Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.

PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils

Ensaio de competição de cultivares convencionais da rede soja sul de pesquisa, safra 2009/10.

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Desempenho de Cultivares de Soja Transgênica (Intacta e Rr1) na Macrorregião Sojícola 1, Avaliadas na Safra 2013/14 ela Rede Soja Sul de Pesquisa.

A Rede Soja Sul de Pesquisa, composta por empresas de melhoramento e de pesquisa (CCGL Tecnologia, Coodetec, GDM Genética do Brasil, Embrapa Clima Temperado, Embrapa Trigo, Fepagro, Geneze Sementes, Nidera Sementes, Syngenta Seeds, TMG, Instituto Federal de Sertão e Fundação Pró-Sementes), conduz ensaios que avaliam, no mesmo ambiente e manejo, o desempenho agronômico de cultivares registradas por diferentes obtentores. Assim, o objetivo deste trabalho foi avaliar o rendimento de grãos de cultivares de soja das tecnologias Intacta e RR1, em ambientes da Macrorregião sojícola 1

Identification and relative quantification of tyrosine nitration in a model peptide using two-dimensional infrared spectroscopy

Nitration of tyrosine in proteins and peptides is a post-translational modification that occurs under conditions of oxidative stress. It is implicated in a variety of medical conditions, including neurodegenerative and cardiovascular diseases. However, monitoring tyrosine nitration and understanding its role in modifying biological function remains a major challenge. In this work, we investigate the use of electron-vibration-vibration (EVV) two-dimensional infrared (2DIR) spectroscopy for the study of tyrosine nitration in model peptides. We demonstrate the ability of EVV 2DIR spectroscopy to differentiate between the neutral and deprotonated states of 3-nitrotyrosine, and we characterize their spectral signatures using information obtained from quantum chemistry calculations and simulated EVV 2DIR spectra. To test the sensitivity of the technique, we use mixed-peptide samples containing various levels of tyrosine nitration, and we use mass spectrometry to independently verify the level of nitration. We conclude that EVV 2DIR spectroscopy is able to provide detailed spectroscopic information on peptide side-chain modifications and to detect nitration levels down to 1%. We further propose that lower nitration levels could be detected by introducing a resonant Raman probe step to increase the detection sensitivity of EVV 2DIR spectroscopy. (Graph Presented)

Ensaio de competição de cultivares tolerantes ao glifosato da rede soja sul de pesquisa, safra 2009/10.

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Molecular Interpretation of ACTH-β-Endorphin Coaggregation: Relevance to Secretory Granule Biogenesis

Peptide/protein hormones could be stored as non-toxic amyloid-like structures in pituitary secretory granules. ACTH and β-endorphin are two of the important peptide hormones that get co-stored in the pituitary secretory granules. Here, we study molecular interactions between ACTH and β-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-β-endorphin aggregate, ACTH alone cannot aggregate into amyloid under various plausible conditions. Using all atom molecular dynamics simulation we investigate the early molecular interaction events in the ACTH-β-endorphin system, β-endorphin-only system and ACTH-only system. We find that β-endorphin and ACTH formed an interacting unit, whereas negligible interactions were observed between ACTH molecules in ACTH-only system. Our data suggest that ACTH is not only involved in interaction with β-endorphin but also enhances the stability of mixed oligomers of the entire system

Permanent Campaigning: A Meta-Analysis and Framework for Measurement

Permanent campaigning emerged as a concept in the 1970s in studies of US politics but is now recognized as a universal phenomenon. Despite its long history, there has been no attempt to build a holistic picture of the elements that constitute a permanent campaign. Generally, researchers focus on tactical elements, situating their use within an overall strategy, but there is a lack of a broader methodological framework for holistically measuring adherence to the permanent campaigning. This article presents results of a meta-analysis of relevant research to provide a framework to understand how permanent campaigning is practiced. Our study showed there were three reasonably discrete forms of campaigning activities that had been identified: those in which permanent campaign strategies are related to capacity building and strategy; a second, in which permanent campaigning relates to paid and owned media; and a third in which earned media is the main focus. In mapping these studies, we identify the common features of permanent campaigning, identifying strong and weak indicators and the extent these are employed by the government, parties, or elected representatives and within which political systems: parliamentarism or presidentialism. Our framework can be applied in future comparative research to understand trends in political communication

Genetic improvement of soybeans in Brazil: South and Midwest regions

Abstract: Soybean [Glycine max (L.) Merril] is one of the main crops produced worldwide, and on-farm yields have increased considerably in the last decades in Brazil. We evaluated the genetic gain for agronomic, phenological, and end-use quality traits in 29 cultivars in the South Region, and in 38 cultivars in the Midwest Region in Brazil, released from 1966 to 2011. Field trials were conducted in Macroregions 1, 2, and 4, in 2016?2017, 2017?2018, and 2018?2019 crop seasons. The best linear unbiased predictors (BLUP) of the cultivars were obtained for each trait using a linear model. The BLUPs were regressed with the year of release using linear and quadratic regression models. The rates of genetic gain for seed yield ranged from 11.98 to 15.31 kg ha?1 yr?1 (0.33 to 0.42% yr?1) in the South Region, and from 13.58 to 21.84 kg ha?1 yr?1 (0.47 to 0.77% yr?1) in the Midwest Region. New cultivars presented taller plants and more seed oil content, oil and protein yield, and lower seed weight, days to flowering, days to maturity, and seed protein content than old cultivars in the South Region, although with differences between the Macroregions. In the Midwest Region, new cultivars showed higher seed oil content, oil and protein yield, and lower bottom pod height and seed protein content than old cultivars. Our results showed that breeding programs have been efficient to improve soybean yield and other traits across the years, without yield plateaus in sight