99 research outputs found

    Urban Climate Action. The urban content of the NDCs: Global review 2022

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    This report was prepared by United Nations Human Settlement Programme (UN-Habitat) and the UNESCO Chair on Urban Resilience at the University of Southern Denmark (SDU.Resilience). It offers a global analysis of the urban content of 193 Nationally Determined Contributions (NDCs) submitted to the Secretariat of the United Nations Framework Convention on Climate Change (UNFCCC) before the 19th of June 2022. For this report, more than 200 indicators were used to analyse external data (e.g., Human Development Index and income categorisation) and data within the NDCs, including climate mitigation and adaptation challenges and responses, as well as specific sectors. This analysis is instrumental to supporting Parties’ efforts in further integrating national climate policies and urban climate actions, which is considered fundamental to raising ambition and developing adequate and timely actions as required by the current climate emergency. This review can be instrumental for advocacy and direct support to countries by partner organisations. The work was supported by a group of experts from bilateral and multilateral organisations and academia. Three expert group meetings were convened, and a peer review was organised for the final report

    Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum

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    Different mechanisms have been suggested for cocaine neurotoxicity, including oxidative stress alterations. Nuclear factor kappa B (NF-ÎşB), considered a sensor of oxidative stress and inflammation, is involved in drug toxicity and addiction. NF-ÎşB is a key mediator for immune responses that induces microglial/macrophage activation under inflammatory processes and neuronal injury/degeneration. Although cerebellum is commonly associated to motor control, muscular tone, and balance. Its relation with addiction is getting relevance, being associated to compulsive and perseverative behaviors. Some reports indicate that cerebellar microglial activation induced by cannabis or ethanol, promote cerebellar alterations and these alterations could be associated to addictive-related behaviors. After considering the effects of some drugs on cerebellum, the aim of the present work analyzes pro-inflammatory changes after cocaine exposure. Rats received daily 15 mg/kg cocaine i.p., for 18 days. Reduced and oxidized forms of glutathione (GSH) and oxidized glutathione (GSSG), glutathione peroxidase (GPx) activity and glutamate were determined in cerebellar homogenates. NF-ÎşB activity, CD68, and GFAP expression were determined. Cerebellar GPx activity and GSH/GSSG ratio are significantly decreased after cocaine exposure. A significant increase of glutamate concentration is also observed. Interestingly, increased NF-ÎşB activity is also accompanied by an increased expression of the lysosomal mononuclear phagocytic marker ED1 without GFAP alterations. Current trends in addiction biology are focusing on the role of cerebellum on addictive behaviors. Cocaine-induced cerebellar changes described herein fit with previosus data showing cerebellar alterations on addict subjects and support the proposed role of cerebelum in addiction

    Ultrastructural characterization of human oligodendrocytes and their progenitor cells by pre-embedding immunogold.

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    Oligodendrocytes are the myelinating cells of the central nervous system. They provide trophic, metabolic, and structural support to neurons. In several pathologies such as multiple sclerosis (MS), these cells are severely affected and fail to remyelinate, thereby leading to neuronal death. The gold standard for studying remyelination is the g-ratio, which is measured by means of transmission electron microscopy (TEM). Therefore, studying the fine structure of the oligodendrocyte population in the human brain at different stages through TEM is a key feature in this field of study. Here we study the ultrastructure of oligodendrocytes, its progenitors, and myelin in 10 samples of human white matter using nine different markers of the oligodendrocyte lineage (NG2, PDGFRα, A2B5, Sox10, Olig2, BCAS1, APC-(CC1), MAG, and MBP). Our findings show that human oligodendrocytes constitute a very heterogeneous population within the human white matter and that its stages of differentiation present characteristic features that can be used to identify them by TEM. This study sheds light on how these cells interact with other cells within the human brain and clarify their fine characteristics from other glial cell types

    Formulation and characterization of mucoadhesive controlled release matrix tablets of captopril

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    The purpose of this study is to characterize controlled release matrix tablets of captopril and to find out the physicochemical properties that have an effect on the mucoadhesion process. The hydrophilic matrix tablets contain captopril, microcrystalline cellulose, barium sulfate, ascorbic acid, ethylcellulose N100, hydroxypropylmethylcellulose K15M, talc, magnesium stearate and colloidal silicon dioxide. The physicochemical properties of the formulations have been characterized using confocal microscopy, contact angle, and scanning electron microscopy. The potential mucoadhesion capabilities of the formulations were assessed measuring the surface free energy, the polar and dispersive forces, the spreading coefficients, the surface roughness, and the network structure of the hydrophilic matrix tablets. The results show that when the concentration of HPMC K15M increases, the spreading coefficients of polymer over mucus and mucus over polymer are more positive, thus increasing the contact between the matrix tablets with the mucus layer. The formulation that contains 15% of HPMC K15M is the formulation that presents a greater swelling capacity, a greater increase in surface roughness, and larger pores within the matrix. This formulation has a higher chain mobility and more free macromolecular chains able to diffuse in the mucus layer. Therefore, this formulation has the greatest potential mucoadhesion capability

    Recognizing speculative language in biomedical research articles: a linguistically motivated perspective

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    We explore a linguistically motivated approach to the problem of recognizing speculative language (“hedging”) in biomedical research articles. We describe a method, which draws on prior linguistic work as well as existing lexical resources and extends them by introducing syntactic patterns and a simple weighting scheme to estimate the speculation level of the sentences. We show that speculative language can be recognized successfully with such an approach, discuss some shortcomings of the method and point out future research possibilities.

    The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression

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    The SeDeM Diagram Expert System has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril Direct Compression SR Matrix Tablets. The application of the Sedem Diagram Expert System enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM Diagram Expert System as system responses

    RNA-binding properties and membrane insertion of Melon necrotic spot virus (MNSV) double gene block movement proteins

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    Advances in structural and biochemical properties of carmovirus movement proteins (MPs) have only been obtained in p7 and p9 from Carnation mottle virus (CarMV). Alignment of carmovirus MPs revealed a low conservation of amino acid identity but interestingly, similarity was elevated in regions associated with the functional secondary structure elements reported for CarMV which were conserved in all studied proteins. Nevertheless, some differential features in relation with CarMV MPs were identified in those from Melon necrotic virus (MNSV) (p7A and p7B). p7A was a soluble non-sequence specific RNA-binding protein, but unlike CarMV p7, its central region alone could not account for the RNA-binding properties of the entire protein. In fact, a 22-amino acid synthetic peptide whose sequence corresponds to this central region rendered an apparent dissociation constant (K(d)) significantly higher than that of the corresponding entire protein (9 mM vs. 0.83-25.7 microM). This p7A-derived peptide could be induced to fold into an alpha-helical structure as demonstrated for other carmovirus p7-like proteins. Additionally, in vitro fractionation of p7B transcription/translation mixtures in the presence of ER-derived microsomal membranes strongly suggested that p7B is an integral membrane protein. Both characteristics of these two small MPs forming the double gene block (DGB) of MNSV are discussed in the context of the intra- and intercellular movement of carmovirus

    Structure-based statistical analysis of transmembrane helices

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    Recent advances in determination of the high-resolution structure of membrane proteins now enable analysis of the main features of amino acids in transmembrane (TM) segments in comparison with amino acids in water-soluble helices. In this work, we conducted a large-scale analysis of the prevalent locations of amino acids by using a data set of 170 structures of integral membrane proteins obtained from the MPtopo database and 930 structures of water-soluble helical proteins obtained from the protein data bank. Large hydrophobic amino acids (Leu, Val, Ile, and Phe) plus Gly were clearly prevalent in TM helices whereas polar amino acids (Glu, Lys, Asp, Arg, and Gln) were less frequent in this type of helix. The distribution of amino acids along TM helices was also examined. As expected, hydrophobic and slightly polar amino acids are commonly found in the hydrophobic core of the membrane whereas aromatic (Trp and Tyr), Pro, and the hydrophilic amino acids (Asn, His, and Gln) occur more frequently in the interface regions. Charged amino acids are also statistically prevalent outside the hydrophobic core of the membrane, and whereas acidic amino acids are frequently found at both cytoplasmic and extra-cytoplasmic interfaces, basic amino acids cluster at the cytoplasmic interface. These results strongly support the experimentally demonstrated biased distribution of positively charged amino acids (that is, the so-called the positive-inside rule) with structural data

    A multi-component flood risk assessment in the Maresme coast (NW Mediterranean)

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    Coastal regions are the areas most threatened by natural hazards, with floods being the most frequent and significant threat in terms of their induced impacts, and therefore, any management scheme requires their evaluation. In coastal areas, flooding is a hazard associated with various processes acting at different scales: coastal storms, flash floods, and sea level rise (SLR). In order to address the problem as a whole, this study presents a methodology to undertake a preliminary integrated risk assessment that determines the magnitude of the different flood processes (flash flood, marine storm, SLR) and their associated consequences, taking into account their temporal and spatial scales. The risk is quantified using specific indicators to assess the magnitude of the hazard (for each component) and the consequences in a common scale. This allows for a robust comparison of the spatial risk distribution along the coast in order to identify both the areas at greatest risk and the risk components that have the greatest impact. This methodology is applied on the Maresme coast (NW Mediterranean, Spain), which can be considered representative of developed areas of the Spanish Mediterranean coast. The results obtained characterise this coastline as an area of relatively low overall risk, although some hot spots have been identified with high-risk values, with flash flooding being the principal risk process
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