847 research outputs found

    Localized recruitment and activation of RhoA underlies dendritic spine morphology in a glutamate receptor–dependent manner

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    Actin is the major cytoskeletal source of dendritic spines, which are highly specialized protuberances on the neuronal surface where excitatory synaptic transmission occurs (Harris, K.M., and S.B. Kater. 1994. Annu. Rev. Neurosci. 17:341–371; Yuste, R., and D.W. Tank. 1996. Neuron. 16:701–716). Stimulation of excitatory synapses induces changes in spine shape via localized rearrangements of the actin cytoskeleton (Matus, A. 2000. Science. 290:754–758; Nagerl, U.V., N. Eberhorn, S.B. Cambridge, and T. Bonhoeffer. 2004. Neuron. 44:759–767). However, what remains elusive are the precise molecular mechanisms by which different neurotransmitter receptors forward information to the underlying actin cytoskeleton. We show that in cultured hippocampal neurons as well as in whole brain synaptosomal fractions, RhoA associates with glutamate receptors (GluRs) at the spine plasma membrane. Activation of ionotropic GluRs leads to the detachment of RhoA from these receptors and its recruitment to metabotropic GluRs. Concomitantly, this triggers a local reduction of RhoA activity, which, in turn, inactivates downstream kinase RhoA-specific kinase, resulting in restricted actin instability and dendritic spine collapse. These data provide a direct mechanistic link between neurotransmitter receptor activity and the changes in spine shape that are thought to play a crucial role in synaptic strength

    On The Mechanism Of The Aza-morita-baylis-hillman Reaction: Esi-ms Interception Of A Unique New Intermediate.

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    Solutions of aza-Morita-Baylis-Hillman (aza-MBH) reactions were directly monitored by ESI(+)-MS(/MS) spectrometry to obtain information on their mechanism. A unique bis-sulfonamide intermediate was intercepted and characterized and, based on this novel species, a mechanism that rationalizes the uniqueness of aza-MBH reactions is proposed.476593-

    The Action of Polyphenols in Diabetes Mellitus and Alzheimer's Disease: A Common Agent for Overlapping Pathologies

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    Diabetes Mellitus (DM) and Alzheimer's disease (AD) are two prevalent diseases in modern societies, which are caused mainly by current lifestyle, aging and genetic alterations. It has already been demonstrated that these two diseases are associated, since individuals suffering from DM are prone to develop AD. Conversely, it is also known that individuals with AD are more susceptible to DM, namely type 2 diabetes (T2DM). Therefore, these two pathologies, although completely different in terms of symptomatology, end up sharing several mechanisms at the molecular level, with the most obvious being the increase of oxidative stress and inflammation. Polyphenols are natural compounds widely spread in fruits and vegetables whose dietary intake has been considered inversely proportional to the incidence of DM and AD. So, it is believed that this group of phytochemicals may have preventive and therapeutic potential, not only by reducing the risk and delaying the development of these pathologies, but also by improving brain's metabolic profile and cognitive function. The aim of this review is to understand the extent to which DM and AD are related pathologies, the degree of similarity and the relationship between them, to detail the molecular mechanisms by which polyphenols may exert a protective effect, such as antioxidant and anti-inflammatory effects, and highlight possible advantages of their use as common preventive and therapeutic alternatives.info:eu-repo/semantics/publishedVersio

    MALDI imaging mass spectrometry of fresh water cyanobacteria: spatial distribution of toxins and other metabolites

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    Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Cyanobacteria are among the most ancient forms of life, yet they are known to synthesize highly sophisticated defense molecules, such as the highly hepatotoxic cyclic peptides microcystins and nodularins produced by the genera Microcystis, Anabaena and Nodularia. These metabolites are released by cyanobacteria to water environments causing episodes of fatalities among animals and humans. To better understand the releasing of these metabolites, imaging mass spectrometry (IMS) using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) was herein applied to determine the spatial distribution of such toxins directly on agar-based cultures. Other key metabolites such as aeruginosin 602 and the siderophore anachelin were also mapped in mixed cyanobacterial cultures, showing the great potential of IMS to spatially monitor the biochemical details of cyanobacterial defense and interactions.Cyanobacteria are among the most ancient forms of life, yet they are known to synthesize highly sophisticated defense molecules, such as the highly hepatotoxic cyclic peptides microcystins and nodularins produced by the genera Microcystis, Anabaena and No284521528FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)sem informaçãosem informaçãosem informaçã

    Occurrence, nanofiltration treatment and toxicity screening

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    Funding Information: This work was also funded by Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior ( FCT / MCTES , Portugal) through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020) and the Associate Laboratory LS4FUTURE (LA/P/0087/2020). Teresa I.A. Gouveia and Vanessa Jorge Pereira would like to thank the Portuguese Foundation for Science and Technology ( FCT ) for Ph.D. ( SFRH / BD /147301/2019) and CEECIND/02919/2018 grants, respectively. Funding Information: This research was financially supported by: (i) Project POCI-01-0145-FEDER-031297 (CytoStraTech)—funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI) and by national funds (PIDDAC) through FCT /MCTES; (ii) NORTE-01-0145-FEDER-000069 (Healthy Waters) co-funded by European Regional Development Fund ( ERDF ), through North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement; (iii) UIDB/04750/2020 (EPIUnit) and LA/P/0064/2020 (ITR), funded by national funds through the FCT - Foundation for Science and Technology, I.P.; (iv) LA/P/0045/2020 (ALiCE), Base Fundings UIDB/00511/2020 and UIDP/00511/2020 (LEPABE) and UIDB/50020/2020 and UIDP/50020/2020 (LSRE- LCM ), funded by national funds through FCT / MCTES (PIDDAC). Publisher Copyright: © 2023 The AuthorsAntineoplastic drugs are pharmaceuticals that have been raising concerns among the scientific community due to: (i) their increasing prescription in the fight against the disease of the twentieth century (cancer); (ii) their recalcitrance to conventional wastewater treatments; (iii) their poor environmental biodegradability; and (iv) their potential risk to any eukaryotic organism. This emerges the urgency in finding solutions to mitigate the entrance and accumulation of these hazardous chemicals in the environment. Advanced oxidation processes (AOPs) have been taken into consideration to improve the degradation of antineoplastic drugs in wastewater treatment plants (WWTPs), but the formation of by-products that are more toxic or exhibit a different toxicity profile than the parent drug is frequently reported. This work evaluates the performance of a nanofiltration pilot unit, equipped with a Desal 5DK membrane, in the treatment of real WWTP effluents contaminated (without spiking) with eleven pharmaceuticals, five of which were never studied before. Average removals of 68 ± 23% were achieved for the eleven compounds, with decreasing risks from feed to permeate for aquatic organisms from receiving waterbodies (with the exception of cyclophosphamide, for which a high risk was estimated in the permeate). Aditionally, no significative impact on the growth and germination of three different seeds (Lepidium sativum, Sinapis alba, and Sorghum saccharatum) were determined for permeate matrix in comparison to the control.publishersversionpublishe

    Fullerenes In Asphaltenes And Other Carbonaceous Materials: Natural Constituents Or Laser Artifacts.

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    The presence of fullerenes as natural constituents of carbonaceous materials or their formation as laser artifacts during laser desorption ionization (LDI) mass spectrometry (MS) analysis is reinvestigated and reviewed. The results using asphaltene samples with varying composition as well as standard polycyclic aromatic hydrocarbons (PAH) and fullerene samples as models have demonstrated that indeed Cn ring fullerenes are not natural constituents but they are formed as common and often as predominant artifacts upon laser radiation, and a series of incorrect assignments based on LDI-MS data of several carbonaceous materials seems unfortunately to have been made. When the present results are evaluated also in the light of the vast literature on LDI-MS of carbonaceous materials, the formation of fullerene artifacts seems particularly common for LDI-MS analysis of asphaltenes and other carbonaceous samples with considerably high levels of PAH and varies according to the type of laser used, and the intensity of the laser beam.14

    Chemical Composition and Fermentation Profile of Perennial Peanut and Marandu Grass Mixed Silages

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    Perennial peanut has high quality, evidenced by the improvement of animal production in grazing, due to good contents of crude protein and digestibility, which makes it one of the best alternatives for low cost feeding (Paganella and Valls 2002). Grass ensilage associated with legumes is considered an alternative to meet the protein demand of cattle in the livestock. However, due to limited information on the techniques of grass ensilage with tropical legumes, this research aimed to evaluate the chemical composition and the fermentation profile of perennial peanut and Marandu mixed grass silages, treated or not with bacterial inoculant

    Methicillin-resistant Staphylococcus epidermidis carrying biofilm formation genes: detection of clinical isolates by multiplex PCR

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    Staphylococcus epidermidis is the most prevalent coagulase-negative Staphylococcus (CNS) and is a major cause of hospital bacteremia. Based on 18 reference strains and 149 Staphylococcus clinical strains, used in a novel multiplex PCR method, the aim of this study was to identify S. epidermidis with respect to the sequence of three genes: recN, which encodes a recombination/repair protein, mecA (methicillin resistance), and icaAB, which is involved in biofilm formation. Amplicons of 219 bp (S. epidermidis-recN gene), 154 bp (mecA gene), and 546 bp (icaAB genes) were obtained. Reliableresults were achieved for 100% of the evaluated strains, suggesting that this new multiplex-PCR approach could be useful forthe accurate identification of methicillin-resistant S. epidermidis with the potential to produce biofilm. [Int Microbiol 2011;14(1):13-17

    Association between body composition, balance and mobility of elderly aged 80 years or older

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    Modelo do estudo: Estudo transversal. Objetivo: O objetivo do presente estudo foi analisar a associação entre composição corporal, mobilidade e equilíbrio de idosos com idade igual ou superior a 80 anos. Métodos: A amostra foi composta por 123 idosos com idade entre 80 e 95 anos (83,2±2,7 anos), sendo 78 mulheres (83,2±2,9 anos) e 45 homens (83,2±2,4 anos) residentes na área urbana de Presidente Prudente - SP. A avaliação da composição corporal foi feita pelo método de Absorciometria por Dupla Emissão de Raios-X (DEXA). A mobilidade e o equilíbrio foram avaliados por meio dos testes de velocidade para caminhar, equilíbrio estático e força de membros inferiores. Para tratamento estatístico realizou-se o teste qui-quadrado, o software utilizado foi SPSS (13.0) e o nível de significância estabelecido foi de 5%. Resultados: No grupo masculino, os idosos com maior desempenho nos testes funcionais apresentaram maiores valores percentuais de massa muscular (MM) (35,6%) comparados aos de menor desempenho (15,6%), p=0,026. No grupo feminino, as idosas com maior desempenho nos testes apresentaram maiores valores de densidade mineral óssea (DMO) (30,8%) comparadas as de menor desempenho (20,5%) p=0,041. Conclusão: A MM para idosos do sexo masculino e a DMO para o sexo feminino foram os componentes da composição corporal que se associaram com a capacidade funcional.Study design: cross-sectional study. Objective: The objective of this study was to analyze the association between body composition, mobility and balance of elderly aged 80 years or older. Methods: The sample consisted of 123 elderly aged 80 and 95 years (83.2 ± 2.7 years) with 78 women (83.2 ± 2.9 years) and 45 men (83.2 ± 2, 4 years) residing in the city of Presidente Prudente - SP. Assessment of body composition was made by absorpiometria dual energy X-ray (DXA). The mobility and balance were assessed by means of tests of speed walking, and static balance lower limb strength. For statistical analysis we carried out the chi-square test, the software used was SPSS (13.0) and the significance level was set at 5%. Results: In males, those with higher performance in the functional tests showed higher percentages of muscle mass (MM) (35.6%) compared to lower performance (15.6%), p = 0.026. In the female group,the elderly with higher performance on tests showed higher bone mineral density (BMD) values (30.8%)compared with those with lower performance (20.5%) p = 0.041. Conclusion: MM for elderly males and BMD for females were the components of body composition that is associated with functional capacity
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