotypes and untyped loci with very high accuracy and that this leads to more powerful genetic analyses

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Adiponectin inhibits neutrophil phagocytosis of Escherichia coli by inhibition of PKB and ERK 1/2 MAPK signalling and Mac-1 activation

Full length adiponectin is a potent immune modulatory adipokine, impacting upon the actions of several immune cells. Neutrophil oxidative burst has been shown to decrease in response to adiponectin, and we speculated that it could have other effects on neutrophil function. Here we report that adiponectin reduces the phagocytic ability of human neutrophils, decreasing significantly the ingestion of opsonised E. coli by these cells in whole blood (p<0.05) and as isolated neutrophils (p<0.05). We then determined the mechanisms involved. We observed that the activation of Mac-1, the receptor engaged in complement-mediated phagocytosis, was decreased by adiponectin in response to E. coli stimulation. Moreover, treatment of neutrophils with adiponectin prior to incubation with E. coli significantly inhibited signalling through the PI3K/PKB and ERK 1/2 pathways, with a parallel reduction of F-actin content. Studies with pharmacological inhibitors showed that inhibition of PI3K/PKB, but not ERK 1/2 signalling was able to prevent the activation of Mac-1. In conclusion, we propose that adiponectin negatively affects neutrophil phagocytosis, reducing the uptake of E. coli and inhibiting Mac-1 activation, the latter by blockade of the PI3K/PKB signal pathway

Searching in Silico Novel Targets for Specific Coffee Rust Disease Control

International audienceCoffee industry is threatened by production losses due to the rust disease since 1850. The coffee leaf rust (CLR) disease has an important social and economical impacts and its control is still a challenge. The CLR pathogen is the fungus Hemileia vastatrix Berkeley & Broome (Basidiomycota, order Pucciniales) that is currently controlled by using non-specific anti-fungal chemicals spraying. The advances in molecular biology and bioinformatics may allow the identification of new targets and environmentally safe strategies for controlling CLR. Several genomic and transcriptomic data are available for H. vastatrix that allow searching for new proteins to achieve a better disease control. We used the dataset of 34,242 sequences from the fungal genome and transcriptome, with a filtering strategy for protein annotation, structure and cell sublocalization to select three essential proteins related to steroid synthesis, cell membrane, and cell wall metabolism. This short paper reports the ongoing study to allow the development of new molecules that might be validated and contribute to new products that are specific and ecologically friendly

Malaria impairs resistance to Salmonella through heme- and heme oxygenase-dependent dysfunctional granulocyte mobilization.

In sub-Saharan Africa, invasive nontyphoid Salmonella (NTS) infection is a common and often fatal complication of Plasmodium falciparum infection. Induction of heme oxygenase-1 (HO-1) mediates tolerance to the cytotoxic effects of heme during malarial hemolysis but might impair resistance to NTS by limiting production of bactericidal reactive oxygen species. We show that co-infection of mice with Plasmodium yoelii 17XNL (Py17XNL) and Salmonella enterica serovar Typhimurium 12023 (Salmonella typhimurium) causes acute, fatal bacteremia with high bacterial load, features reproduced by phenylhydrazine-induced hemolysis or hemin administration. S. typhimurium localized predominantly in granulocytes. Py17XNL, phenylhydrazine and hemin caused premature mobilization of granulocytes from bone marrow with a quantitative defect in the oxidative burst. Inhibition of HO by tin protoporphyrin abrogated the impairment of resistance to S. typhimurium by hemolysis. Thus, a mechanism of tolerance to one infection, malaria, impairs resistance to another, NTS. Furthermore, HO inhibitors may be useful adjunctive therapy for NTS infection in the context of hemolysis

Um estudo dos relatos afetivos subjetivos a estímulos do International Affective Picture System em uma amostra geriátrica brasileira Subjective affective ratings to photographic stimuli of the International Affective Picture System in a Brazilian elderly sample

INTRODUÇÃO: A literatura científica indica a possibilidade de a percepção da emoção e a formação da memória emocional serem discordantes entre jovens e idosos. A mesma é pobre ao explorar essa possibilidade. Neste estudo, relatamos os resultados obtidos em um experimento-piloto com uma amostra de idosos brasileiros, que classificaram subjetivamente, através da escala Self Assessment Manikin, imagens oriundas do International Affective Picture System. MÉTODO: Quarenta e oito idosos voluntários da Universidade Aberta da Terceira Idade, saudáveis clínica e cognitivamente, avaliaram o caráter alertante e a valência afetiva de 71 imagens do International Affective Picture System, aleatoriamente escolhidas. RESULTADOS: O grau de alerta reportado por idosos diante de um estímulo emocional é tanto maior quanto menor o prazer provocado por essa imagem-estímulo, resultando na existência de uma forte correlação negativa (r = 0,93) entre o grau de alerta e o estímulo desprazeroso. Em uma comparação do acima obtido com outro experimento normativo semelhante feito com jovens brasileiros e americanos, apontou-se para uma possível diferença cultural na forma de relatar subjetivamente um estímulo emocional. CONCLUSÕES: Os resultados obtidos com esta amostra estudada sugerem que pode existir uma diferença nos relatos afetivos entre os jovens e idosos, onde uma normatização do International Affective Picture System para uma amostra maior, representativa da população de idosos, seria útil para responder esta questão.<br>INTRODUCTION: The scientific literature points to a possible bias in the form perception and emotional memory are constructed when elderly and young individuals are compared. However, this possibility is underexplored. This paper presents the results obtained from a pilot study based on an elderly emotional subjective report after evaluation using the International Affective Picture System images and Self Assessment Manikin scale scores. METHOD: Forty-eight clinically and cognitively capable elderly volunteer subjects from the Third Age Open University evaluated 71 randomly chosen images of the International Affective Picture System in terms of arousal and affective valence. RESULTS: For the elderly, the greater the arousal, the smaller the pleasure resulting in a strong negative correlation (r = 0.93) observed between arousal and negative valence. A comparison with another similar normative experiment performed in young Brazilian and American individuals showed a possible cultural difference in subjective reports of emotional stimuli. CONCLUSIONS: This investigation indicates that there may be a difference between elderly and young individuals when affective reports of arousal are studied. A normalization of the International Affective Picture System for the elderly in a larger sample, representative of the population, might be useful to address this issue

Antibacterial and cytotoxic activity of Brazilian plant extracts - Clusiaceae

Twelve extracts obtained from nine plants belonging to six different genera of Clusiaceae were analyzed against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Enterococcus faecalis) bacteria using the microdilution broth assay. Tovomita aff. longifolia, T. brasiliensis, Clusia columnaris, Garcinia madruno, Haploclathra paniculata, and Caraipa grandifolia extracts showed significant results against the bacteria. The organic extract obtained from the leaves of T. aff. longifolia showed minimal inhibitory concentration (MIC) = 70 µg/ml and minimal bactericidal concentration (MBC) = 90 µg/ml against E. faecalis and the organic extract made with the stem of C. columnaris showed MIC = 180 µg/ml and MBC = 270 µg/ml against P. aeruginosa. None of the antibacterial extracts showed lethal activity against brine shrimp nauplii. On the other hand, both aqueous and organic extracts obtained from the aerial organs of Vismia guianensis that were cytotoxic to brine shrimp nauplii did not show a significant antibacterial activity in the assay