Total synthesis and stereochemical assignment of miharamycins

Tese de doutoramento, Química (Química Orgânica), 2009, Universidade de Lisboa, Faculdade de CiênciasDisponível no documentoFundação para Ciência e Tecnologia (SFRH/BD/17775/2004

Potenciais implicações dos conflitos no bem-estar no trabalho, na satisfação profissional e no desempenho contextual

Dissertação de Mestrado em Psicologia Social e das Organizações apresentada ao ISPA - Instituto UniversitárioAs organizações encontram-se estruturadas com base em grupos de trabalho que interagem entre si com vista ao alcance de objetivos comuns. O potencial do trabalho e do desenvolvimento de um grupo são, também, função dos seus aspetos emocionais e do modo como, muitas vezes, o grupo gere as situações conflituais com que se vê confrontado ao longo da sua existência. Deste modo, a presente investigação procurou compreender as potenciais implicações que os conflitos organizacionais podem ter no Bem-estar laboral, na Satisfação Profissional e no Desempenho Contextual dos indivíduos. Com uma amostra de 132 participantes, este estudo utilizou o Questionário de Ambiente de Trabalho para avaliar os Conflitos (Vicente & D' Oliveira, 2012), para medir o BET a versão portuguesa da UWES de Schaufeli e Bakker (2003), para medir a Satisfação Profissional a escala de Lima, Vala e Monteiro (1994), e por fim, para medir o Desempenho Contextual utilizaram-se 15 itens propostos pelos autores Motowidlo e Van Scotter (1994) e traduzidos posteriormente por Alves e D’ Oliveira (2013). Os resultados pretenderam explorar o efeito mediador que o bem-estar no trabalho e a satisfação profissional exercem sobre a relação entre os conflitos e o desempenho contextual. Para o efeito, recorreu-se à análise de regressões lineares múltiplas, tendo sido verificado o modelo de investigação proposto. Foi obtido um efeito mediador do bem-estar no trabalho e da satisfação profissional na relação entre os conflitos e o desempenho contextual.ABSTRACT: Organizations are structured so that work groups can interact among themselves in order to achieve common goals. The groups work potencial and development depends directly on the way in which the group manages conflicts throughout its existence. This investigations purpose is to understand the implications that organizational conflicts can have on the labor well-being, job satisfaction and on the subjects contextual performance. With a sample of 132 individuals this study used the “Questionário de ambiente de trabalho” to evaluate the conflicts (Vicente & D' Oliveira, 2012). To measure the BET we used the Portuguese version of UWES (Schaufeli & Bakker, 2003). To measure the job satisfaction we used the (Lima, Vala, and Monteiro (1994) scale. And, finally, to measure the contextual performance we used 15 items proposed by Motowidlo and Van Scotter (1994) and translated by Alves and D`Oliveira (2013). The purpose of the results is to explore the mediating effect that the labor well-being and professional satisfaction have on the relation between conflict and contextual performance. In order to do this I used a multiple linear regressions analysis and the proposed model of investigation was verified. I obtained mediating effect of labor well-being and professional satisfaction in the relation between conflicts and contextual performance

Socio-emotional skills profiles and their relations with career exploration and perceived parental support among 8th grade students

Socio-emotional skills can play a crucial role in students career development. This study used a person-centered approach to explore socio-emotional skills (curiosity, optimism, empathy, sociability, and responsibility) profiles among 8 degrees grade students (N = 310). We also explored the relations of these profiles with career exploration (self and environmental), perceived parental support (emotional support, instrumental assistance, career-related modeling, and verbal encouragement) and school achievement. Using Latent Profile Analysis (LPA), four distinct profiles emerged that differed in terms of level and shape, namely: Other and Task oriented profile, Socio-emotional Adaptive profile, Socio-emotional non-Adaptive profile, Self- Oriented profile. Our results show that the "Socio-emotional Adaptive" profile can be clearly differentiated from the "Socio-emotional non-Adaptive" profile given the higher values it presents regarding all the variables in study. However, the differences between the "Other and Task Oriented" profile and "Self-Oriented" profile (intermediate profiles) were analyzed and discussed from qualitative point-of-view and adopting an exploratory approach. Overall, the findings of this study indicate that socio-emotional profiles have the potential to account for variations in career behaviors and academic performance. These results provide valuable insights for the development and implementation of career-oriented interventions targeted at 8th grade students and their immediate relational environments.info:eu-repo/semantics/publishedVersio

Glyco-Tools to Crack Unsolved Biomedical Needs

CA18132publishersversionpublishe

Molecular Recognition Insights of Sialic Acid Glycans by Distinct Receptors Unveiled by NMR and Molecular Modeling

IF/ 00780/2015 PTDC/BIA-MIB/31028/2017 UIDP/04378/2020 UIDB/04378/2020 LA/P/0140/2020 SFRH/BD/140394/2018 2020.03261. CEECIND CA18132 PID 2019-107770RA-I00 H2020-MSCA-ITN-2020 agency for the Glytunes project (956758).All cells are decorated with a highly dense and complex structure of glycan chains, which are mostly attached to proteins and lipids. In this context, sialic acids are a family of nine-carbon acidic monosaccharides typically found at the terminal position of glycan chains, modulating several physiological and pathological processes. Sialic acids have many structural and modulatory roles due to their negative charge and hydrophilicity. In addition, the recognition of sialic acid glycans by mammalian cell lectins, such as siglecs, has been described as an important immunological checkpoint. Furthermore, sialic acid glycans also play a pivotal role in host–pathogen interactions. Various pathogen receptors exposed on the surface of viruses and bacteria are responsible for the binding to sialic acid sugars located on the surface of host cells, becoming a critical point of contact in the infection process. Understanding the molecular mechanism of sialic acid glycans recognition by sialic acid-binding proteins, present on the surface of pathogens or human cells, is essential to realize the biological mechanism of these events and paves the way for the rational development of strategies to modulate sialic acid-protein interactions in diseases. In this perspective, nuclear magnetic resonance (NMR) spectroscopy, assisted with molecular modeling protocols, is a versatile and powerful technique to investigate the structural and dynamic aspects of glycoconjugates and their interactions in solution at the atomic level. NMR provides the corresponding ligand and protein epitopes, essential for designing and developing potential glycan-based therapies. In this review, we critically discuss the current state of knowledge about the structural features behind the molecular recognition of sialic acid glycans by different receptors, naturally present on human cells or pathogens, disclosed by NMR spectroscopy and molecular modeling protocols.publishersversionpublishe

Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies

COMPETE Programme: SAICTPAC/0019/2015 IF/00780/2015 Project no. 022161Monocationic and dicationic cholinium ionic liquids (ILs) were synthesized and evaluated as acetylcholinesterase (AChE) inhibitors with in vitro and in silico models, and their cytotoxicity was assessed using human cell lines from skin (CRL-1502) and colon cancer (CaCo-2). The ILs with a longer alkyl chain were stronger AChE inhibitors, the dicationic ILs (DILs) being more active than the monocationic ILs. The best result was obtained for [N1,1,12,2(OH)]2Br2 at a concentration of 0.18 μM by reducing half enzyme activity without affecting the viability of tested cell lines. A saturation-transfer difference NMR (STD-NMR) binding study was carried out, demonstrating that [N1,1,12,2(OH)]2Br2 binds to AChE. STD-NMR competition binding experiments, using galanthamine as a reference ligand, clearly highlight that the IL displaces galanthamine in the AChE binding site pinpointing [N1,1,12,2(OH)]2Br2 inside the deep gorge of AChE. In order to obtain a three-dimensional (3D) view of the molecular recognition process, in silico molecular docking studies on the active site of AChE were carried out. The proposed 3D model of the AChE/DIL complex is in agreement with the STD-derived epitope mapping, which explains the competition with galanthamine and unveils key interactions in both peripheral and catalytic sites of AChE. These interactions seem essential to govern the recognition of DILs by the AChE enzyme. Our study provides a structural and functional platform that can be used for the rational design of choline-based ILs as potent AChE inhibitors.publishersversionpublishe

Beyond a Fluorescent Probe: Inhibition of Cell Division Protein FtsZ by mant-GTP Elucidated by NMR and Biochemical Approaches

© 2015 American Chemical Society. FtsZ is the organizer of cell division in most bacteria and a target in the quest for new antibiotics. FtsZ is a tubulin-like GTPase, in which the active site is completed at the interface with the next subunit in an assembled FtsZ filament. Fluorescent mant-GTP has been extensively used for competitive binding studies of nucleotide analogs and synthetic GTP-replacing inhibitors possessing antibacterial activity. However, its mode of binding and whether the mant tag interferes with FtsZ assembly function were unknown. Mant-GTP exists in equilibrium as a mixture of C2′- and C3′-substituted isomers. We have unraveled the molecular recognition process of mant-GTP by FtsZ monomers. Both isomers bind in the anti glycosidic bond conformation: 2′-mant-GTP in two ribose puckering conformations and 3′-mant-GTP in the preferred C2′ endo conformation. In each case, the mant tag strongly interacts with FtsZ at an extension of the GTP binding site, which is also supported by molecular dynamics simulations. Importantly, mant-GTP binding induces archaeal FtsZ polymerization into inactive curved filaments that cannot hydrolyze the nucleotide, rather than straight GTP-hydrolyzing assemblies, and also inhibits normal assembly of FtsZ from the Gram-negative bacterium Escherichia coli but is hydrolyzed by FtsZ from Gram-positive Bacillus subtilis. Thus, the specific interactions provided by the fluorescent mant tag indicate a new way to search for synthetic FtsZ inhibitors that selectively suppress the cell division of bacterial pathogens.BFU2011-23416 and BFU2014-51823-R (J.M.A), CTQ2012-32065 (J.J.B.), CM 2010/BMD-2353 (J.J.B. and J.M.A.), FCT SFRH/BPD/65462/2009 and UID/Multi/04378/2013 (F.M.) and a FPI fellowship (L.B.R.A).Peer Reviewe

Os Lusíadas de Luís de Camões comentados por D. Marcos de S. Lourenço

info:eu-repo/semantics/publishedVersio

Letter to the Editor: Medication-Overuse Headache is Common in Portuguese Migraineurs

Carta ao Editor: A Cefaleia por Uso Excessivo de Medicação é Comum em Doentes Portugueses com Enxaquecapublishersversionpublishe