S-Nitrosothiols: Electronic Structure and Substituent Effects

S-nitrosothiols (RSNOs) are biologically important molecules involved in the storage and transport of nitric oxide (NO) and account for much of its signaling activity in living organisms. RSNOs have significant impact on NO signaling through, S-nitrosation, a major post-translational modification of proteins. These unstable thiol derivatives readily undergo homolytic dissociation of the S–N bond to release NO. RSNOs have potential therapeutic applications as NO donors, although the development of novel RSNOs has been slow due to the complex electronic structure of the –SNO group. A specific focus on the impact of the –R group on RSNO properties via substituent effect study, should serve as a reliable means for systematic development of new RSNOs. In this work, electronic structure calculations have been used to investigate substituent effects in RSNOs. A library of substituents was developed for substitution in several RSNO models, with emphasis on aromatic RSNOs (ArSNOs). Para-substituted PhSNOs showed a significant substituent effect despite the lack of conjugation between the –SNO group and substituent due to the non-planar nature of the –SNO group with the aromatic ring. A thorough computational study of PhSNO as the parent ArSNO revealed the primary mode of substituent effect, a novel cascading double conjugation. This conjugation motif involves the long-range delocalization of electron density from the oxygen lone pair to σSN* orbital and then to the phenyl ring π-system, effectively connecting the –SNO group and substituent positions of the aromatic ring. Detailed analysis of vinyl-substituted RSNO (VinSNO) was performed to further understand the fundamental interaction of a π-system with an adjacent –SNO group. The impact of the vinyl π-bond on the adjacent –SNO group of VinSNO again revealed cascading double conjugation as the dominant feature. In general, cascading double conjugation will effectively destabilize the S–N bond in ArSNOs, specifically those RSNOs with a π-system adjacent to the –SNO group. Computational study of PhSNO and VinSNO was also carried out using Lewis acids and external electric fields (EEFs) to explore their effect on the –SNO group as well as the cascading double conjugation. Application of both resulted in substantial modulation of the –SNO group properties. Furthermore, use of Lewis acids or EEF, in tandem with select substituents, is expected to improve the functionality of ArSNOs as NO donors and advance the development of novel RSNOs

The impact of wheat market liberalization on the seed industry’s innovative capacity: an assessment of Brazil’s experience

Market liberalization has a profound impact on the structure of economies as well as changes the roles of the public and private sectors and affects innovative capacity of countries. This paper explores the Brazilian experience with wheat market liberalization and the impact on the seed sector. The analysis presented in this paper is based on interviews with 12 experts intimately involved in wheat research and breeding in Brazil. The analysis reveals liberalization boosted private investment in wheat R&D, which translated into increased research output. However, Brazil faced many challenges in establishing wheat innovation system and important lessons can be drawn from its experience

Structure, Stability, and Substituent Effects in Aromatic \u3cem\u3eS\u3c/em\u3e-Nitrosothiols: The Crucial Effect of a Cascading Negative Hyperconjugation/Conjugation Interaction

Aromatic S-nitrosothiols (RSNOs) are of significant interest as potential donors of nitric oxide and related biologically active molecules. Here, we address a number of poorly understood properties of these species via a detailed density functional theory and the natural bond orbital (NBO) investigation of the parent PhSNO molecule. We find that the characteristic perpendicular orientation of the −SNO group relative to the phenyl ring is determined by a combination of the steric factors and the donor–acceptor interactions including, in particular, a cascading orbital interaction involving electron delocalization from the oxygen lone pair to the σ-antibonding S–N orbital and then to the π*-aromatic orbitals, an unusual negative hyperconjugation/conjugation long-range delocalization pattern. These interactions, which are also responsible for the relative weakness of the S–N bond in PhSNO and the modulation of −SNO group properties in substituted aromatic RSNOs, can be interpreted as a resonance stabilization of the ionic resonance component RS–/NO+ of the RSNO electronic structure by the aromatic ring, similar to the resonance stabilization of PhS– anion. These insights into the chemistry and structure–property relationships in aromatic RSNOs can provide an important theoretical foundation for rational design of new RSNOs for biomedical applications

Generation of Molecular Complexity from Cyclooctatetraene: Preparation of Aminobicyclo[5.1.0]octitols

A series of eight stereoisomeric N-(tetrahydroxy bicyclo-[5.1.0]oct-2S*-yl)phthalimides were prepared in one to four steps from N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide (±)-7, which is readily available from cyclooctatetraene (62 % yield). The structural assignments of the stereoisomers were established by 1H NMR spectral data as well as X-ray crystal structures for certain members. The outcomes of several epoxydiol hydrolyses, particularly ring contraction and enlargement, are of note. The isomeric phthalimides as well as the free amines did not exhibit β-glucosidase inhibitory activity at a concentration of less than 100 μM

Einfluss modifizierter Herz-Lungen-Maschinen-Systeme sowie einer selektiven Perfusion der Lungenstrombahn zur Verminderung der inflammatorischen Reaktion nach herzchirurgischen Operationen im Vergleich zum OPCAB-Verfahren

Pulmonary TNFa concentration and wall thickness after on- versus off pump cardiac surger

Disputas semânticas sobre igualdade e família(s)

This paper aims to understand the discursive strategies and morality that are mobilized in the scope of Legislative and Judiciary performance regarding the regulation of gay and lesbian marriages. In order to do so, we analyzed some judicial decisions and legislative proposals that deal with the (non) recognition of these marriages as family entities. Such material was analyzed in accordance with the anthropological perspective of the recognition demands. From the mapping of concepts and arguments activated by the various subjects involved, it is revealed the polysemy that certain terms such as "family" and "equality" assume.O presente trabalho visa compreender as estratégias discursivas e as moralidades que são mobilizadas no âmbito da atuação do Legislativo e do Judiciário quanto à regulamentação das conjugalidades de gays e de lésbicas. Para tanto, toma-se como objeto de análise alguns julgados e projetos de lei que tratam acerca do (não) reconhecimento dessas conjugalidades enquanto entidade familiar e busca-se analisar esse material em consonância com alguns apontamentos de uma perspectiva antropológica das demandas de reconhecimento. A partir do mapeamento dos conceitos e argumentos acionados pelos diversos sujeitos envolvidos, desvela-se a polissemia que certos termos como “família” e “igualdade” assumem

Home country effects of offshoring. A critical survey on empirical literature.

The International fragmentation of production processes is of rising importance. One part of this fragmentation involves the relocation of a production process from a home- to a new host country. This literature survey deals with the effects of such relocations on the home country. First of all, we try to conceptualize the terms and definitions most frequently used in this context which are "outsourcing", "offshore outsourcing" and "offshoring". Despite the fact that there is little textual documentation dealing directly with the phenomena of offshoring and offshore outsourcing we try to give an overview of possible empirical literature to which one can regard to. Including FDI literature we try to cover empirical literature which can provide helpful insight on the effects of a relocation to foreign countries on the home country in connection with wages, skill upgrading, prices, profits, taxes and unions. (author's abstract)Series: Discussion Papers SFB International Tax Coordinatio

Brain development in the yellow fever mosquito Aedes aegypti: a comparative immunocytochemical analysis using cross-reacting antibodies from Drosophila melanogaster

Considerable effort has been directed towards understanding the organization and function of peripheral and central nervous system of disease vector mosquitoes such as Aedes aegypti. To date, all of these investigations have been carried out on adults but none of the studies addressed the development of the nervous system during the larval and pupal stages in mosquitoes. Here, we first screen a set of 30 antibodies, which have been used to study brain development in Drosophila, and identify 13 of them cross-reacting and labeling epitopes in the developing brain of Aedes. We then use the identified antibodies in immunolabeling studies to characterize general neuroanatomical features of the developing brain and compare them with the well-studied model system, Drosophila melanogaster, in larval, pupal, and adult stages. Furthermore, we use immunolabeling to document the development of specific components of the Aedes brain, namely the optic lobes, the subesophageal neuropil, and serotonergic system of the subesophageal neuropil in more detail. Our study reveals prominent differences in the developing brain in the larval stage as compared to the pupal (and adult) stage of Aedes. The results also uncover interesting similarities and marked differences in brain development of Aedes as compared to Drosophila. Taken together, this investigation forms the basis for future cellular and molecular investigations of brain development in this important disease vecto

The ​ ​representation ​ ​of ​ ​refuge ​ ​and ​ ​migration ​ ​in ​ ​the ​ ​online ​ ​media ​ ​in ​ ​Brazil ​ ​and abroad: ​ ​a ​ ​Cognitive ​ ​Linguistics ​ ​analysis

The present study aims at mapping how the situation of refuge and migration is represented metaphorically in the Brazilian online media. From the data collected, we will establish comparisons between the representations that were found. An approach that contemplates the frame study employed in the media allows us to observe that verbal and nonverbal resources, metaphorical sentences and lexical items are constituted into discursive ​frames. ​We intend to discuss how the migrant and the refugee are represented in the Brazilian online media. Some questions we will investigate are: What are the discourses on the reception of refugees and migrants? Which discourses on the integration of refugees and migrants are broadcasted? From these questions, we will examine how such categories compose the image of the migrant and the refugee. The corpus used was based on the news of the online newspaper ​Folha de São Paulo from June, 2015, seen as it was in this month that the so called “refugee crisis” occurred in Europe. The gathering and analysis were done with the help of two free softwares: Notepad++, that allows the user to save texts in ​txt format, and Antconc, that enables the analysis of several txt files through tools that are used in Corpus Linguistics. The concordance lines obtained by inserting a word of choice in AntConc’s concordancer were then analyzed manually through Cameron’s (2010) Metaphor-led Discourse Analysis. A larger objective will be to identify which metaphorical ​frames are used in the migrant’s and refugee’s media representation and what are their social implications. Such frames contribute to organize and potentialize the discourse about the ​ ​Other ​ ​(BRUNO, ​ ​2016)

Fucoxanthin, A Carotenoid Derived from Phaeodactylum tricornutum Exerts Antiproliferative and Antioxidant Activities In Vitro

Microalgae contain a multitude of nutrients and can be grown sustainably. Fucoxanthin, a carotenoid from Phaeodactylum tricornutum, could have beneficial health effects. Therefore, we investigated the anti-inflammatory, antioxidative and antiproliferative effects of fucoxanthin derived from this diatom in vitro. The effects of purified fucoxanthin on metabolic activity were assessed in blood mononuclear cells and different cell lines. In cell lines, caspase 3/7 activity was also analyzed. Nitrogen monoxide release and mRNA-expression of proinflammatory cytokines were measured. For antioxidant assays, cell free assays were conducted. Additionally, the antioxidant effect in neutrophils was quantified and glutathione was determined in HeLa cells. The results show that neither did fucoxanthin have anti-inflammatory properties nor did it exert cytotoxic effects on mononuclear cells. However, the metabolic activity of cell lines was decreased up to 58% and fucoxanthin increased the caspase 3/7 activity up to 4.6-fold. Additionally, dose-dependent antioxidant effects were detected, resulting in a 63% decrease in chemiluminescence in blood neutrophils and a 3.3-fold increase in the ratio of reduced to oxidized glutathione. Our studies show that fucoxanthin possesses antiproliferative and antioxidant activities in vitro. Hence, this carotenoid or the whole microalgae P. tricornutum could be considered as a food or nutraceutical in human nutrition, showcasing beneficial health effects