Levels of organochlorine pesticides are associated with amyloid aggregation in apex avian brains

Organochlorine (OC) pesticides pose a significant environmental risk to wildlife and humans and have been associated with Alzheimer’s disease (AD). This study aims to spectroscopically analyse brains from free-flying birds and link the results to OC exposure and consequent amyloid aggregation. As long-lived apex predators, predatory birds represent a sentinel species similar to humans. Therefore, the results have implications for both species and may also add to our understanding of the role OC pesticides play in the development of AD. Brains of wild sparrowhawks were analysed using ATR-FTIR and Raman spectroscopy and Congo red staining; results were correlated with OC pesticide concentrations in livers. Effects of OC exposure were sex and age dependant and associated alterations were seen in lipids and protein secondary structure. A shift from α-helix to β-sheet conformation of proteins indicated that concentrations of OC pesticides > 7.18 µg/g may lead to cerebral amyloid aggregation

Planting time for maximization of yield of vinegar plant calyx (Hibiscus sabdariffa L.)

Objetivou-se avaliar a produtividade de cálices de Hibiscus sabdariffa L., planta medicinal, em quatro épocas de plantio em Lavras M.G. Os tratamentos foram quatro épocas de plantio (18 de outubro; 15 de novembro; 18 de dezembro de 2001 e 15 de janeiro de 2002) e realizada uma colheita quando praticamente não existiam cálices em desenvolvimento, quase no final do ciclo da planta. Foram considerados os números de cálices por planta, as fitomassas frescas e secas dos cálices e a qualidade. Concluiu-se que a época de plantio influenciou o rendimento por planta e as fitomassas frescas e secas dos cálices, diferindo entre si pelo teste de Tukey a 5%. No plantio de outubro, houve maior rendimento (2.522 kg/ha), com produção de 5,24 vezes a mais em relação ao plantio do mês de janeiro (481 kg/ha). Os plantios nos meses de novembro e dezembro tiveram produções de 1.695 e 1.093 kg.ha-1 de cálices secos, respectivamente, e em relação ao mês de janeiro, a produção foi 3,52 e 2,27 vezes a mais.Deve-se realizar a colheita assim que os cálices estiverem maduros, a fim de preservar a qualidade

Independence in CLP Languages

Studying independence of goals has proven very useful in the context of logic programming. In particular, it has provided a formal basis for powerful automatic parallelization tools, since independence ensures that two goals may be evaluated in parallel while preserving correctness and eciency. We extend the concept of independence to constraint logic programs (CLP) and prove that it also ensures the correctness and eciency of the parallel evaluation of independent goals. Independence for CLP languages is more complex than for logic programming as search space preservation is necessary but no longer sucient for ensuring correctness and eciency. Two additional issues arise. The rst is that the cost of constraint solving may depend upon the order constraints are encountered. The second is the need to handle dynamic scheduling. We clarify these issues by proposing various types of search independence and constraint solver independence, and show how they can be combined to allow dierent optimizations, from parallelism to intelligent backtracking. Sucient conditions for independence which can be evaluated \a priori" at run-time are also proposed. Our study also yields new insights into independence in logic programming languages. In particular, we show that search space preservation is not only a sucient but also a necessary condition for ensuring correctness and eciency of parallel execution

Phenotypic Diversity for Seed Mineral Concentration in North American Dry Bean Germplasm of Middle American Ancestry

Dry bean (Phaseolus vulgaris L.) seeds are a major protein, carbohydrate, and mineral source in the human diet of peoples in multiple regions of the world. Seed mineral biofortification is an ongoing objective to improve this important food source. The objective of this research was to assess the seed mineral concentration of five macroelements and eight microelements in a large panel (n = 277) of modern race Durango and race Mesoamerica genotypes to determine if variability existed that could be exploited for targeted seed biofortification. Varieties that derive from these races are found in many diets throughout the world. The panel was grown in replicated trials under typical production conditions in the major bean growing regions of the United States, and a subset of the panel was also grown in replicated trials at three locations under control and terminal drought conditions. Except for K, seed mineral concentrations were higher for race Mesoamerica genotypes. Significantly higher seed concentrations for the majority of the minerals were observed for white-seeded genotypes and race Durango genotypes with the now preferred indeterminate, upright growth habit. Modern genotypes (since 1997) had equal or increased mineral concentrations compared with older genotypes. Drought affected mineral content differentially, having no effect on the microelement content but increased Co, Fe, and Ni concentrations. The correlation of Ca and Mn concentrations suggests that these elements may share seed deposition mechanisms. The high heritability for seed mineral concentration implies that breeding progress can be achieved by parental selection from this panel

Revealing a novel Otubain-Like Enzyme from Leishmania infantum with deubiquitinating activity toward K48-linked substrate

Deubiquitinating enzymes (DUBs) play an important role in regulating a variety of eukaryotic processes. In this context, exploring the role of deubiquitination in Leishmania infantum could be a promising alternative to search new therapeutic targets for leishmaniasis. Here we present the first characterization of a DUB from L. infantum, otubain (OtuLi), and its localization within parasite. The recombinant OtuLi (rOtuLi) showed improved activity on lysine 48 (K48)-linked over K63-linked tetra-ubiquitin (Ub) and site-directed mutations on amino acids close to the catalytic site (F82) or involved in Ub interaction (L265 and F182) caused structural changes as shown by molecular dynamics, resulting in a reduction or loss of enzyme activity, respectively. Furthermore, rOtuLi stimulates lipid droplet biogenesis (an inflammatory marker) and induces IL-6 and TNF-a secretion in peritoneal macrophages, both proinflammatory cytokines. Our findings suggest that OtuLi is a cytoplasmic enzyme with K48-linked substrate specificity that could play a part in proinflammatory response in stimulated murine macrophages

Risk assessment of environmental mixture effects

In the environment, organisms are exposed to a diverse array of chemicals in complex mixtures. The majority of approaches that aim to assess the risk of environmental chemical mixtures, including those used by regulatory bodies, use toxicity data generated from the individual component chemicals to predict the overall mixture toxicity. It is assumed that the behaviour of chemicals in a mixture can be predicted using the concepts of concentration or dose addition for chemicals with similar mechanisms of action or response addition for dissimilarly acting chemicals. Based on empirical evidence, most traditional risk assessment methods, such as toxic equivalency factors and the hazard index, make the assumption that the components of a mixture adhere to the concentration addition model. Thus, mixture toxicity can be predicted by the summation of the individual component toxicities. However in some mixtures, interactions can occur between chemicals or at target sites that alter the toxicity so that it is more or less than expected from the constituents. Many regulatory and experimental methods for predicting mixture toxicity rely on the use of a concentration addition model so that if interactions occur in mixtures, the risk posed may have been significantly underestimated. This is particularly concerning when considering environmental mixtures which are often highly complex and composed of indeterminate chemicals. Failure to accurately predict the effects chemicals will have if released into the environment, where they can form mixtures, can lead to unexpected detrimental effects on wildlife and ecosystems. The number of confounding factors that may alter the ecotoxicity of a mixture and the accuracy of predictive methods makes risk assessment of environmental mixtures a complex and intimidating task. With this in mind, this review aims show why accurate risk assessment of mixtures is vital by demonstrating the effect they can have on organisms in the environment. Furthermore, it also aims to look at the current challenges facing the assessment of mixture effects and examines future areas of focus that seek to develop methodologies more suitable for environmental mixtures

Dissecting the structure, thermodynamic stability, and aggregation properties of the A25T transthyretin (A25T-TTR) variant involved in leptomeningeal amyloidosis: identifying protein partners that co-aggregate during A25T-TTR fibrillogenesis in cerebrospinal fluid

Deposition of amorphous aggregates and fibrils of transthyretin (TTR) in leptomeninges and subarachnoid vessels is a characteristic of leptomeningeal amyloidosis (LA), a currently untreatable cerebral angiopathy. Herein, we report the X-ray structure of the A25T homotetramer of TTR, a natural mutant described in a patient with LA. The structure of A25T-TTR is indistinguishable from that of wild-type TTR (wt-TTR), indicating that the difference in amyloidogenicity between A25T-TTR and wt-TTR cannot be ascribed to gross structural differences. Using pressure-induced dissociation of the tetramer, we show that A25T-TTR is 3 kcal/mol less stable than L55P-TTR, the most aggressive mutant of TTR described to date. After incubation for 15 days at 37 °C (pH 7.3), A25T-TTR forms mature amyloid fibrils. To mimic the environment in which TTR aggregates, we investigated aggregation in cerebrospinal fluid (CSF). Unlike L55P-TTR, A25T-TTR rapidly forms amyloid aggregates in CSF that incorporated several protein partners. Utilizing a proteomics methodology, we identified 19 proteins that copurified with A25T-TTR amyloid fibrils. We confirmed the presence of proteins previously identified to be associated with TTR aggregates in biopsies of TTR amyloidosis patients, such as clusterin, apolipoprotein E, and complement proteins. Moreover, we identified novel proteins, such as blood coagulation proteins. Overall, our results revealed the in vitro characterization of TTR aggregation in a biologically relevant environment, opening new avenues of investigation into the molecular mechanisms of LA.CNPqFAPERJCAPE

A core outcome set for neonatal abstinence syndrome: Study protocol for a systematic review, parent interviews and a Delphi survey

Background: The prevalence of neonatal abstinence syndrome (NAS) is increasing globally resulting in an increased incidence of adverse neonatal outcomes and health system costs. Evidence regarding the effectiveness of NAS prevention and management strategies is very weak and further research initiatives are critically needed to support meta-analysis and clinical practice guidelines. In NAS research, the choice of outcomes and the use of valid, responsive and feasible measurement instruments are crucial. There is currently no consensus and evidence-based core outcome set (COS) for NAS. Methods/design: The development of the NAS-COS will include five stages led by an international Multidisciplinary Steering Committee: (1) qualitative interviews with parents/families and a systematic review (SR) to identify items for inclusion in a COS. The SR will also identify participants for the Delphi survey, (2) a three-round Delphi survey to gain expert opinion on the importance of health outcomes influencing NAS management decisions, (3), a consensus meeting to finalize the items and definitions with experts and COS users, (4) feasibility and pilot testing, development of the COS and explanatory document and (5) implementation planning. Discussion: Since standardized outcome measurement and reporting will improve NAS clinical research consistency, efficacy and impact, this COS will reflect the minimum set of health outcomes which should be measured in trials evaluating interventions for preventing or treating NAS

The New Generation Atlas of Quasar Spectral Energy Distributions from Radio to X-rays

We have produced the next generation of quasar spectral energy distributions (SEDs), essentially updating the work of Elvis et al. (1994) by using high-quality data obtained with several space and ground-based telescopes, including NASA's Great Observatories. We present an atlas of SEDs of 85 optically bright, non-blazar quasars over the electromagnetic spectrum from radio to X-rays. The heterogeneous sample includes 27 radio-quiet and 58 radio-loud quasars. Most objects have quasi-simultaneous ultraviolet-optical spectroscopic data, supplemented with some far-ultraviolet spectra, and more than half also have Spitzer mid-infrared IRS spectra. The X-ray spectral parameters are collected from the literature where available. The radio, far-infrared, and near-infrared photometric data are also obtained from either the literature or new observations. We construct composite spectral energy distributions for radio-loud and radio-quiet objects and compare these to those of Elvis et al., finding that ours have similar overall shapes, but our improved spectral resolution reveals more detailed features, especially in the mid and near-infrared.Comment: 46 pages, 10 figures, 10 tables, Accepted by ApJS. Composite SED data files for radio-loud and radio-quiet quasars (rlmsedMR.txt, rqmsedMR.txt) are included in the source (Other formats -> Source). Supplemental figures are not include