Giant FAZ10 is required for flagellum attachment zone stabilization and furrow positioning in Trypanosoma brucei

The flagellum and flagellum attachment zone (FAZ) are important cytoskeletal structures in trypanosomatids, being required for motility, cell division and cell morphogenesis. Trypanosomatid cytoskeletons contain abundant high molecular mass proteins (HMMPs), but many of their biological functions are still unclear. Here, we report the characterization of the giant FAZ protein, FAZ10, in Trypanosoma brucei, which, using immunoelectron microscopy, we show localizes to the intermembrane staples in the FAZ intracellular domain. Our data show that FAZ10 is a giant cytoskeletal protein essential for normal growth and morphology in both procyclic and bloodstream parasite life cycle stages, with its depletion leading to defects in cell morphogenesis, flagellum attachment, and kinetoplast and nucleus positioning. We show that the flagellum attachment defects are probably brought about by reduced tethering of the proximal domain of the paraflagellar rod to the FAZ filament. Further, FAZ10 depletion also reduces abundance of FAZ flagellum domain protein, ClpGM6. Moreover, ablation of FAZ10 impaired the timing and placement of the cleavage furrow during cytokinesis, resulting in premature or asymmetrical cell division

Oxidative status imbalance in patients with metabolic syndrome: Role of the myeloperoxidase/hydrogen peroxide axis

The present study evaluated the cardiometabolic and redox balance profiles in patients with Metabolic Syndrome compared to apparently healthy individuals, and the participation of the myeloperoxidase/hydrogen peroxide axis in systemic lipid peroxidation. Twenty-four patients with Metabolic Syndrome and eighteen controls underwent a full clinical assessment. Venous blood samples were collected for general biochemical dosages, as well as for the oxidative stress analyses (superoxide dismutase, catalase, and arginase activities; and lipid peroxidation, myeloperoxidase activity, nitrite, and hydrogen peroxide concentrations in plasma). Arterial stiffness was assessed by radial artery applanation tonometry. Plasma lipid peroxidation, erythrocyte superoxide dismutase activity, myeloperoxidase activity, and hydrogen peroxide concentrations were shown to be increased in Metabolic Syndrome patients, without significant differences for the other enzymes, plasma nitrite concentrations, and arterial stiffness. Linear regression analysis revealed a positive and significant correlation between lipid peroxidation and myeloperoxidase and also between this enzyme and hydrogen peroxide. In contrast, such correlation was not observed between lipid peroxidation and hydrogen peroxide. In summary, Metabolic Syndrome patients exhibited evident systemic redox imbalance compared to controls, with the possible participation of the myeloperoxidase/hydrogen peroxide axis as a contributor in lipid peroxidation

O Sistema Endocanabinóide – uma perspetiva terapêutica

Although the medicinal use of Cannabis sativa derivatives is well known since antiquity, the study of their properties expanded recently with the discovery of an endogenous cannabinoid system, which comprises the endogenous cannabis-like ligands (endocannabinoids), the cannabinoid receptors (CB1 and CB2) and the enzymes involved in their metabolism. Since the discovery of the endocannabinoid system (ECS), the scientific community focused on research of its clinical use and achieved important findings during the last decade. In some countries, cannabis derivatives are a pharmacological option for appetite stimulation and pain treatment. However, the first ECS-based drug rimonabant (a CB1 antagonist), approved for the treatment obesity with associated risk factors, was withdrawn due to safety concerns. Nowadays, based on the growing evidences resulting from preclinical and clinical studies of ECS modulators, these drugs are currently pointed out as novel therapeutic approaches for several pathophysiological conditions. Here, we review the potential role of (endo)cannabinoid system in therapeutics and the recent designed strategies for the development of drugs that target this system. A utilização terapêutica da Cannabis sativa ou seus derivados é conhecida há muitos anos, no entanto, o estudo das suas propriedades despontou recentemente com a descoberta de um sistema canabinóide endógeno (ECS). O ECS compreende os compostos endógenos similares ao tetrahidrocanabinol (endocanabinóides), os recetores canabinóides (CB1 e CB2) e as enzimas envolvidas no seu metabolismo. Desde a descoberta do ECS, a comunidade científica focou-se na investigação do seu potencial clínico com resultados encorajadores. Em alguns países, os derivados da cannabis constituem uma opção farmacológica na estimulação do apetite e tratamento da dor. O primeiro medicamento baseado no ECS, o rimonabant (um antagonista CB1), foi aprovado para o tratamento da obesidade associada a outros fatores de risco, no entanto foi retirado por questões de segurança. Atualmente, e baseadas nos estudos pré-clínicos e clínicos, existem várias evidências do seu interesse clínico na modulação de diversas condições fisiopatológicas. Neste artigo discutimos o papel potencial do sistema (endo)canabinóide na terapêutica e as recentes estratégias desenvolvidas na modulação do sistema.

Compilation of parameterized seismogenic sources in Iberia for the SHARE European-scale seismic source model.

Abstract: SHARE (Seismic Hazard Harmonization in Europe) is an EC-funded project (FP7) that aims to evaluate European seismic hazards using an integrated, standardized approach. In the context of SHARE, we are compiling a fully-parameterized active fault database for Iberia and the nearby offshore region. The principal goal of this initiative is for fault sources in the Iberian region to be represented in SHARE and incorporated into the source model that will be used to produce seismic hazard maps at the European scale. The SHARE project relies heavily on input from many regional experts throughout the Euro-Mediterranean region. At the SHARE regional meeting for Iberia, the 2010 Working Group on Iberian Seismogenic Sources (WGISS) was established; these researchers are contributing to this large effort by providing their data to the Iberian regional integrators in a standardized format. The development of the SHARE Iberian active fault database is occurring in parallel with IBERFAULT, another ongoing effort to compile a database of active faults in the Iberian region. The SHARE Iberian active fault database synthesizes a wide range of geological and geophysical observations on active seismogenic sources, and incorporates existing compilations (e.g., Cabral, 1995; Silva et al., 2008), original data contributed directly from researchers, data compiled from the literature, parameters estimated using empirical and analytical relationships, and, where necessary, parameters derived using expert judgment. The Iberian seismogenic source model derived for SHARE will be the first regional-scale source model for Iberia that includes fault data and follows an internationally standardized approach (Basili et al., 2008; 2009). This model can be used in both seismic hazard and risk analyses and will be appropriate for use in Iberian- and European-scale assessments

Genome sequence and effectorome of Moniliophthora perniciosa and Moniliophthora roreri subpopulations

Background: The hemibiotrophic pathogens Moniliophthora perniciosa (witches' broom disease) and Moniliophthora roreri (frosty pod rot disease) are among the most important pathogens of cacao. Moniliophthora perniciosa has a broad host range and infects a variety of meristematic tissues in cacao plants, whereas M. roreri infects only pods of Theobroma and Herrania genera. Comparative pathogenomics of these fungi is essential to understand Moniliophthora infection strategies, therefore the detection and in silico functional characterization of effector candidates are important steps to gain insight on their pathogenicity. Results: Candidate secreted effector proteins repertoire were predicted using the genomes of five representative isolates of M. perniciosa subpopulations (three from cacao and two from solanaceous hosts), and one representative isolate of M. roreri from Peru. Many putative effectors candidates were identified in M. perniciosa: 157 and 134 in cacao isolates from Bahia, Brazil; 109 in cacao isolate from Ecuador, 92 and 80 in wild solanaceous isolates from Minas Gerais (Lobeira) and Bahia (Caiçara), Brazil; respectively. Moniliophthora roreri showed the highest number of effector candidates, a total of 243. A set of eight core effectors were shared among all Moniliophthora isolates, while others were shared either between the wild solanaceous isolates or among cacao isolates. Mostly, candidate effectors of M. perniciosa were shared among the isolates, whereas in M. roreri nearly 50% were exclusive to the specie. In addition, a large number of cell wall-degrading enzymes characteristic of hemibiotrophic fungi were found. From these, we highlighted the proteins involved in cell wall modification, an enzymatic arsenal that allows the plant pathogens to inhabit environments with oxidative stress, which promotes degradation of plant compounds and facilitates infection. Conclusions: The present work reports six genomes and provides a database of the putative effectorome of Moniliophthora, a first step towards the understanding of the functional basis of fungal pathogenicity. © 2018 The Author(s).This work was done in the frame of the International Consortium in Advanced Biology (CIBA; https://www.ciba-network.org). The authors thank the Molecular Plant Pathology Laboratory and the Plant Pathology Laboratory at INIAP personnel for their assistance in obtaining the DNAs, Dr Carmen Suarez Capello for her kind assistance in Ecuador, and the Núcleo de Biologia Computacional e Gestão de Informações Biotecnológicas - UESC (NBCGIB), and Copenhague University for providing bioinformatics facility. Data sets were processed in sagarana HPC cluster, CPAD-ICB-UFMG. The authors would also like to thank Dr. Claudia Fortes Ferreira (Embrapa CNPMF, Brazil) and Dr. Raul Renné Valle (CEPLAC/CEPEC, Brazil) for English language revision. We are also grateful to Ivanna Michelle Meraz Pérez for helping translating an early version of this manuscript and to the anonymous reviewers who provided helpful comments to our work. KPG, FM and CPP were supported by research fellowship Pq-1 from CNPq. National Council for Scientific Development (CNPq) n° 311759/2014–9. CSB acknowledges FAPESB (Foundation for Research Support of the State of Bahia) for supporting her with a research assistantship during her Master’s Programme

Valor nutritivo de pastagens de capim-elefante manejadas sob sistema convencional e agroecológico.

O capim-elefante é utilizado, na sua grande maioria, em sistemas convencionais de produção animal. O objetivo deste trabalho foi comparar o valor nutritivo do capimelefante em sistemas de manejo agroecológico e convencional, quanto a proteína bruta (PB), fibra em detergente neutro (FDN) e digestibilidade in vitro da matéria seca (DIVMS). Foram usados quatro piquetes, com 0,12ha cada um. No sistema convencional, o capim-elefante foi estabelecido singularmente. No sistema agroecológico, o plantio foi feito em linhas afastadas de 3m. Nas entrelinhas, estabeleceu-se a aveia e o azevém no período hibernal, enquanto que no período estival permitiu-se o desenvolvimento de espécies espontâneas. A adubação foi feita com fertilizantes orgânicos (150kg ha-1 de N). No sistema agroecológico, foram conduzidos sete pastejos, de 24/04/2004 a 05/05/2005. Na pastagem convencional, usouse a mesma quantidade de N (uréia), sendo conduzidos quatro ciclos de pastejo, de 06/10/2004 a 05/05/2005. Para ambos os sistemas foram utilizadas vacas da raça Holandês, recebendo complementação alimentar de 3,5kg dia-1 de concentrado com 20% de proteína bruta, constituindo-se nos animais experimentais. Nas avaliações, considerou-se a massa de forragem inicial com base na matéria seca (MS), os componentes botânicos da pastagem e estruturais do capimelefante. As análises de qualidade foram feitas em amostras de pastejo simulado. O delineamento experimental foi o inteiramente casualizado com dois tratamentos, convencional e agroecológico, duas repetições (piquetes) e em parcelas incompletas subdivididas no tempo (pastejos). Houve interação (P<0,05) entre tratamentos e pastejos em todas as variáveis. Na pastagem agroecológica, o modelo que melhor se ajustou foi o cúbico para todas as variáveis, em função do tempo de pastejo. Na pastagem convencional, a PB e a DIVMS ajustaram-se melhor ao modelo linear, com taxa positiva de crescimento, sendo observado comportamento inverso para FDN, com o decorrer dos pastejos. Tanto na pastagem convencional quanto na agroecológica encontraram-se associações negativas entre lâmina foliar do capim-elefante com PB e DIVMS e positiva com FDN. Ambos os sistemas apresentaram teores qualitativos elevados das pastagens, considerando-se a adubação, o manejo e o tempo de utilização