RCAAP Repository

A influência das massas de preenchimento no processo de reintegração cromática em pintura de cavalete : estudo analítico para carnações

Losses on chromatic and preparation layers are a common problem on easel paintings. When the losses are on flesh zones, there is an additional factor of concern, since this is the region that captures the biggest attention of the art appreciator. The choice of the most appropriate filling mass formulation for this situation is a crucial step. The purpose of this investigation was to understand, how the constituent materials from filler influence chromatic reintegration and how the filling materials can be used to assist in color matching on skin areas. To reach this target, the study was directed to filling and retouching of flesh zones, using a painting as a study case, belonging to Faculdade de Belas-Artes da Universidade de Lisboa – FBAUL collection. It was selected and tested 29 filling formulations (between traditional, synthetic and ready-made formulas) being 21 not pigmented and 8 pigmented on laboratory, applied over a mockup model. The 21 not pigmented samples were covered by distinct inks, usually applied in chromatic reintegration. These samples were compared between each other, as well as the 8 pigmented fillers, on different levels of luminosity. Using non-destructive imaging and analytical techniques, were identified the differences that the tested fillers might present when interacting with the applied color. It is intended to document and understand these interactions so that the reintegration process could begin to be thought from the application of filling materials. Recognition of their influence is so far done empirically. This study is another contribution to the selection of fillers. Using color and reflectance measurement, the samples could be distinguished and classified between themselves according with their similarity, and according to a reference on the painting. After the choice of the best sample, an intervention was made at the painting, in order to confirm the methodology. Based on the results obtained with this research, a protocol was proposed, that could provide some guidelines for the conservators-restorers community, a contribution to studies on chromatic reintegration.

Year

2025-10-28T12:11:44Z

Creators

Xavier, Alexandre Ferreira

Methotrexate and low-dose prednisolone downregulate osteoclast function by decreasing receptor activator of nuclear factor-κβ expression in monocytes from patients with early rheumatoid arthritis

Objective: Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that ultimately leads to bone erosions and joint destruction. Methotrexate (MTX) slows bone damage but the mechanism by which it acts is still unknown. In this study, we aimed to assess the effect of MTX and low-dose prednisolone (PDN) on circulating osteoclast (OC) precursors and OC differentiation in patients with RA. Methods: Patients with RA before and at least 6 months after MTX therapy were analysed and compared with healthy donors. A blood sample was collected in order to assess receptor activator of NF-κβ (RANK) ligand surface expression on circulating leucocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines and OC differentiation assays were performed. Results: Classical activation markers of monocytes and RANK increased in patients with RA at baseline, compared with control healthy donors, and after MTX and low-dose PDN (MTX+PDN) exposure they decreased to control levels. Although the number of OC was not different between groups, the percentage of resorbed area and the resorbed area per pit reduced after treatment. Serum soluble receptor activator of nuclear factor-kappa (RANKL) levels increased at baseline compared with healthy donors and normalised after therapy. Conclusion: Our results suggest that MTX+PDN play an important role in downregulating OC function, which we believe occurs through the decrease in RANK surface expression in monocytes.

Year

2025-10-28T12:16:21Z

Creators

Perpétuo, Inês Pedro Caetano-Lopes, joana Rodrigues, Ana Maria Campanilho-marques, Raquel Ponte, Cristina Canhao, Helena Ainola, Mari-Mia Fonseca, João Eurico

Splicing enhances recruitment of methyltransferase HYPB-Setd2 and methylation of histone H3 Lys36

Several lines of recent evidence support a role for chromatin in splicing regulation. Here, we show that splicing can also contribute to histone modification, which implies bidirectional communication between epigenetic mechanisms and RNA processing. Genome-wide analysis of histone methylation in human cell lines and mouse primary T cells reveals that intron-containing genes are preferentially marked with histone H3 Lys36 trimethylation (H3K36me3) relative to intronless genes. In intron-containing genes, H3K36me3 marking is proportional to transcriptional activity, whereas in intronless genes, H3K36me3 is always detected at much lower levels. Furthermore, splicing inhibition impairs recruitment of H3K36 methyltransferase HYPB (also known as Setd2) and reduces H3K36me3, whereas splicing activation has the opposite effect. Moreover, the increase of H3K36me3 correlates with the length of the first intron, consistent with the view that splicing enhances H3 methylation. We propose that splicing is mechanistically coupled to recruitment of HYPB/Setd2 to elongating RNA polymerase II.

Year

2025-10-28T12:27:54Z

Creators

de Almeida, Sérgio F. Grosso, Ana Rita Koch, Frederic Fenouil, Romain Carvalho, Silvia Andrade, Jorge Levezinho, Helena Gut, Marta Eick, Dirk Gut, Ivo Andrau, Jean-Christophe Ferrier, Pierre Carmo-Fonseca, Maria

Not seeing the forest for the trees: size of the minimum spanning trees (MSTs) forest and branch significance in MST-based phylogenetic analysis

Trees, including minimum spanning trees (MSTs), are commonly used in phylogenetic studies. But, for the research community, it may be unclear that the presented tree is just a hypothesis, chosen from among many possible alternatives. In this scenario, it is important to quantify our confidence in both the trees and the branches/edges included in such trees. In this paper, we address this problem for MSTs by introducing a new edge betweenness metric for undirected and weighted graphs. This spanning edge betweenness metric is defined as the fraction of equivalent MSTs where a given edge is present. The metric provides a per edge statistic that is similar to that of the bootstrap approach frequently used in phylogenetics to support the grouping of taxa. We provide methods for the exact computation of this metric based on the well known Kirchhoff's matrix tree theorem. Moreover, we implement and make available a module for the PHYLOViZ software and evaluate the proposed metric concerning both effectiveness and computational performance. Analysis of trees generated using multilocus sequence typing data (MLST) and the goeBURST algorithm revealed that the space of possible MSTs in real data sets is extremely large. Selection of the edge to be represented using bootstrap could lead to unreliable results since alternative edges are present in the same fraction of equivalent MSTs. The choice of the MST to be presented, results from criteria implemented in the algorithm that must be based in biologically plausible models.

Year

2025-10-28T12:12:52Z

Creators

Teixeira, Andreia Sofia Monteiro, Pedro T. Carrico, Joao Andre Ramirez, Mário Francisco, Alexandre P.

Differentiated skeletal cells contribute to blastema formation during zebrafish fin regeneration

The origin of cells that generate the blastema following appendage amputation has been a long-standing question in epimorphic regeneration studies. The blastema is thought to originate from either stem (or progenitor) cells or differentiated cells of various tissues that undergo dedifferentiation. Here, we investigate the origin of cells that contribute to the regeneration of zebrafish caudal fin skeletal elements. We provide evidence that the process of lepidotrichia (bony rays) regeneration is initiated as early as 24 hours post-amputation and that differentiated scleroblasts acquire a proliferative state, detach from the lepidotrichia surface, migrate distally, integrate into the blastema and dedifferentiate. These findings provide novel insights into the origin of cells in epimorphic appendage regeneration in zebrafish and suggest conservation of regeneration mechanisms between fish and amphibians.

Year

2025-10-28T12:23:27Z

Creators

Sousa, Sara Afonso, Nuno Bensimon-Brito, Anabela Fonseca, Mariana Simões, Mariana Leon, Joaquín Roehl, Henry Cancela, Maria Leonor Jacinto, Antonio

Highly dynamic host actin reorganization around developing Plasmodium inside hepatocytes

Plasmodium sporozoites are transmitted by Anopheles mosquitoes and infect hepatocytes, where a single sporozoite replicates into thousands of merozoites inside a parasitophorous vacuole. The nature of the Plasmodium-host cell interface, as well as the interactions occurring between these two organisms, remains largely unknown. Here we show that highly dynamic hepatocyte actin reorganization events occur around developing Plasmodium berghei parasites inside human hepatoma cells. Actin reorganization is most prominent between 10 to 16 hours post infection and depends on the actin severing and capping protein, gelsolin. Live cell imaging studies also suggest that the hepatocyte cytoskeleton may contribute to parasite elimination during Plasmodium development in the liver.

Year

2025-10-28T12:17:59Z

Creators

Gomes Santos, Carina S. S. Itoe, Maurice Afonso, Cristina Henriques, Ricardo Gardner, Rui Sepulveda, Nuno Simões, Pedro D. Raquel, Maria Helena Almeida, António Paulo Moita, Luis Frischknecht, Friedrich Mota, Maria M.

Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina

Retinal homeostasis relies on intricate coordination of cell death and survival in response to stress and damage. Signaling mechanisms that coordinate this process in the adult retina remain poorly understood. Here we identify Decapentaplegic (Dpp) signaling in Drosophila and its mammalian homologue Transforming Growth Factor-beta (TGFβ) superfamily, that includes TGFβ and Bone Morphogenetic Protein (BMP) signaling arms, as central mediators of retinal neuronal death and tissue survival following acute damage. Using a Drosophila model for UV-induced retinal damage, we show that Dpp released from immune cells promotes tissue loss after UV-induced retinal damage. Interestingly, we find a dynamic response of retinal cells to this signal: in an early phase, Dpp-mediated stimulation of Saxophone/Smox signaling promotes apoptosis, while at a later stage, stimulation of the Thickveins/Mad axis promotes tissue repair and survival. This dual role is conserved in the mammalian retina through the TGFβ/BMP signaling, as supplementation of BMP4 or inhibition of TGFβ using small molecules promotes retinal cell survival, while inhibition of BMP negatively affects cell survival after light-induced photoreceptor damage and NMDA induced inner retinal neuronal damage. Our data identify key evolutionarily conserved mechanisms by which retinal homeostasis is maintained.

Year

2025-10-28T12:11:30Z

Creators

Kramer, Joshua Neves, Joana Koniikusic, Mia Jasper, Heinrich Lamba, Deepak A.

Gestão e suporte aplicacional na área de business intelligence

No âmbito do Projecto de Engenharia Informática (PEI) surgiu a oportunidade de adquirir experiência e novos conhecimentos sobre ferramentas, tecnologias e metodologias do mundo empresarial, numa das maiores empresas de Sistemas de Informação a nível nacional, a Portugal Telecom – Sistemas de Informação S.A. (PTSI). O estágio foi efectuado na área de Suporte Técnico de Business Intelligence (BI) na qual estão inseridos os maiores projectos de BI do grupo PT. Neste departamento de suporte são efectuadas tarefas como as de identificar, analisar, acompanhar, resolver todos os incidentes e problemas que surjam no âmbito de uma aplicação de BI, a instalação de software correctivo e evolutivo nos ambientes de Qualidade e Produção bem como a implementação de novas ferramentas aplicacionais de modo a garantir a operacionalidade da área com vista a automatizar os nossos processos e a diminuir os tempos de resposta aos problemas/necessidades identificados em cada aplicação. O estágio contou com o desenvolvimento de uma ferramenta para a instalação de software relativamente ao sistema de gestão de base de dados SqlServer2005, com o objectivo de automatizar e melhorar o processo de instalação de software para que houvesse uma diminuição dos tempos de resposta por parte da nossa equipa perante o cliente de negócio. A ferramenta foi elaborada seguindo todas as etapas de desenvolvimento de software impostas pelas metodologias da PTSI.

Year

2025-10-28T12:12:12Z

Creators

Fideles, Gonçalo Nuno Coelho

Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity

Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.

Year

2025-10-28T12:15:10Z

Creators

Freitas, Ana Teresa Calhau, Conceição Antunes, Gonçalo Araújo, Beatriz Bandeira, Matilde Barreira, Sofia Bazenga, Filipa Braz, Sandra Caldeira, Daniel Santos, Susana Constantino Rosa Faria, Ana Faria, Daniel Fraga, Marta Nogueira-Garcia, Beatriz Gonçalves, Lúcia Kovalchuk, Pavlo Lacerda, Luísa Lopes, Hugo Luís, Daniel Medeiros, Fábio Melo, Ana M. P. Melo-Cristino, José Miranda, Ana Pereira, Clara Pinto, Ana Teresa Pinto, João Proença, Helena Ramos, Angélica Rato, João P. R. Rocha, Filipe Rocha, Júlio César Moreira-Rosário, André Vazão, Helena Volovetska, Yuliya Guimarães, João-Tiago Pinto, Fausto J.

Th17 cells require you to chew before you swallow

How immunity is regulated at distinct epithelial tissues that vary in microbial occupancy and environmental and tissue specific cues isn't clear. Dutzan et al. (2017) report that mechanical-derived signals, not those from micro-organisms, are key to maintaining interleukin-17-expressing T helper (Th17) cells at the oral epithelia.

Year

2025-10-28T12:28:20Z

Creators

Veldhoen, Marc

Chemoradiotherapy completion and neutropenia risk in HIV patients with cervical cancer

Cervical cancer (CC) is one of the acquired immunodeficiency syndrome (AIDS) defining diseases and the human immunodeficiency virus (HIV) infection is thought to relate with increased acute toxicity of chemoradiotherapy (CRT). We investigated the effect of HIV status in the incidence of neutropenia associated with cisplatin-based CRT for CC and its impact in treatment completion. This is a single-center retrospective cohort study. Data collection was performed for all the consecutive stage Ib-IV CC women treated with cisplatin-based CRT from 2012 to 2016, and with known HIV status. Sixty-one patients were included, 6 were HIV+. HIV+ patients had a higher risk of neutropenia at any cycle during cisplatin CRT [adjusted odds ratio (OR) 7.3, 95% confidence interval (95% CI) 1.02–52.3; P = .05]. Despite the absolute differences, mean neutrophil count was nonsignificantly lower in HIV+ women, both at baseline [4455/μL (interquartile range, IQR: 1830–6689) vs 6340 (IQR: 1720–18,970) for HIV−, P = .98] and at the end of treatment [1752/μL (IQR: 1100–2930) vs 3147/μL (IQR: 920–18,390) in HIV−; P = .06]. Moreover, when considering the effect of time, CRT seems to induce a consistent drop of neutrophils in both groups (P = .229). No febrile neutropenia events occurred. In HIV+ women, there were more CT cycle delays (P = .013), patients were more prone to use granulocyte colony-stimulating factor (G-CSF; HIV+ 40.0% vs HIV− 4.0%; P = .04) and less likely to complete at least 5 cycles of cisplatin (P = .02). All patients received adequate dose of pelvic RT, regardless of HIV status. HIV+ patients have a significantly increased risk of neutropenia during CRT treatment for CC and are less likely to complete chemotherapy with cisplatin.

Year

2025-10-28T12:18:14Z

Creators

Vendrell, Ines Ferreira, Arlindo Abrunhosa-Branquinho, André Semedo, Patrícia Miguel Pulido, Catarina F. Jorge, Marília Pina, Maria Filomena Pinto, Conceição Costa, Luis

Cross-cultural adaptation and validation of the Swallowing Disturbance Questionnaire and the Sialorrhea Clinical Scale in Portuguese patients with Parkinson’s disease

Introduction: To date, no valid outcome measure has been developed in European Portuguese (EP) to evaluate the Parkinsons' Disease (PD) patients' (PwP) reports regarding their swallowing disturbances. Objectives: The aim of this study was to translate and cross-culturally adapt the Swallowing Disturbance Questionnaire (SDQ) and the Sialorrhea Clinical Scale for PD (SCS-PD) into EP and to determine its clinimetric properties in PwP. Materials and methods: The original English SDQ and SCS-PD versions were cross-culturally adapted following recommendations established in international guidelines. The validation process involved 75 PwP and 65 healthy sex- and age-matched participants. Results: The EP versions of the SDQ and SCS-PD are equivalent to the original versions (content, depth, and scoring). Statistical analyses for the SDQ tool revealed good feasibility (missing data <5%), acceptability (no floor or ceiling effects), excellent internal consistency (Cronbach´s α = 0.95), good construct validity (78.5% revealed large to moderate loadings), moderate convergent validity (r = 0.60), good divergent validity (r = 0.40), good known-groups validity (p-value < .05) and a fair sensitivity and specificity (AUC = 0.700). Statistical analyses for the SCS-PD tool shows good feasibility, reasonable acceptability (floor effect), good internal consistency (Cronbach´s α = 0.85), good construct validity (85.7% showed between large to moderate loadings), good convergent validity (r = 0.78), good divergent validity (r = 0.39), good known groups validity (p-value < .05) and a fair sensitivity and specificity (AUC = 0.704). Conclusions: The EP versions of the SDQ and SCS-PD maintained the characteristics of the original versions and therefore consistent tools to be used in PwP.

Year

2025-10-28T12:08:41Z

Creators

Cardoso, Rita Guimarães, Isabel Santos, Helena Carvalho, Joana Abreu, Daisy Gonçalves, Nilza Ferreira, Joaquim J

Electrodiagnosis of Amyotrophic Lateral Sclerosis: a review of existing guidelines

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper motor neurons in the motor cortex and lower motor neurons (LMN) in the brainstem and spinal cord, resulting in a progressive functional impairment. Neurophysiology is a diagnostic tool to detect dysfunction of upper motor neurons and LMN, even when the changes are subclinical. Electromyography is the standard neurophysiological investigation to detect LMN changes, which is essential to exclude mimicking disorders and attain early diagnosis. Recently, Awaji criteria was proposed to support ALS diagnosis, in these criteria fasciculation potentials associated with neurogenic motor unit potentials represents a sufficient marker of LMN involvement, in each muscle. Many studies have confirmed that Awaji criteria are more sensitive, permitting earlier diagnosis without loss of specificity when compared with the revised El Escorial criteria. Fasciculations are easily detected by ultrasound; increasingly, this technique has been used to diagnose ALS, combined with electromyography. This combination can increase diagnostic accuracy. Many techniques for estimating the number of motor units have been proposed, they are useful to quantify LMN loss. Electrical impedance myography is an emerging technique with great potential to monitor ALS progression. Neurophysiological investigation of upper motor neuron dysfunction is difficult in ALS, detecting decreased cortical inhibition by threshold tracking cortical magnetic stimulation is a promising method, which needs to be validated in different centers.

Year

2025-10-28T12:13:47Z

Creators

Carvalho, Mamede

Kinematic and clinical outcomes to evaluate the efficacy of a multidisciplinary intervention on functional mobility in Parkinson's disease

Introduction: Functional mobility (FM) is a concept that incorporates the capacity of a person to move independently and safely to accomplish tasks. It has been proposed as a Parkinson's disease (PD) functional and global health outcome. In this study, we aimed to identify which kinematic and clinical outcomes changes better predict FM changes when PD patients are submitted to a specialized multidisciplinary program. Methods: PD patients engaged in a pre-defined specialized multidisciplinary program were assessed at admission and discharge. Change from baseline was calculated for all kinematic and clinical outcomes, and Timed Up and Go (TUG) was defined as the primary outcome for FM. A stepwise multivariate linear regression was performed to identify which outcome measures better predict TUG changes. Results: Twenty-four patients were included in the study. The changes in TUG Cognitive test, supervised step length, and free-living (FL) step time asymmetry were identified as the best predictors of TUG changes. The supervised step length and FL step time asymmetry were able to detect a small to moderate effect of the intervention (d values ranging from -0.26 to 0.42). Conclusions: Our results support the use of kinematic outcome measures to evaluate the efficacy of multidisciplinary interventions on PD FM. The TUG Cognitive, step length, and FL step time asymmetry were identified as having the ability to predict TUG changes. More studies are needed to identify the minimal clinically important difference for step length and FL step time asymmetry in response to a multidisciplinary intervention for PD FM.

Year

2025-10-28T12:13:47Z

Creators

Bouça-Machado, Raquel Branco, Diogo Fonseca, Gustavo Fernandes, Raquel Abreu, Daisy Guerreiro, Tiago Ferreira, Joaquim J

Vasculitis and breast cancer: mind the hint

Diffuse alveolar haemorrhage related to an anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis is an extremely rare form of presentation of breast cancer. Here we report the case of a 77-year-old woman with a histological diagnosis of a papillary ductal carcinoma of the breast presenting with a diffuse alveolar haemorrhage secondary to a perinuclear ANCA-associated vasculitis. To our knowledge, this is the first case ever reported of a diffuse alveolar haemorrhage related to an ANCA-associated small vessel vasculitis as a form of presentation of breast cancer. The therapeutic approach of this paraneoplastic vasculitis included the use of corticosteroids and plasmapheresis, a very useful technique to remove endothelial aggressors (circulating antibodies) as a strategy to earn time for a proper therapeutic decision specifically directed for disease modification, but that can also be associated with several severe adverse effects, which are illustrated in our case.

Year

2025-10-28T12:12:39Z

Creators

Esperança Martins, Miguel Evangelista, Vasco Fernandes, Salomão Almeida, Raquel

A non-infectious uveitis multidisciplinary clinic in a tertiary referral center: clinical impact and added value

Non-infectious uveitis (NIU) is a group of sight-threatening diseases that generates significant burden for the healthcare systems due to its adverse outcomes, irreversible structural complications in the eye with loss of visual function, limited clinical expertise and low-grade evidence for best practice. The usefulness of multidisciplinary care, specifically close collaboration between Rheumatologists and Ophthalmologists in NIU, has been emphasized in the literature. In this paper, the assessment tools and protocols used in our clinic are depicted and an overview of our activity with a brief description of the patients included in our registry, between 2018 and 2020 is provided. The cohort of 290 patients assessed in our NIU clinic, their demographics, sources of referral, details about immunosuppression treatment, and internal and external collaborations is described. This experience-based manuscript aims to describe the general functioning of our multidisciplinary NIU clinic, highlighting the benefits and drawbacks of multidisciplinary team management in patients with NIU, ultimately initiating a dialogue on what an NIU clinic should be and providing information for newly NIU clinics start-up. In conclusion, establishing a standardized and multidisciplinary clinic in NIU allows to systematically observe and follow-up this infrequent disease at a tertiary hospital level, thus improving quality of care delivery and research avenues.

Year

2025-10-28T12:11:58Z

Creators

Leal, Ines Romão, Vasco C. Sousa Mano, Sofia Khmelinskii, Nikita Campanilho-Marques, Raquel Ponte, Cristina Macieira, Carla Oliveira Ramos, Filipa Vieira De Sousa, Elsa Cristina Rosa, Carlos Miranda Rodrigues, Walter Pinto, Luis Marques-Neves, Carlos Fonseca, João Eurico

MPV17 mutations are associated with a quiescent energetic metabolic profile

Mutations in the MPV17 gene are associated with hepatocerebral form of mitochondrial depletion syndrome. The mechanisms through which MPV17 mutations cause respiratory chain dysfunction and mtDNA depletion is still unclear. The MPV17 gene encodes an inner membrane mitochondrial protein that was recently described to function as a non-selective channel. Although its exact function is unknown, it is thought to be important in the maintenance of mitochondrial membrane potential (ΔΨm). To obtain more information about the role of MPV17 in human disease, we investigated the effect of MPV17 knockdown and of selected known MPV17 mutations associated with MPV17 disease in vitro. We used different approaches in order to evaluate the cellular consequences of MPV17 deficiency. We found that lower levels of MPV17 were associated with impaired mitochondrial respiration and with a quiescent energetic metabolic profile. All the mutations studied destabilized the protein, resulting in reduced protein levels. We also demonstrated that different mutations caused different cellular abnormalities, including increased ROS production, decreased oxygen consumption, loss of ΔΨm, and mislocalization of MPV17 protein. Our study provides novel insight into the molecular effects of MPV17 mutations and opens novel possibilities for testing therapeutic strategies for a devastating group of disorders.

Year

2025-10-28T12:26:34Z

Creators

Jacinto, Sandra Guerreiro, Patrícia de Oliveira, Rita Machado Cunha-Oliveira, Teresa Santos, Maria João Grazina, Manuela Rego, Ana Cristina Outeiro, Tiago

MRI data-driven algorithm for the diagnosis of behavioural variant frontotemporal dementia

Introduction: Structural brain imaging is paramount for the diagnosis of behavioural variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis. Methods: A total of 515 subjects from two different bvFTD cohorts (training and independent validation cohorts) were used to perform voxel-wise morphometric analysis to identify regions with significant differences between bvFTD and controls. A random forest classifier was used to individually predict bvFTD from deformation-based morphometry differences in isolation and together with semantic fluency. Tenfold cross validation was used to assess the performance of the classifier within the training cohort. A second held-out cohort of genetically confirmed bvFTD cases was used for additional validation. Results: Average 10-fold cross-validation accuracy was 89% (82% sensitivity, 93% specificity) using only MRI and 94% (89% sensitivity, 98% specificity) with the addition of semantic fluency. In the separate validation cohort of definite bvFTD, accuracy was 88% (81% sensitivity, 92% specificity) with MRI and 91% (79% sensitivity, 96% specificity) with added semantic fluency scores. Conclusion: Our results show that structural MRI and semantic fluency can accurately predict bvFTD at the individual subject level within a completely independent validation cohort coming from a different and independent database.

Year

2025-10-28T12:14:15Z

Creators

Manera, Ana L Dadar, Mahsa Van Swieten, John Cornelis Borroni, Barbara Sanchez-Valle, Raquel Moreno, Fermin Laforce Jr, Robert Graff, Caroline Synofzik, Matthis Galimberti, Daniela Rowe, James Benedict Masellis, Mario Tartaglia, Maria Carmela Finger, Elizabeth Vandenberghe, Rik De Mendonça, Alexandre Tagliavini, Fabrizio Santana, Isabel Butler, Christopher R Gerhard, Alex Danek, Adrian Levin, Johannes Otto, Markus Frisoni, Giovanni Ghidoni, Roberta Sorbi, Sandro Rohrer, Jonathan Daniel Ducharme, Simon Collins, D Louis

What is the relationship between diversity and species diversity from the local to the regional scale?

A região mediterrânica é reconhecida pela sua riqueza e diversidade biológica, sendo um hotspot de biodiversidade (Myers e tal., 2000; Blondel e tal., 2010). As paisagens na bacia do Mediterrâneo estão actualmente sujeitas a um conjunto de dinâmicas de alterações causadas pelas actividades humana, em que se destacam a intensificação agrícola e florestal e o abandono agrícola (Proença e Pereira, 2010). Estas alterações de paisagem causam alterações aos habitats e afectam as espécies que os habitam (Blondel, 2006; Sirami e tal., 2010; Gonzáles-Megías e tal., 2011). Assim, é fundamental perceber quais as respostas das diferentes espécies a estas alterações de habitat e qual a sua capacidade de adaptação, e como essas respostas se traduzem a diferentes escalas espaciais. A relação entre o número de espécies que habita uma área e a dimensão dessa área é dos padrões mais estudados em ecologia, sendo designada como a relação espécies-área (Arrhenius, 1921). A relação espécies-área tem sido largamente verificada para vários sistemas naturais, no entanto, num contexto de alteração da paisagem e dos habitats nativos, a relação espécies-área apresenta limitações ao assumir que todo o habitat é uniforme e contínuo. Uma vez que as espécies reagem diferentemente às alterações de habitat (Tews e tal., 2004), é necessário integrar o efeito da área com o efeito de habitat. Aliás, vários estudos têm-se debruçado sobre o efeito que a diversidade de habitats tem sobre a diversidade de espécies (Williamson, 1988; Tjorve, 2002; Desrochers et al. 2011) O modelo da relação espécies-área “countryside, proposto por Pereira e Daily (2006), considera não só a existência de diferentes habitats na paisagem mas também o uso diferencial dos mesmos pelos diferentes grupos de espécies. Neste contexto, o presente trabalho, tentou responder às seguintes questões: (I) Será a heterogeneidade de habitats um proxy para a diversidade de espécies? (II) É o efeito da área e o efeito da diversidade de habitats na riqueza de espécies, dependente da escala ou dependente nas características de cada grupo de espécies? Para responder a estas questões, utilizou-se a Península Ibérica como caso de estudo e analisaram-se os padrões de diversidade de passeriformes, répteis e anfíbios à escala da grelha de 10x10 Km2, testando a influência de três classes de variáveis ambientais: uso do solo, variáveis climáticas e topográficas. No caso dos passeriformes, analisou-se diversidade de cada grupo de espécies com afinidades similares para os diferentes habitats, tendo-se para isso procedido à classificação das espécies em cada um destes grupos previamente. Para responder à questão (I) realizámos uma série de análises. A relação entre os diferentes grupos de espécies e os vários preditores ambientais foi avaliada utilizando análises de correlação (Spearman´s rho). A importância relativa dos diferentes grupos de preditores (climáticos, topográficos e de habitat) na distribuição da riqueza específica foi avaliada com uma abordagem multi-modelo, onde em cada modelo de regressão linear foram considerados várias combinações de preditores (Tabela 2). A relação entre riqueza específica e a estrutura da paisagem (heterogeneidade) para Espanha, foi avaliada através de correlação de Spearman´s e análise visual de boxplots. Para responder à segunda questão (II) comparámos o desempenho do modelo espécies-área clássico (eqn 1) com o modelo countryside-SAR (eqn 2 e 3) à escala regional. O desempenho dos modelos foi comparado usando o Akaike Information Criterion (AIC) e o Root Mean Squared Error (RMSE). Todas as análises foram efectuadas no programa R (http://www.r-project.org/). Os mapas da riqueza específica construídos para a Península Ibérica mostram que a distribuição das espécies não é homogénea, e que depende do taxon (Figura 3). Cada taxon respondeu diferentemente às variáveis ambientais testadas (Tabela 3). Todos os grupos de espécies, excepto o grupo de passeriformes com afinidade para habitats agrícolas, reagiram negativamente à presença de áreas agrícolas. Todos os grupos de espécies de passeriformes mostraram uma relação negativa com a presença de floresta exótica. Estes resultados estão em acordo com outros trabalhos que mostraram que muitas espécies tendem a evitar áreas de cultivo intensivo e plantações (Diáz e tal., 1998; Donald e tal., 2001; Benton e tal, 2003). O clima revelou-se o factor principal na determinação da diversidade das espécies. No entanto, quando as variáveis de habitat são adicionadas aos modelos de regressão com variáveis climáticas, o poder explicativo dos padrões de diversidade melhora significativamente (Tabela 4). Encontrámos também uma relação entre a heterogeneidade da paisagem e a diversidade para vários grupos taxonómicos. A dominância das variáveis climáticas não surpreende dado que a esta escala regional (10x10km2) os modelos de distribuição de espécies têm usado com sucesso apenas variáveis climáticas (Wisz e Guisan 2009), mas diverge de padrões encontrados à escala local, em que a estrutura dos habitats parece ser o factor mais relevante (Atauri e Lucio, 2001; Nogués e Martínez 2004; Moreno e Pizarro, 2007). A variedade de respostas à heterogeneidade da paisagem, pelos diferentes grupos (Tabela 5, Figura 4), indica que as espécies (i.e., os grupos de espécies), usam a paisagem de diferente modo. A diversidade de espécies num habitat está ligada com a sua capacidade de fornecer as estruturas necessárias para a sua sobrevivência, zonas de predação, refugio, reprodução, etc. (Keitt e tal, 1997; Mazerolle e Villard, 1999; Atuari e Lucio, 2001; Gil-Tena e tal., 2007; Desroches e tal 2011). A comparação do modelo clássico espécies-área com o modelo countryside demonstra que, numa paisagem multi-habitat à escala regional, o modelo countryside é o que melhor explica a riqueza específica de cada um dos grupos de espécies e do total número de espécies (Tabela 6). Para investigar o efeito da escala, os resultados foram comparados com os obtidos a escala local em estudos com plantas e aves, por Proença (2009) e Guilherme (2009), respectivamente. Em ambos os trabalhos constatou-se que o modelo countryside explicava melhor os padrões espécies-área à escala da paisagem. À semelhança do encontrado à escala regional, o parâmetro de afinidade para o habitat preferencial apresentou o valor máximo em cada grupo de espécies. No entanto, enquanto na escala local os grupos de espécies apresentaram valores de afinidade significativos para os habitats alternativos, à escala regional apenas as espécies florestais mostraram afinidades baixas para os habitats alternativos.

Year

2025-10-28T12:18:28Z

Creators

Martins, Inês Isabel Santos, 1988-

Effect of education on cognitive performance in patients with mild cognitive impairment

This study aims to investigate if education (as a cognitive reserve proxy) modifies the profile of cognitive performance. We hypothesize that participants with higher education can remain functional (due to a better executive performance), despite a more severe memory impairment, compared with lower education individuals. One hundred and sixty-six mild cognitive impairment (MCI) individuals with at least one comprehensive neuropsychological evaluation were included in a retrospective, cross-sectional study and divided into two groups (Low Education-LE [1-4 years] and Medium-to-High Education-MHE [> 4 years]). A total of 22 neuropsychological measures were analyzed. Age-adjusted results were subject to simple regression analyses to determine the variance explained by education. Average scores and proportions of low performances were subject to group comparison. The results showed similar cognitive decline patterns between individuals with LE and MHE, with no significant difference in each cognitive domain. However, MHE revealed a steeper decline in certain cognitive domains, such as sustained attention and episodic memory, compared with the LE. Moreover, MHE showed a trend to higher proportion of tests affected when compared to LE. These suggest that individuals with higher education may remain in a MCI stage despite a more widespread cognitive impairment, reflecting a higher cognitive reserve.

Year

2025-10-28T12:16:21Z

Creators

Godinho, Filipe Maruta, Carolina Borbinha, Cláudia Martins, Isabel Pavão