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Os impactos da perda de biodiversidade no funcionamento de ecossistemas ribeirinhos quando sujeitos a agentes de stress relacionados com as alterações climáticas
No full textTese de doutoramento em Molecular and Environmental Biology (especialização em Evolution, Biodiversity and Ecology)O Antropoceno tem sido o principal catalisador das alterações globais. Os ecossistemas de água doce são um recurso vital que apoia a subsistência humana. Estes ecossistemas são muito suscetíveis aos impactos de múltiplos agentes de stress relacionados com as alterações globais. Antecipar os efeitos das alterações globais nos ecossistemas de água doce é fundamental para garantir a sustentabilidade dos bens e serviços providenciados por estes ecossistemas. Além disso, nestes ecossistemas, as espécies estão a desaparecer a taxas alarmantes, representando ameaças significativas ao funcionamento destes sistemas. Em ribeiros de baixa ordem, os fungos aquáticos são os principais intervenientes microbianos na decomposição da matéria orgânica proveniente da vegetação ribeirinha, processo que permite o acesso do carbono, dos nutrientes e da energia a outros níveis tróficos. Não se sabe se a diversidade de fungos aquáticos também está a ser perdida a taxas alarmantes, mas é importante reconhecer e quantificar os processos ecológicos assegurados por estes microrganismos. O principal objetivo da investigação realizada nesta tese foi avaliar os impactos de agentes de stress múltiplos relacionados com as alterações globais, nomeadamente aumento da temperatura e dos nutrientes e ocorrência de seca, no funcionamento dos ecossistemas ribeirinhos, particularmente, nos fungos decompositores e no processo de decomposição. A investigação revelou que a decomposição foi estimulada pelo aumento da temperatura e dos nutrientes, mas inibida pela seca. Observaram-se efeitos interativos entre os agentes de stress múltiplos. Os impactos do aumento da temperatura, do aumento de nutrientes e da seca foram modulados pela identidade dos fungos, em comunidades de fungos construídas no laboratório, e pela riqueza taxonómica de fungos, em comunidades fúngicas naturais. Os efeitos da biodiversidade foram geralmente positivos, mesmo sob a pressão de agentes de stress, e a presença de algumas espécies ajudou na recuperação de outras. Os resultados mostram ainda, que a importância da diversidade intraespecífica aumenta em condições de stress, o que é relevante para a manutenção de espécies no atual contexto de alterações globais. As nossas observações têm implicações para a conservação dos ecossistemas de água doce e enfatizam a adoção de abordagens holísticas que considerem a diversidade dos fungos na gestão e conservação eficaz destes ecossistemas.The Anthropocene is considered the primary catalyst for global change. Freshwaters are a vital resource that support human livelihoods. These ecosystems are highly susceptible to the impacts of multiple stressors related to global change. Anticipating the effects of global change on biodiversity and the functioning of freshwater ecosystems is crucial for securing the sustainability of water resources. Within freshwater ecosystems, species are vanishing at alarming rates, posing significant threats to the functioning of these systems. In low-order streams, aquatic fungi are the main microbial players in the decomposition of organic matter from riparian vegetation, a process that allows the access of carbon, nutrients and energy to higher trophic levels. It is unknown whether aquatic fungal diversity is being lost, but recognizing and quantifying the value of ecosystem processes driven by these microorganisms is of utmost importance. The main objective of the research conducted in this thesis was unraveling the impacts of multiple stressors related to global change, namely increasing temperature, increasing nutrients, and drying, on the functioning of freshwater ecosystems, particularly, on fungal decomposers and decomposition. Results revealed that decomposition was stimulated by increased temperature and nutrients but inhibited by drying. Interactive effects between multiple stressors were observed. The impacts of all stressors were modulated by fungal identity, when evaluating constructed fungal assemblages and by fungal richness, when evaluating natural fungal communities. Also, the effects of fungal biodiversity were mainly positive, even under the pressure of multiple stressors, and the presence of some species assisted in the recovery of others. Finally, results showed that intraspecific diversity became more important under stress and may contribute to species maintenance under the ongoing global change. Our observations hold important implications for freshwater conservation and emphasize the adoption of holistic approaches considering fungal diversity as crucial for effective freshwater ecosystem management and conservation.I would like to express my gratitude to the funding agencies and institutions that have supported
my research work, namely Fundação para a Ciência e Tecnologia (FCT) (SFRH/BD/140761/2018). I
also thank the STREAMECO “Biodiversity and ecosystem functioning under climate change: from the
gene to the stream” project (PTDC/CTA-AMB/31245/2017), funded by the Portuguese Foundation for
Science and Technology (FCT) and the “Contrato-Programa” (UIDB/04050/2020) funded by national
funds through the FCT I.P. (https://doi.org/10.54499/UIDB/04050/2020). Finally, I would like to thank
the Aquatic Research Infrastructure Network (ARTNET, https://doi.org/10.54499/LA/P/0069/2020)
Polycaprolactone/sodium alginate coaxial wetspun fibers modified with carbon nanofibers and ceftazidime for improved clotting and infection control in wounds
No full textChronic wounds (CWs) are a significant public health concern and affect 1–2% of the world’s population. They are responsible for high morbidity and mortality rates. Bacterial infections caused by Staphylococcus aureus and Pseudomonas aeruginosa are very common in CWs and prevent normal wound healing steps from taking place. Carbon nanofibers (CNFs) have attracted interest due to their inherent antibacterial and blood clotting abilities, as well as mechanical strength. The aim of this research was to engineer coaxial fibers by wet-spinning as new platforms for drug delivery in CW care (promoting rapid blood clotting and consequent tissue regeneration). Coaxial fibers were produced with an outer layer (shell) made of a mechanically resilient polycaprolactone (PCL at 10 wt%) reinforced with carbon nanofibers (CNFs at 50, 100, and 150 μg mL−1 ), while the inner layer (core) was made of a highly hydrated mixture of 2 wt% sodium alginate (SA) loaded with ceftazidime (CZ) at 128 μg mL−1 (minimum bactericidal concentration). The fibers’ double-layer structure was verified by scanning electron microscopy. Core–shell fibers were deemed highly flexible and mechanically resilient and resistant to rupture, with such properties being improved with the incorporation of CNFs. Most fibers preserved their structural integrity after 28 days of incubation in physiological-like medium. Furthermore, data reported the ability of CZ combined with CNFs to fight microbial proliferation and showed that the presence of CNFs promoted blood clotting, with PCL/CNFs50 being the most effective from the group. It was found that higher concentrations of CNFs had a detrimental effect, highlighting a concentration-dependent response. The presence of PLC in the fibers resulted in a mitigation of the CNFs’ cytotoxic impact on keratinocytes. The incorporation of CZ had no effect on the metabolic activity of the cells. Overall, the results demonstrated the potentialities of the engineered coaxial fibers for applications in wound care.This work was funded by the European Regional Development Fund through the Operational Competitiveness Program and the National Foundation for Science and Technology of Portugal (FCT) under the projects UID/CTM/00264/2020 of the Centre for Textile Science and Technology (2C2T) on its components Base (https://doi.org/10.54499/UIDB/00264/2020) and programmatic (https://doi.org/10.54499/UIDP/00264/ 2020). C. S. M. acknowledges FCT for PhD funding via scholarship 2020.08547.BD. H. P. F. also acknowledges FCT for auxiliary researcher contract 2021.02720.CEEIND
Production of affinity columns for Mycotoxins with protein aerogels
No full textDissertação de mestrado em Engenharia Química e BiológicaAs micotoxinas são metabolitos secundários tóxicos produzidos por certos fungos
filamentosos, presentes em vários tipos de alimentos. Estes representam uma ameaça para a
saúde humana e animal, visto que são responsáveis por induzir efeitos de toxicidade crónica
graves na saúde. Os métodos frequentemente utilizados para a sua deteção baseiam-se em
técnicas cromatográficas de afinidade. Devido ao seu alto custo e baixa reutilização, existe a
necessidade de desenvolver novas abordagens para a separação e pré-concentração de
micotoxinas.
Desta forma, este estudo propõe um novo método de separação de micotoxinas,
baseado na utilização de colunas de afinidade à base de proteínas, nomeadamente a albumina
do soro bovino (BSA) e a ovalbumina (OVA). Estas foram estruturadas na forma de aerogéis, dado
que este tipo de material tem despertado grande interesse em várias aplicações, devido às suas
inúmeras vantagens como elevada porosidade e resistência mecânica. Assim, foi realizada uma
otimização das melhores condições de produção de aerogéis de BSA e OVA, a partir de um
desenho experimental Box–Behnken. No caso da BSA, também se estudou a diferença entre os
métodos de indução de gelificação a quente e a frio. Posteriormente, avaliaram-se os aerogéis
com melhores propriedades físicas na captura de ocratoxina A (OTA), tanto em solução-tampão
como em matriz de cerveja.
As colunas de afinidade com aerogéis de OVA e BSA, tanto induzidas por gelificação a
quente como a frio, mostraram-se capazes de capturar eficazmente a micotoxina. Em particular,
a coluna de BSA preparada por gelificação a quente com as condições ótimas do desenho
experimental (nº V1a), apresentou boa repetibilidade e manteve-se estruturalmente estável
durante 8 ensaios de afinidade (5 ensaios de OTA em solução-tampão e 3 ensaios com matriz de
cerveja). Além disso, as taxas de recuperação de OTA variaram de 60 % a 107 % utilizando 3 mL
de metanol acidificado com 2 % de ácido acético. Desta forma, as colunas de afinidade
mostraram ter potencial para serem utilizadas na separação de OTA em matrizes alimentares,
como observado com a cerveja. Por outro lado, será necessário realizar mais otimizações na
etapa de eluição de forma a validar o seu uso como técnica analítica.Mycotoxins are toxic secondary metabolites produced by certain filamentous fungi that
are present in various types of food. They represent a threat to human and animal health, as
they are responsible for inducing serious chronic toxicity effects on health. The methods often
used to detect them are based on affinity chromatographic techniques. Due to their high cost
and low reusability, there is a need to develop new approaches for the separation and
preconcentration of mycotoxins.
This study proposes a new method for separating mycotoxins, based on the use of
protein-based affinity columns, namely bovine serum albumin (BSA) and ovalbumin (OVA).
These were structured in the form of aerogels, as this type of material has aroused great interest
in various applications due to its numerous advantages such as high porosity and mechanical
resistance. The best production conditions for BSA and OVA aerogels were optimized using a
Box-Behnken experimental design. In the case of BSA, the difference between hot and cold
gelation induction methods was also studied. Subsequently, the aerogels with the best physical
properties for capturing ochratoxin A (OTA) were evaluated, both in buffer solution and in beer
matrix.
The affinity columns with OVA and BSA aerogels, induced by both hot and cold gelation,
were capable of effectively capturing the mycotoxin. In particular, the BSA column prepared by
hot gelation with the optimal conditions of the experimental design (nº V1a), showed good
repeatability and remained structurally stable during 8 affinity tests (5 tests for OTA in buffer
solution and 3 tests with beer matrix). In addition, OTA recovery rates ranged from 60 % to 107
% using 3 mL of methanol acidified with 2 % acetic acid. In this way, the affinity columns showed
potential to be used as a separation method for OTA in food matrices, as observed with beer.
On the other hand, it will be necessary to carry out further optimizations in the elution stage to
validate its use as an analytical technique.Por fim, gostaria de agradecer o apoio da Fundação para a Ciência e Tecnologia (FCT) e
ao projeto MycoProAffinity (https://doi.org/10.54499/2022.03438.PTDC) pela bolsa de
investigação UMINHO/BIM/2023/91
A point-of-care device for Sepsis Diagnosis
No full textDissertação de mestrado em Biomedical Engineering on Medical ElectronicsSepsis is a life-threatening condition characterized by a dysregulated host response to infection, often leading to severe complications such as septic shock and multiple organ dysfunction syndrome (MODS). Rapid diagnosis is crucial, as delays in antibiotics administration significantly increase the risk of mortality. Blood cultures (BC) are currently the gold standard for infection diagnosis although they are time-consuming, taking up to 72 hours and are prone to false negatives. Successful sepsis management depends on the prompt and accurate identification of the infecting pathogen, allowing for the timely administration of targeted antibiotic therapy.
In response to this clinical challenge, this thesis introduces a novel electrochemical sensor for the rapid detection of bacterial infections associated with sepsis, particularly those caused by Klebsiella pneumoniae, a pathogen known to be one of the most prevalent bacteria in sepsis cases. This innovative strategy integrates magnetic nanoparticles (MNPs) functionalized with bacterio(phage) receptor binding proteins (RBPs), enabling precise targeting and efficient capture of target bacterial cells. By integrating these features, the biosensor takes advantage of the combined benefits of electrochemical sensors – high sensitivity, rapid response times and suitability for point-of-care (POC) applications – while also leveraging the unique advantages of RBPs, which provide specificity to bacterial species, stability in solution and ease of conjugation with labelling elements. Furthermore, MNPs enhance the biosensor’s capabilities by enabling precise targeting and efficient capture of bacteria, while facilitating the removal of interfering blood components, thereby optimizing sensor performance even in complex matrices such as whole blood. The developed biosensor was tested in buffer and whole blood spiked with the target (K. pneumoniae) and non-target pathogen (Escherichia coli), demonstrating specific detection with a dynamic quantitative range from around 101 to 104 colony-forming units per millilitre (CFU/mL). This performance is clinically relevant, as bacterial concentrations in septic patients typically range from 1-100 (CFU/mL) [1].
Therefore, this work elucidates the potential of the developed electrochemical sensor for the POC diagnosis of sepsis-related bacterial infections, positioning it as a groundbreaking tool against sepsis.A sépsis é uma condição potencialmente fatal, caracterizada por uma resposta desregulada do hospedeiro à infeção, que frequentemente resulta em complicações graves, como o choque séptico e a síndrome de disfunção multiorgânica (SDMO). O diagnóstico rápido é crucial, pois os atrasos na administração de antibióticos aumentam significativamente o risco de mortalidade. Atualmente, as hemoculturas são os métodos de referência para o diagnóstico de infeções, embora sejam demoradas, podendo levar até 72 horas a fornecer resultados, e estão sujeitas a falsos negativos. A gestão eficaz da sépsis depende da identificação rápida e precisa do agente infecioso, permitindo a administração de terapias antibióticas atempadamente.
Em resposta a este desafio clínico, esta tese introduz um sensor eletroquímico inovador para a deteção rápida de infeções bacterianas associadas à sépsis, particularmente as causadas por Klebsiella pneumoniae, um dos patógenos mais prevalentes em casos de sépsis. Esta estratégia inovadora integra nanopartículas magnéticas (NPMs) funcionalizadas com proteínas de bacterió(fagos) (fágicas) de ligação a recetores (PLRs), permitindo a identificação precisa e a captura eficiente das células bacterianas-alvo. Ao integrar estas características, o biossensor tira partido das vantagens combinadas dos sensores eletroquímicos — alta sensibilidade, tempos de resposta rápidos e adaptabilidade em point-of-care (POC) — ao mesmo tempo que explora as vantagens únicas das PLRs, que oferecem especificidade para espécies bacterianas, estabilidade em solução e facilidade de conjugação com agentes de marcação. Além disso, a inclusão de NPMs melhora as capacidades do biossensor ao permitir a captura precisa das bactérias e a remoção de componentes interferentes do sangue, otimizando assim o desempenho do sensor em matrizes complexas, como o sangue. O biossensor desenvolvido foi testado em solução tampão e em sangue inoculado com o patógeno-alvo (K. pneumoniae) e um patógeno não-alvo (Escherichia coli), demonstrando deteção específica com um intervalo quantitativo dinâmico de aproximadamente 10¹ a 10⁴ unidade formadoras de colónias por mililitro (UFC/mL). Este desempenho é clinicamente relevante, uma vez que as concentrações bacterianas em pacientes sépticos geralmente variam entre 1-100 UFC/mL [1].
Este trabalho destaca o potencial do sensor eletroquímico desenvolvido para o diagnóstico de infeções bacterianas relacionadas com a sépsis, posicionam-no como uma ferramenta inovadora no combate à sépsis
On the dependence of a minimum autoregressive exponential-type process
No full textGlobalization has led to the growth of interrelations in the most varied contexts. The risk inherent in an increase in dependence between the different variables is now a concern of analysts and researchers. The dependence at the tail level is a very useful tool in the evaluation of risk and can be analyzed in the scope of the theory of extreme values. In this work, we consider an autoregressive model of minima with several applications already explored in the literature and contribute to the characterization of its extreme correlation structure
Territorial cohesion: discussing the mismatch between conceptual definitions and the understanding of local and intra-regional public decision-makers
No full textThe European Union’s Cohesion Policy aims at strengthening economic, social and territorial cohesion to correct imbalances between countries and regions. However, European Union policy was expressed
unevenly, and asymmetries grew at different scales. Therefore, it has raised discussions on territorial cohesion, which looks much different on the ground than in its theoretical design. This paper confronts
this conceptual rationale with the perceptions of political decision-makers of the Centro Region in Portugal. Findings point out that public decision-makers in this region understand territorial cohesion
more due to good public policies rather than a process itself, demonstrating evident deficits of joint
regional action and some overvaluation of local specific problems and competition. Conclusions underline that territorial cohesion’s political agenda and policy design remained too focused on
territorial asymmetries within the region. A lack of a strategic regional vision for territorial development
is translated into implementing differentiated projects, with no vertical and horizontal coordination, and
instead passively responding to European funding requirements. Nevertheless, policymakers commonly
accepted that territorial cohesion should be measured considering five main conceptual dimensions,
although not highlighting the need to identify and collect indicators to assess it.This research was developed under the support of the Research Program 'CENTER - Community-Led Territorial Innovation' (CENTRO-01-0145-FEDER-000002), funded by the Programa Operacional Regional do Centro (CENTRO 2020) through the ERDF and PT 2020. The funding source had no involvement in the development of the research or in the preparation of the article
Of the administrative sanctioning power: contribution to the consolidation of its general dogmatics
No full textTese de doutoramento em Ciências Jurídicas (especialidade em Ciências Jurídicas Públicas)A presente investigação, centrada no campo da Ciência Jurídica Administrativa e com uma
abordagem eminentemente dogmático-substantiva e procedimental, debruça-se sobre o poder
administrativo sancionatório, especificamente sobre a questão da sua unidade conceptual, procurando
assim contribuir para a consolidação da sua teoria geral e, através dela, para a consolidação da própria
teoria geral do Direito Administrativo Sancionatório.
A investigação encontra-se dividida em duas Partes principais. Na Primeira Parte, procede-se à
compreensão da evolução histórica e comparatística do poder administrativo sancionatório, bem como
ao seu impulso internacionalista e cosmopolita. Pretende assim melhor apreender-se não só os
fundamentos da evolução e expansão do poder administrativo sancionatório, como também as suas
fontes históricas e a importância da normatividade supraestadual para a normatividade nacional neste
domínio. Na Segunda Parte, procura fixar-se o poder administrativo sancionatório como categoria jurídica
administrativa, avançando com a determinação do seu conceito e da sua natureza jurídica, aproximando-
-nos do seu extenso universo, perscrutando-lhe especificidade funcional e compreendendo o sentido e o
alcance de alguns dos seus princípios estruturantes, tendo em vista confirmar, simultaneamente, um
sentido maior de convergência que trespassa todas as suas modalidades ou formas de expressão e um
sentido particularizante ou diferenciador em relação a outros poderes sancionatórios públicos.
Trespassada por uma conceção axiológico-personalista do Direito, a investigação procura
igualmente sustentar que as situações de poder, como situações jurídicas conferentes de posições de
vantagem a determinados sujeitos, especificamente àqueles que exercem a função administrativa, não
se mostra contrária à ideia de Estado de Direito Democrático, antes se assume como pressuposto
essencial para a sua realização.The present research, focused on the field of Administrative Legal Science and with an
eminently dogmatic-substantive and procedural approach, focuses on the sanctioning administrative
power, specifically on the question of its conceptual unity, thus seeking to contribute to the consolidation
of its general theory and, through it, to the consolidation of the general theory of Administrative
Sanctioning Law itself.
The investigation is divided into two main parts. In the First Part, we proceed to the
understanding of the historical and comparative evolution of the sanctioning administrative power, as well
as its internationalist and cosmopolitan impulse. It is thus intended to better apprehend not only the
foundations of the evolution and expansion of the sanctioning administrative power, but also its historical
sources and the importance of suprastate normativity for national normativity in this field. In the Second
Part, it seeks to establish the sanctioning administrative power as an administrative legal category,
advancing with the determination of its concept and its legal nature, approaching its extensive universe,
scrutinizing its functional specificity and understanding the meaning and scope of some of its structuring
principles, with a view to confirming, at the same time, a greater sense of convergence that permeates
all its modalities or forms of expression and a particularizing or differentiating sense in relation to other
public sanctioning powers.
Pierced by an axiological-personalist conception of Law, the research also seeks to maintain
that situations of power, as legal situations conferring positions of advantage to certain subjects,
specifically those who exercise the administrative function, is not contrary to the idea of the Rule of Law,
but is assumed as an essential presupposition for its realization.Fundação para a Ciência e a Tecnologia (FCT) - bolsa de doutoramento SFRH/BD/145611/201
Da legitimação do Direito Processual Penal Militar à luz do direito angolano
No full textDissertação de mestrado em Direito Judiciário (Direitos Processuais e Organização Judiciária)A Legitimação do Direito Processual Penal Militar, à Luz do Direito Angolano. O processo penal militar em Angola tem uma estrutura e sujeitos próprios e específicos, não obstante o facto de a jurisdição penal servir de auxílio da jurisdição especializada, na medida em que a própria tramitação dos processos penais militares são muito mais céleres em relação ao comum sem desprimor das formalidades exigidas por lei com base no princípio da legalidade. A Justiça Militar em Angola pode ser vista em dois sentidos: uma que emergiu da luta pela independência do país, e que era praticada pelas forças de guerrilha que combatiam a ocupação colonial e que tinha características de uma justiça revolucionária; e outra que vigorava no território nacional sob ocupação colonial, coexistindo, assim, dois sistemas jurídicos totalmente diferentes e resultantes de duas realidades distintas. A autonomiado direito processual penal militar em relação ao direito penal e processual comum tem como fundamento a chamada “substantividade” desse ramo do direito, haja vista a existência de normativa penal e processual penal específica. Igualmente, ressaltam a existência de uma justiça “própria” para julgar os crimes ali previstos. A vasta dimensão do território nacional e consequentemente das Forças Armadas Angolanas, da Polícia Nacional e dos Órgãos de Segurança e de Ordem Interna como garantes da defesa do território bem como da ordem e tranquilidade pública justificam a razão de ser da jurisdição militar em Angola, razão pela qual o legislador constituinte, diferentemente de outros ordenamentos jurídicos, deu dignidade constitucional aos órgãos que intervêm na administração da justiça militar, enquanto jurisdição especializada. O ordenamento jurídico-penal militar angolano privilegiou a tipificação dos crimes essencialmente militares com vista à salvaguarda dos bens jurídicos que, mesmo não sendo exclusivamente militares, são fundamentais para as forças armadas.The Legitimation of the Military Criminal Procedural Law, in the Light of Angolan Law. The Military criminal procedure in Angola has its own and specific structure and subjects, even though the criminal jurisdiction serves as an aid to the specialized jurisdiction, insofar as the conduct of military criminal proceedings is much faster in relation to the common without disdain of the formalities required by the law based on the principle of legality. The Military Justice in Angola can be seen in two ways: one that emerged from the war for the country's independence, which was practiced by the insurgent forces that fought the colonial occupation and had characteristics of revolutionary justice; and the other that was in vigor in the national territory under colonial occupation; thus, coexisting two totally different legal systems resulting from two distinct realities. The autonomy of the military criminal and procedural law in relation to common criminal and procedural law is based on the so- called “substantivity” oh this branch of law, given the existence of criminal regulations and specific criminal procedural. Likewise, they emphasize the existence of their “own” justice to judge the crimes foreseen therein. The vast dimension of the national territory and consequently of the Angolan Armed Forces, the National Police and the Bodies of Security and Internal Order as guarantors of the defense of the territory as well as public order and tranquility, justify the reason for the existence of military jurisdiction in Angola. For that reason, the constituent legislator, unlike other legal systems, gave constitutional right to the bodies that intervene in the administration of military justice, as a specialized jurisdiction. The Angolan military legal-penal system favored the classification of crimes essentially military with the goal of safeguarding legal assets that, even if not exclusively military, are fundamental to the armed forces
As ações do stress crónico e dos glucocorticoides na plasticidade cerebral e na patologia da proteína Tau
No full textTrabalho de Doutoramento realizado em cotutela: Doutoramento em Envelhecimento e Doenças Crónicas
e École Doctorale Cerveau, Cognition, Comportement (Paris, no 158)Chronic stress and high levels of the stress hormone, glucocorticoid (GC), are implicated in susceptibility to brain pathologies such as depression or Alzheimer’s disease (AD), as they promote neural plasticity damage and glial reactivity, which can lead to dendritic/synaptic loss, reduced neurogenesis, mood deficits, and impaired cognition. Growing clinical evidence supports a pathological link between depression and AD and shared neurobiological underpinnings with chronic stress being a potential link between them. Exposure of AD animal models to chronic stress triggers Tau pathology (e.g. Tau hyperphosphorylation and accumulation); the latter is causally related to neuronal malfunction and atrophy. Despite the well-known role of Tau in regulating cytoskeletal dynamics, the involvement of Tau in neurostructural remodeling and neuroplastic damage caused by chronic stress in the adult brain remains poorly explored. In the first objective of my thesis, we demonstrated the crucial role of Tau and its malfunction in stress-driven neurogenic, but not astrogliogenic or oligodendrogenic, damage in the cytogenic niches of the adult brain of wild-type animals (hippocampus and subventricular zone-olfactory bulb system) as mice lacking Tau were protected against stress-driven neurogenic suppression. Also, we showed that chronic stress impacts differentially the distinct phases of maturation of newborn immature neurons in the adult hippocampus. The second objective of my thesis focused on the cell-specific actions of the glucocorticoid receptor, GR, in stress-induced Tau pathology. To examine the role of GR specifically in neurons or microglia under stress conditions, we generated P301LTau mice in which GR gene is conditionally inactivated either in forebrain neurons or in microglia. Our findings show that GR was required in both cell types for chronic stress to induce cognitive deficits. Further analyses (which are ongoing) showed that neuronal GR is important in precipitating Tau neuropathology, and apical spine loss in CA1 hippocampal area. Microglial GR was found to affect microglial reactivity both in response to P301LTau as well as chronic stress-induced Tau pathology. Deletion of microglial GR results in spine loss whereas, it promotes spinogenesis under stress. However, it does not appear to impact Tau aggregation/accumulation. In conclusion, our data point to an important role of neuronal GR in mediating stress-driven Tau neuropathology and also identifies the essential role of microglial GR in stress-induced cognitive deficits. Given that the modern lifestyle increasingly exposes individuals to high stress loads, it is clear that understanding the mechanistic link(s) between chronic stress and AD pathogenesis may facilitate the treatment of AD and other related disorders.O stress crónico e as hormonas do stress, glucocorticoides, são sugeridos como causadores de suscetibilidade neuronal, estando associados a danos na plasticidade cerebral (ex. perda dendrítica/sináptica, neurogénese reduzida), inflamação, bem como a distúrbios neurológicos, como depressão e a doença de Alzheimer (DA); onde o dano da neuroplasticidade é um processo muito importante. Evidências clínicas apoiam uma ligação patológica entre a depressão e a DA, e fundamentos neurobiológicos observados no stress crónico indicam que este pode ser um fator de ligação entre elas. A exposição de modelos animais da DA a stress crónico desencadeiam patologia da proteína Tau, que parece estar relacionada com atrofia e o mau funcionamento neuronal. Tendo como função a regulação do citoesqueleto, a proteína Tau tem um papel importante e inexplorado na remodelação neuroestrutural e nos danos neuroplásticos provocados pelo stress crónico. No primeiro objetivo desta Tese, demonstramos a importância da proteína Tau e o impacto do seu mau funcionamento, causado pelo stress, nos nichos citogénicos do cérebro adulto, com impacto na neurogénese, mas não na astrogliogénese ou oligodendrogénese; pois animais sem a proteína Tau são protegidos contra a supressão neurogénica induzida pelo stress crónico. No segundo objetivo, focamo-nos nas ações do receptor de glucocorticoides (GR) na patologia Tau induzida pelo stress, em tipos celulares específicos. Para isso, geramos murganhos P301LTau com deleção condicional de GR em neurónios ou em microglia. Os resultados mostram que o GR é necessário para a indução de danos cognitivos derivados do stress crónico. O GR neuronal é importante para a precipitação da neuropatologia da Tau bem como para a perda de espinhas apicais na zona CA1 do hipocampo. A deleção de GR na microglia levou à sua reatividade, bem como à perda de espinhas, mas com o stress crónico promoveu a sua génese. A mesma não afetou a agregação/acumulação da proteína Tau. Desta forma, concluímos que os nossos dados apontam para o importante papel do GR neuronal na meadiação da neuropatologia da Tau e identificamos o papel essencial do GR na microglia para a indução de danos cognitivos. Dado que o estilo de vida moderno expõe cada vez mais os indivíduos a altas cargas de stress, é clara a necessidade de compreender melhor a ligação entre o stress crónico e a patogénese da DA, facilitando o tratamento da DA e de outros distúrbios.The work presented in this thesis was performed in the Life and Health Sciences Research Institute (ICVS), University of Minho, Portugal and in the Institute of Biology Paris Seine (IBPS), Sorbonne University, France.
Financial Support was provided by a Ph.D. fellowship (PD/BD/127825/2016) from the FCT – Foundation for Science and Technology. This Ph.D. has also been funded by National funds, through the Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020; and by the projects, NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, the Project Estratégico co-funded by FCT (PEst-C/SAU/LA0026/2013) and the European Regional Development Fund COMPETE (FCOMP-01-0124-FEDER-037298; POCI-01-0145-FEDER-007038) supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). We acknowledge support from PAULIF, a bilateral “Luso-France Integrated Actions” program and to “France Alzheimer et Maladies Apparentées” program
Earthquake generated construction and demolition waste
No full textThe complexity of disaster effects has elevated post-disaster management to the forefront of policy debates. Earthquakes can have far-reaching consequences on a region’s economic, population health, and natural environment, all of which necessitate careful management of the massive amounts of construction and demolition waste (CDW) that result. Besides these effects, disaster waste has the potential to overwhelm already overburdened solid waste disposal facilities and interfere with emergency response and recovery efforts. Disaster waste management (DWM) is essential to overcome these problems. Substantial economic and environmental benefits, support in reconstruction, and a model for the resource usage of CDW worldwide can be expected from post-disaster waste management, safe demolition, and environmentally acceptable disposal and recycling methods for CDW. The purpose of this study is to present the findings of important case studies examining post-earthquake waste management solutions and issues. Focusing on the resources, the present work analyzes the amounts of waste created by earthquakes.(undefined