The glycatome

Funding Information: This study was supported by iNOVA4Health UID/Multi/04462/2013 – UIDB/04462/2020 and UIDP/04462/2020 , a program financially supported by Fundação para a Ciência e a Tecnologia (FCT) / Ministério da Ciência, Tecnologia e Ensino Superior, through national funds; and by Sociedade Portuguesa de Diabetologia . AC was supported by PD/BD/136863/2018 , FCT.We are witnessing a considerable increase in the incidence of Parkinson's disease (PD), which may be due to the general ageing of the population. While there is a plethora of therapeutic strategies for this disease, they still fail to arrest disease progression as they do not target and prevent the neurodegenerative process. The identification of disease-causing mutations allowed researchers to better dissect the underlying causes of this disease, highlighting, for example, the pathogenic role of alpha-synuclein. However, most PD cases are sporadic, which is making it hard to unveil the major causative mechanisms of this disease. In the recent years, epidemiological evidence suggest that type-2 diabetes mellitus (T2DM) individuals have higher risk and worst outcomes of PD, allowing to raise the hypothesis that some dysregulated processes in T2DM may contribute or even trigger the neurodegenerative process in PD. One major consequence of T2DM is the unprogrammed reaction between sugars, increased in T2DM, and proteins, a reaction named glycation. Pre-clinical reports show that alpha-synuclein is a target of glycation, and glycation potentiates its pathogenicity which contributes for the neurodegenerative process. Moreover, it triggers, anticipates, or aggravates several PD-like motor and non-motor complications. A given profile of proteins are differently glycated in diseased conditions, altering the brain proteome and leading to brain dysfunction and neurodegeneration. Herein we coin the term Glycatome as the profile of glycated proteins. In this review we report on the mechanisms underlying the association between T2DM and PD, with particular focus on the impact of protein glycation.publishersversionpublishe

Protocolo Híbrido de Ordem Total Uniforme com entrega Optimista

Broadcast algorithms with total uniform order simplify the development of applications that use replication as a fault-tolerance technique. This paper presents and compares three alternatives to implement an optimistic delivery service in total order uniform broadcast protocols for large-scale systems

Trick or Treat?

Funding Information: Funding: AC and FOM were supported by grants and contracts from the Portuguese Foundation for Science and Technology, PD/BD/136863/2018 and CEECIND/04266/2017, respectively.Accumulating evidence suggests the existence of a strong link between metabolic syndrome and neurodegeneration. Indeed, epidemiologic studies have described solid associations between metabolic syndrome and neurodegeneration, whereas animal models contributed for the clarification of the mechanistic underlying the complex relationships between these conditions, having the development of an insulin resistance state a pivotal role in this relationship. Herein, we review in a concise manner the association between metabolic syndrome and neurodegeneration. We start by providing concepts regarding the role of insulin and insulin signaling pathways as well as the pathophysiological mechanisms that are in the genesis of metabolic diseases. Then, we focus on the role of insulin in the brain, with special attention to its function in the regulation of brain glucose metabolism, feeding, and cognition. Moreover, we extensively report on the association between neurodegeneration and metabolic diseases, with a particular emphasis on the evidence observed in animal models of dysmetabolism induced by hypercaloric diets. We also debate on strategies to prevent and/or delay neurodegeneration through the normalization of whole-body glucose homeostasis, particularly via the modulation of the carotid bodies, organs known to be key in connecting the periphery with the brain.publishersversionpublishe

Numerical study of micromixing combining alternate flow and obstacles

Mixing in microsystems, combining alternate flow with obstacles, is studied by numerical methods. Simulations show that the layers of high and low solute concentrations, created by the alternate flow, are split into smaller chunks of fluid by obstacles inserted in the mixing channel, decreasing the critical mixing length. Reverse flow is necessary to guarantee symmetry and good mixing. Mixing increases with the increase of the number of obstacles. Increase of frequency improves mixing but requires an increase of reverse flow. The improvement in the mixing process shows that this method is very useful for designing mixers for lab-on-a-chip devices.Support for this research was provided by the Engineering School of University of Minho (program IN2TEC) and the Portuguese Science Foundation (grant FTDC/B10/70017/2006 and grant SFRH/BPD/17689/2004)

Oscillatory and alternate flows in a microfluidic device

The mixing properties of systems with oscillatory or alternate flows are studied by numerical methods. Preliminary results show that, for alternate flows, the contact area between high and low concentration regions increases and mixing is achieved from the combination of transversal diffusion and axial advection. The improvement in the mixing process shows that this method is very useful for designing mixers in lab-on-a-chip devices.R&D Centre Algoritmi - University of Minho Engineering School (program IN2TEC) - University of Minho

Configuração do Suporte de Comunicação em Ambientes Multi-Utilizador Orientados aos Objectos

Os sistemas distribuídos interactivos multi-utilizador são aplicações que colocam um complexo conjunto de requisitos sobre o suporte de comunicação subjacente. Um modo de satisfazer cabalmente estes requisitos consiste em utilizar arquitecturas de comunicação configuráveis que suportam a reutilização e composição de componentes. O projecto MOOSCo, "Multi-user Object-Oriented environments with Separation of Concerns" aborda o problema da configuração em sistemas interactivos multi-utilizador. Para suportar a comunicação entre as entidades distribuídas, o projecto recorre ao Appia, uma plataforma de composição de protocolos configurável, que fornece a comunicação em grupo. Este artigo discute o papel do Appia na arquitectura MOOSCo e pretende mostrar como é possível, de uma forma simples e elegante, obter a composição de protocolos mais adequada dependendo dos objectos partilhados pelo ambiente multi-utilizado

Biological Properties of Solid Free Form Designed Ceramic Scaffolds with BMP-2: In Vitro and In Vivo Evaluation

Porous ceramic scaffolds are widely studied in the tissue engineering field due to their potential in medical applications as bone substitutes or as bone-filling materials. Solid free form (SFF) fabrication methods allow fabrication of ceramic scaffolds with fully controlled pore architecture, which opens new perspectives in bone tissue regeneration materials. However, little experimentation has been performed about real biological properties and possible applications of SFF designed 3D ceramic scaffolds. Thus, here the biological properties of a specific SFF scaffold are evaluated first, both in vitro and in vivo, and later scaffolds are also implanted in pig maxillary defect, which is a model for a possible application in maxillofacial surgery. In vitro results show good biocompatibility of the scaffolds, promoting cell ingrowth. In vivo results indicate that material on its own conducts surrounding tissue and allow cell ingrowth, thanks to the designed pore size. Additional osteoinductive properties were obtained with BMP-2, which was loaded on scaffolds, and optimal bone formation was observed in pig implantation model. Collectively, data show that SFF scaffolds have real application possibilities for bone tissue engineering purposes, with the main advantage of being fully customizable 3D structures

Survey of churches damaged by the 2012 Emilia-Romagna earthquake sequence

This report presents an overview of the damage that was observed in fourteen churches that were hit by the May 2012Emilia-Romagna earthquake sequence. The data was collected over the course of a two-day reconnaissance mission thattook place on the 9th and 10th of July 2012, and that involved researchers from the Civil engineering Department of theFaculty of Engineering of the University of Porto and of the University of Aveiro, both institutions from Portugal.It is noted that the current report only focusses the post-seismic damage assessment of churches and does not address thecultural and artistic losses associated to movable or immovable heritage. Furthermore, it is also referred that since thereconnaissance mission took place after the major earthquakes of the 20th and the 29th of May, the source of the reporteddamages is not assigned to a particular event and must be seen as the cumulative effect of several ground motions

What is the real impact of on-site percutaneous coronary intervention? A propensity score analysis of patients admitted with acute coronary syndrome

© 2020 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. Este é um artigo Open Access sob uma licença CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).Introduction: In an era in which coronary heart disease is one of the leading causes of death worldwide, several studies report the persistence of obstacles to accessing revascularization, and percutaneous coronary intervention in particular, which may be associated with worse outcomes. Objectives: To compare cardiovascular outcomes in patients admitted to hospitals with and without on-site percutaneous coronary intervention (PCI) capabilities. Material and methods: A retrospective study based on the National Registry of Acute Coronary Syndromes (ACS) - with data collection from 2010 to 2018. Division of the patients into two groups: with and without ST-elevation. Two subgroups were subsequently created according to the presence/absence of on-site PCI. A propensity score was performed to standardize the results. Patients without information about hospital admission (with/without PCI) were excluded. Results: 6008 patients were included after exclusion criteria and propensity score were applied. We found that patients admitted for ACS with ST-elevation (STE-ACS) had more episodes of sustained ventricular tachycardia (OR 2.14; CI (1.26-3.61); p=0.004) in hospitals without on-site PCI. Regarding ACS without ST elevation (NSTE-ACS), there were more cases of congestive heart failure (OR 0.79; CI (0.65-0.98)) in hospitals with on-site PCI. Conclusion: The incidence of a greater number of major adverse events in hospitalizations without on-site PCI, particularly in the case of STE-ACS, is a consequence of the delay before revascularization. National and local strategies must be established to reduce the negative impact of the absence of on-site PCI and the resulting time before revascularization.Introdução: Numa era em que a doença coronária é uma das principais causas de morte a nível mundial, vários estudos referem a persistência de obstáculos no acesso à revascularização, sobretudo na facilidade de acesso à intervenção coronária percutânea, podendo tal estar asso- ciado a piores outcomes. Objetivos: Comparar os outcomes cardiovasculares dos doentes submetidos a intervenção coronária percutânea (ICP) em hospitais com e sem intervenção on-site. Material e métodos: Estudo retrospetivo baseado no Registo Nacional de Síndromes Coronárias Agudas (SCA) --- com colheita de dados de 2010 a 2018. Divisão dos SCA em dois grupos: com e sem supradesnivelamento do segmento ST. Criados ainda dois subgrupos, de acordo com a presenc ̧a/ausência de ICP on-site, para cada uma destas entidades. Realizado score de pro- pensão (SdP) para uniformização dos resultados. Excluídos doentes sem informação sobre a realização de ICP. Resultados: Admitidos 6008 doentes após aplicação de critérios de exclusão e SdP. Verificamos que os doentes admitidos por SCA com supraST apresentaram mais episódios de taquicardia ventricular mantida (OR 2,14; IC (1,26-3,61); p = 0,004) em hospitais sem ICP on-site. Relativamente aos SCA sem supraST, verificou-se um predomínio de insuficiência cardíaca congestiva (ICC) (OR 0,79; IC (0,65-0,98); p = 0,03) em hospitais com ICP on-site. Conclusão: A ocorrência de um maior número de eventos adversos major nos hospitais sem ICP on-site, em particular no caso do SCA com supraST, é consequência do atraso até a revascularização. Estratégias nacionais e locais devem ser definidas para reduzir o impacto negativo da ausência de ICP on-site e consequente tempo até revascularização.info:eu-repo/semantics/publishedVersio

The Neuroprotective Action of Amidated-Kyotorphin on Amyloid β Peptide-Induced Alzheimer’s Disease Pathophysiology

Kyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous dipeptide initially described to have analgesic properties. Recently, KTP was suggested to be an endogenous neuroprotective agent, namely for Alzheimer’s disease (AD). In fact, KTP levels were shown to be decreased in the cerebrospinal fluid of patients with AD, and recent data showed that intracerebroventricular (i.c.v.) injection of KTP ameliorates memory impairments in a sporadic rat model of AD. However, this administration route is far from being a suitable therapeutic strategy. Here, we evaluated if the blood-brain permeant KTP-derivative, KTP-NH2, when systemically administered, would be effective in preventing memory deficits in a sporadic AD animal model and if so, which would be the synaptic correlates of that action. The sporadic AD model was induced in male Wistar rats through i.c.v. injection of amyloid β peptide (Aβ). Animals were treated for 20 days with KTP-NH2 (32.3 mg/kg, intraperitoneally (i.p.), starting at day 3 after Aβ administration) before memory testing (Novel object recognition (NOR) and Y-maze (YM) tests). Animals were then sacrificed, and markers for gliosis were assessed by immunohistochemistry and Western blot analysis. Synaptic correlates were assessed by evaluating theta-burst induced long term potentiation (LTP) of field excitatory synaptic potentials (fEPSPs) recorded from hippocampal slices and cortical spine density analysis. In the absence of KTP-NH2 treatment, Aβ-injected rats had clear memory deficits, as assessed through NOR or YM tests. Importantly, these memory deficits were absent in Aβ-injected rats that had been treated with KTP-NH2, which scored in memory tests as control (sham i.c.v. injected) rats. No signs of gliosis could be detected at the end of the treatment in any group of animals. LTP magnitude was significantly impaired in hippocampal slices that had been incubated with Aβ oligomers (200 nM) in the absence of KTP-NH2. Co-incubation with KTP-NH2 (50 nM) rescued LTP toward control values. Similarly, Aβ caused a significant decrease in spine density in cortical neuronal cultures, and this was prevented by co-incubation with KTP-NH2 (50 nM). In conclusion, the present data demonstrate that i.p. KTP-NH2 treatment counteracts Aβ-induced memory impairments in an AD sporadic model, possibly through the rescuing of synaptic plasticity mechanisms.publishersversionpublishe