Interface entre a política nacional de recursos hídricos e a política nacional de defesa civil, com relação aos desastres hidrológicos

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-graduação em Engenharia AmbientalEstudos do IPCC apontam para o quadro de mudanças climáticas globais e do conseqüente aumento das freqüências dos eventos hidrológicos críticos. As soluções para mitigarem essas mudanças e suas conseqüências devem ser pactuadas em nível global, mas cada país deve atuar, por meio de suas próprias políticas, no sentido de diminuir suas vulnerabilidades. Partiuse do princípio de que o Brasil possui políticas que agem na redução dos efeitos dos desastres, mas estas atuam de forma desarticulada, o que dispensa recursos públicos em soluções paliativas. O atendimento emergencial afeta os gastos sociais dos governos, pois, além dos danos imediatos a serem reparados, há deslocamento das prioridades e de intervenções públicas para demandas de curto prazo, em detrimento dos investimentos de longo prazo e da adoção de estratégias de desenvolvimento sustentável. O objetivo do presente trabalho foi, portanto, buscar interfaces entre a Política Nacional de Recursos Hídricos e a política Nacional de Defesa Civil, com relação aos desastres hidrológicos, no Brasil. Para a busca das interfaces entre ambas as políticas, em um primeiro momento, a Lei das Águas foi dividida em cinco níveis: fundamentos, diretrizes, objetivos, instrumentos e sistemas de gestão. Em um segundo momento, utilizou-se da estratégia para redução de desastres da Secretaria Interinstitucional da Estratégia Internacional para a Redução de Riscos (EIRD)/ONU, que desenvolveu essa metodologia a partir da observação da experiência de diferentes países. Na estratégia da EIRD/ONU, o cruzamento entre as políticas foi feito segundo áreas temáticas, envolvendo os principais aspectos como: compromisso político e desenvolvimento institucional (governabilidade); identificação e avaliação de riscos; gestão do conhecimento; aplicação e instrumentos na gestão de riscos. Constatou-se que para a efetiva implementação, tanto da Política de Recursos Hídricos, quanto da Política de Defesa Civil, necessita-se da interação com outros setores e principalmente com a sociedade. Observou-se coerência nas etapas de Prevenção e Preparação para Emergências, e grande potencial de aproximação entre as estruturas institucionais descentralizadas, como COMDECs/NUDECs e Comitês de Bacias. Os Planos de Bacia, por estarem mais próximos do âmbito local, são os que têm maior potencial de aproximação com os instrumentos da Política Nacional de Defesa Civil. Ao tratar de temas como a prevenção de eventos hidrológicos críticos, os Planos contribuem para a articulação de Políticas, para que as medidas sejam interiorizadas pelos setores. Assim, se ambas as políticas compatibilizarem esforços na prevenção dos efeitos dos desastres hidrológicos, pode-se otimizar ações e até suprir carência de recursos. IPCC reports show the global climate change and the consequent increase of the hidrologically critical events. The solution to reduce theses changes and consequences must be agreed at a global level. However, every country must act on its own policies to reduce its vulnerability. Though Brazil has policies to act on reduction of the disasters effects, various policies are discrete, and public financial resources are spent on temporary solutions. The immediate assistance affects the governmental costs for social aspects. Besides these immediate damages to be repaired, there are displacements of the priorities are disregarded and public interventions to demand of short-coming period in detriment of the investments for the long period and the adoption of strategies for the sustainable development. The objective of the present work was, therefore, to research the interface between the National Policy of Water Resources and the National Policy of Civil Defense in terms of the water-related disasters. At first, the Water Law was divided into five levels: fundamental; lines of direction; objectives; instruments; and management systems. Secondly, the proposal that the International Strategy for Disaster Reduction Secretariat (ISDR/UN) developed from the experiences with different countries. In the strategy of the ISDR/UN, the crossing between the policies was carried out according to thematic areas with main aspects such as: political promises and development, identification and evaluation of risks; knowledge management; and application and instrumentation in risk management. For the effective implementation in both policies, the necessity of the interaction with others sectors and essentially with the society was verified. The coherence in the stages of prevention and preparation of emergencies, and the high potential of approximation between institutional decentralized structures like COMDEC/NUDEC and basin committees were observed. Because of their closeness to the local scope, the Basin Plans are the ones that have higher potential of approaching to the instruments of the National Policy of Civil Defense. On dealing with subjects as the prevention of hidrologically critical events, the Plans contribute to the politicies articulation so that the measures are interiorized by the sectors. Thus, action can be optimized, which can even support the lack of resources if both policies can make compatible efforts on the prevention of the water-related disasters

Atomic force microscopy for single molecule characterisation of protein aggregation.

The development of atomic force microscopy (AFM) has opened up a wide range of novel opportunities in nanoscience and new modalities of observation in complex biological systems. AFM imaging has been widely employed to resolve the complex and heterogeneous conformational states involved in protein aggregation at the single molecule scale and shed light onto the molecular basis of a variety of human pathologies, including neurodegenerative disorders. The study of individual macromolecules at nanoscale, however, remains challenging, especially when fully quantitative information is required. In this review, we first discuss the principles of AFM with a special emphasis on the fundamental factors defining its sensitivity and accuracy. We then review the fundamental parameters and approaches to work at the limit of AFM resolution in order to perform single molecule statistical analysis of biomolecules and nanoscale protein aggregates. This single molecule statistical approach has proved to be powerful to unravel the molecular and hierarchical assembly of the misfolded species present transiently during protein aggregation, to visualise their dynamics at the nanoscale, as well to study the structural properties of amyloid-inspired functional nanomaterials

Structure of a low-population intermediate state in the release of an enzyme product.

Enzymes can increase the rate of biomolecular reactions by several orders of magnitude. Although the steps of substrate capture and product release are essential in the enzymatic process, complete atomic-level descriptions of these steps are difficult to obtain because of the transient nature of the intermediate conformations, which makes them largely inaccessible to standard structure determination methods. We describe here the determination of the structure of a low-population intermediate in the product release process by human lysozyme through a combination of NMR spectroscopy and molecular dynamics simulations. We validate this structure by rationally designing two mutations, the first engineered to destabilise the intermediate and the second to stabilise it, thus slowing down or speeding up, respectively, product release. These results illustrate how product release by an enzyme can be facilitated by the presence of a metastable intermediate with transient weak interactions between the enzyme and product

Educação do campo: o processo de implementação da Casa Familiar Rural do vale do Jaguari (CFR/VJ)

Este texto objetiva socializar uma experiência em Educação do Campo: o processo de implantação da Casa Familiar Rural do Vale do Jaguari – CFR/VJ. Situada na região central do Rio Grande do Sul, a CFR abrange os municípios de Jaguari, Nova Esperança do Sul, Mata e municípios de entorno. Pautada na Pedagogia da Alternância, mostra-se como uma proposta de desenvolvimento capaz de atender às demandas sociais deste grupo que historicamente vem sendo excluído ou submetido a processos educativos que não atendem efetivamente às suas necessidades e expectativas enquanto sujeitos do campo. O presente estudo, de cunho qualitativo, consiste num estudo de caso e fundamenta-se em teóricos da Educação do Campo e do Desenvolvimento Territorial. Deste modo, o artigo faz uma reflexão sobre a Pedagogia da Alternância, os processos de sensibilização e mobilização para a implantação da Casa Familiar Rural do Vale do Jaguari e os resultados, avanços e recuos, em consonância com os aspectos do desenvolvimento territorial.   Palavras-chaves: Casa Familiar Rural; Educação do Campo; Capital Social Desenvolvimento Territorial. DOI: 10.5902/223649941249

Sequence Specificity in the Entropy-Driven Binding of a Small Molecule and a Disordered Peptide

Approximately one-third of the human proteome is made up of proteins that are entirely disordered or that contain extended disordered regions. Although these disordered proteins are closely linked with many major diseases, their binding mechanisms with small molecules remain poorly understood, and a major concern is whether their specificity can be sufficient for drug development. Here, by studying the interaction of a small molecule and a disordered peptide from the oncogene protein c-Myc, we describe a "specific-diffuse" binding mechanism that exhibits sequence specificity despite being of entropic nature. By combining NMR spectroscopy, biophysical measurements, statistical inference, and molecular simulations, we provide a quantitative measure of such sequence specificity and compare it to the case of the interaction of urea, which is diffuse but not specific. To investigate whether this type of binding can generally modify intermolecular interactions, we show that it leads to an inhibition of the aggregation of the peptide. These results suggest that the binding mechanism that we report may create novel opportunities to discover drugs that target disordered proteins in their monomeric states in a specific manner.G.T.H. is supported by the Churchill Scholarship and the Gates Cambridge Trust Scholarship

Structure-Free Validation of Residual Dipolar Coupling and Paramagnetic Relaxation Enhancement Measurements of Disordered Proteins.

Residual dipolar couplings (RDCs) and paramagnetic relaxation enhancements (PREs) have emerged as valuable parameters for defining the structures and dynamics of disordered proteins by nuclear magnetic resonance (NMR) spectroscopy. Procedures for their measurement, however, may lead to conformational perturbations because of the presence of the alignment media necessary for recording RDCs, or of the paramagnetic groups that must be introduced for measuring PREs. We discuss here experimental methods for quantifying these effects by considering the case of the 40-residue isoform of the amyloid β peptide (Aβ40), which is associated with Alzheimer's disease. By conducting RDC measurements over a range of concentrations of certain alignment media, we show that perturbations arising from transient binding of Aβ40 can be characterized, allowing appropriate corrections to be made. In addition, by using NMR experiments sensitive to long-range interactions, we show that it is possible to identify relatively nonperturbing sites for attaching nitroxide radicals for PRE measurements. Thus, minimizing the conformational perturbations introduced by RDC and PRE measurements should facilitate their use for the rigorous determination of the conformational properties of disordered proteins.This is the author accepted manuscript. The final version is available from ACS via http://dx.doi.org/10.1021/acs.biochem.5b0067

A Role of Cholesterol in Modulating the Binding of α-Synuclein to Synaptic-Like Vesicles.

α-Synuclein (αS) is a presynaptic protein whose aggregation is associated with Parkinson's disease (PD). Although the physiological function of αS is still unclear, several lines of evidence indicate that this protein may play a role in the trafficking of synaptic vesicles (SVs) during neurotransmitter release, a task associated with its ability to bind SVs and promote their clustering. It is therefore crucial to identify the cellular factors that modulate this process. To address this question, using nuclear magnetic resonance (NMR) spectroscopy we have characterized the role of cholesterol, a major component of the membrane of SVs, in the binding of αS with synaptic-like vesicles. Our results indicate that cholesterol can act as a modulator of the overall affinity of αS for SVs by reducing the local affinity of the region spanning residues 65-97 in the non-amyloid-β component (NAC) of the protein. The increased population of bound states that expose the region 65-97 to the solvent was found to induce stronger vesicle-vesicle interactions by αS. These results provide evidence that cholesterol modulates the clustering of synaptic vesicles induced by (α)S, and supports the role of the disorder-to-order equilibrium of the NAC region in the modulation of the biological properties of the membrane-bound state of αS

The docking of synaptic vesicles on the presynaptic membrane induced by α-synuclein is modulated by lipid composition.

α-Synuclein (αS) is a presynaptic disordered protein whose aberrant aggregation is associated with Parkinson's disease. The functional role of αS is still debated, although it has been involved in the regulation of neurotransmitter release via the interaction with synaptic vesicles (SVs). We report here a detailed characterisation of the conformational properties of αS bound to the inner and outer leaflets of the presynaptic plasma membrane (PM), using small unilamellar vesicles. Our results suggest that αS preferentially binds the inner PM leaflet. On the basis of these studies we characterise in vitro a mechanism by which αS stabilises, in a concentration-dependent manner, the docking of SVs on the PM by establishing a dynamic link between the two membranes. The study then provides evidence that changes in the lipid composition of the PM, typically associated with neurodegenerative diseases, alter the modes of binding of αS, specifically in a segment of the sequence overlapping with the non-amyloid component region. Taken together, these results reveal how lipid composition modulates the interaction of αS with the PM and underlie its functional and pathological behaviours in vitro

Structure and dynamics of the integrin LFA-1 I-domain in the inactive state underlie its inside-out/outside-in signaling and allosteric mechanisms.

Lymphocyte function-associated antigen 1 (LFA-1) is an integrin that transmits information in two directions across the plasma membrane of leukocytes, in so-called outside-in and inside-out signaling mechanisms. To investigate the structural basis of these mechanisms, we studied the conformational space of the apo I-domain using replica-averaged metadynamics simulations in combination with nuclear magnetic resonance chemical shifts. We thus obtained a free energy landscape that reveals the existence of three conformational substates of this domain. The three substates include conformations similar to existing crystallographic structures of the low-affinity I-domain, the inactive I-domain with an allosteric antagonist inhibitor bound underneath α helix 7, and an intermediate affinity state of the I-domain. The multiple substates were validated with residual dipolar coupling measurements. These results suggest that the presence of three substates in the apo I-domain enables the precise regulation of the binding process that is essential for the physiological function of LFA-1.This study was supported by the Wellcome Trust and the BBSRC.This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.str.2014.12.02