Repositório RCAAP

Historical roots of psychopathology

Mental illness and mental symptoms depend on a construction that results from the decisions of certain social agents, which, in a specific social and historical context, according to an epistemological framework (how symptoms and disorders are constructed and detected) and an ontological framework (how they are defined, what they consist of), identify the behaviors which make up a symptom or a disorder (Berrios, 2011). Only after these theoretical hypotheses of mental symptom and disorder have been outlined are the data which empirically validate them searched and found. Therefore, the objects of psychiatry (mental symptom and disorder) being the result of a social conjecture and a philosophical perspective rooted in a specific time, they should also be studied with elements from social and human sciences (history, sociology, philosophy) (Telles-Correia, 2015).

Ano

2025-10-28T12:19:09Z

Creators

Telles-Correia, Diogo Sampaio, Daniel

Rethinking Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder with insidious onset and progressive course, which prevalence increases with the age. It is characterized by neuronal degeneration and death, related to the deposition in the brain of the amyloid β1–42 peptide and the hyperphosphorylated tau protein, and initially affects brain areas, namely the hippocampus and other medial temporal lobe structures, which are important for memory processes (Blennow et al., 2006). As a consequence of the aging of the population, the number of patients with AD and other dementias, as well as the number of elderly people who, although not demented, suffer from significant cognitive decline, is growing worrisomely (Alzheimer’s Disease International, 2009).

Ano

2025-10-28T12:14:15Z

Creators

De Mendonça, Alexandre

Aplicação dos modelos lineares generalizados às telecomunicações móveis: caracterização dos clientes que desactivam os seus serviços

O mercado de telecomunicações e actualmente caracterizado por forte concorrência entre os vários operadores em actividade e por um elevado nível de saturação, sendo cada vez mais difícil a angariação de novos clientes, havendo por isso uma forte aposta na retenção e fidelização dos existentes. Por este motivo é cada vez mais importante o conhecimento do perfil do cliente, a identificação dos factores que influenciam a sua satisfação e das variáveis que o influenciam realmente na decisão de mudar de prestador de serviço ou de se manter com o actual. Com o objectivo de caracterizar os clientes que desactivam os seus serviços recolheu-se informação relativa a um segmento específico: clientes residenciais pós-pagos. A formulação de um (ou vários) modelo(s) de regressão logística - para variável resposta do tipo binário, activo ou desactivo – servirá para identificar quais são os factores que estes clientes mais valorizam e têm real impacto na sua satisfação, bem como, em oposição, identificar claramente quais os podem levar à decisão de mudar de operador, ou seja, encontrar os factores que diferenciam os clientes activos dos desactivos. Os modelos de regressão logística são um caso particular de um vasto conjunto de modelos de utilização muito ampla: os modelos lineares generalizados. Estes caracterizam-se pelo facto de poderem ter variável resposta não normal, desde que esta satisfaça a condição de ser bem ajustada por uma distribuição pertencente à familia exponencial. A ligação entre a variável resposta e o vector de covariáveis pode ser estabelecida através de uma função monótona diferenciável chamada função de ligação. É apresentado neste estudo um método de estimaçao dos parâmetros para este tipo de modelos. Sao descritas várias estratégias de modelação e comparados os resultados respectivos, sendo também descritos alguns problemas numéricos surgidos durante o processo (comuns para dados deste tipo), algumas possíveis causas e soluções.

Ano

2025-10-28T12:09:36Z

Creators

Mestre, Paula Figueiredo

Current Wildland Fire Patterns and Challenges in Europe: A Synthesis of National Perspectives

Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009–2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action “Fire and the Earth System: Science & Society” funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence

Ano

2025-10-28T12:28:46Z

Creators

Fernandez-Anez, Nieves Krasovskiy, Andrey Müller, Mortimer Vacik, Harald Baetens, Jan Hukić, Emira Kapovic Solomun, Marijana Atanassova, Irena Glushkova, Maria Bogunović, Igor Fajković, Hana Djuma, Hakan Boustras, George Adámek, Martin Devetter, Miloslav Hrabalikova, Michaela Huska, Dalibor Martínez Barroso, Petra Vaverková, Magdalena Daria Zumr, David Jõgiste, Kalev Metslaid, Marek Koster, Kajar Köster, Egle Pumpanen, Jukka Ribeiro-Kumara, Caius Di Prima, Simone Pastor, Amandine V Rumpel, Cornelia Seeger, Manuel Daliakopoulos, Ioannis Daskalakou, Evangelia Koutroulis, Aristeidis Papadopoulou, Maria P. Stampoulidis, Kosmas Xanthopoulos, Gavriil Aszalós, Réka Balázs, Deák Kertész, Miklós Valkó, Orsolya Finger, David C. Thorsteinsson, Throstur Till, Jessica Bajocco, Sofia Gelsomino, Antonio Amodio, Antonio Minervino Novara, Agata Salvati, Luca Telesca, Luciano Ursino, Nadia Jansons, Aris Kitenberga, Mara Stivrins, Normunds Brazaitis, Gediminas Marozas, Vitas Cojocaru, Olesea Gumeniuc, Iachim Sfecla, Victor Imeson, Anton Veraverbeke, Sander Mikalsen, Ragni Fjellgaard Koda, Eugeniusz Osinski, Piotr Castro, Ana C. Meira Nunes, João Pedro Oom, Duarte Vieira, Diana Rusu, Teodor Bojović, Srđan Djordjevic, Dragana Popovic, Zorica Protic, Milan Sakan, Sanja Glasa, Jan Kacikova, Danica Lichner, Lubomir Majlingova, Andrea Vido, Jaroslav Ferk, Mateja Tičar, Jure Zorn, Matija Zupanc, Vesna Hinojosa, M. Belén Knicker, Heike Lucas-Borja, Manuel Esteban Pausas, Juli Prat-Guitart, Nuria Ubeda, Xavier Vilar, Lara Destouni, Georgia Ghajarnia, Navid Kalantari, Zahra Seifollahi-Aghmiuni, Samaneh Dindaroglu, Turgay Yakupoglu, Tugrul Smith, Thomas Doerr, Stefan Cerda, Artemi

Evolution of Flavylium-Based Color Systems in Plants: What Physical Chemistry Can Tell Us

Anthocyanins are the basis of the color of angiosperms, 3-deoxyanthocyanins and sphagnorubin play the same role in mosses and ferns, and auronidins are responsible for the color in liverworts. In this study, the color system of cyanidin-3-O-glucoside (kuromanin) as a representative compound of simpler anthocyanins was fully characterized by stopped flow. This type of anthocyanin cannot confer significant color to plants without intra- or intermolecular interactions, complexation with metals or supramolecular structures as in Commelina communis. The anthocyanin's color system was compared with those of 3-deoxyanthocyanins and riccionidin A, the aglycone of auronidins. The three systems follow the same sequence of chemical reactions, but the respective thermodynamics and kinetics are dramatically different.

Ano

2025-10-28T12:13:06Z

Creators

Pina, Fernando Alejo-Armijo, Alfonso Clemente, Adelaide Mendoza, Johan Seco, André Basílio, Nuno Parola, António Jorge

Inhibition of Plasmodium liver infection by Ivermectin

Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of Plasmodium infection in vitro Notably, ivermectin potently inhibits liver infection in vivo by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission because of its effects on the mosquito vector. Our study extends the effect of ivermectin to the early stages of mammalian host infection and supports the inclusion of this multipurpose drug in malaria control strategies.

Ano

2025-10-28T12:24:20Z

Creators

Mendes, António M. Albuquerque, Inês S. Machado, Marta Pissarra, Joana Meireles, Patricia Prudêncio, Miguel

Consequences of the variability of the CovRS and RopB regulators among Streptococcus pyogenes causing human infections

To evaluate the importance of covRS and ropB mutations in invasive disease caused by Group A Streptococci (GAS), we determined the sequence of the covRS and ropB genes of 191 isolates from invasive infections and pharyngitis, comprising a diverse set of emm types and multilocus sequence types. The production of SpeB and the activity of NAD glycohydrolase (NADase) and streptolysin S (SLS) were evaluated. The results support the acquisition of null covS alleles (predicted to eliminate protein function), resulting in downregulation of SpeB and upregulation of NADase and SLS, as a mechanism possibly contributing to higher invasiveness. Among the isolates tested, this mechanism was found to be uncommon (10% of invasive isolates) and was not more prevalent among clones with enhanced invasiveness (including M1T1) but occurred in diverse genetic backgrounds. In lineages such as emm64, these changes did not result in upregulation of NADase and SLS, highlighting the diversity of regulatory pathways in GAS. Despite abrogating SpeB production, null alleles in ropB were not associated with invasive infection. The covRS and ropB genes are under stabilising selection and no expansion of isolates carrying null alleles has been observed, suggesting that the presence of these regulators is important for overall fitness.

Ano

2025-10-28T12:24:20Z

Creators

Friães, Ana Pato, Catarina Cristino, José Melo Ramirez, Mário

Transplantation tolerance: context matters

Costimulation blockade has been one of the most studied strategies to achieve immune tolerance, particularly in transplantation. Yet, in spite of the robust nature of the tolerance-inducing potential of costimulation blockade, a comprehensive understanding of the molecular and cellular mechanisms underlying tolerance induction is still missing. Nevertheless, progress has been continuously made. In this issue of the European Journal of Immunology, Chai et al. [Eur. J. Immunol. 2015. 45: 2017-2027] show that transplantation tolerance induced with an anti-CD154 monoclonal antibody relies on the coexistence of several tolerogenic mechanisms rather than one simple regulatory mechanism. These observations highlight the importance of concerted actions involving multiple pathways, namely apoptosis, acquisition of regulatory cells, or inhibition of proliferation, all of which contribute to the induction and maintenance of robust immune tolerance. A better understanding of these distinct tolerogenic pathways may lead to the development of better tolerance-inducing therapeutics.

Ano

2025-10-28T12:14:01Z

Creators

Graca, Luis

Fibras de referência em interferometria de longas distâncias: calibração e sensibilidades

A interferometria óptica coerente é uma das mais interessantes técnicas para a metrologia de comprimento. No caso específico da metrologia absoluta, sem qualquer deslocamento dos espelhos que definem os braços do interferómetro, é possível realizar medições sem ambiguidade, através da utilização de um comprimento de onda sintético resultante de um varrimento na frequência óptica. No entanto, à medida que a diferença de percurso óptico (OPD) entre braços do interferómetro aumenta, a incerteza de medição também aumenta devido à propagação da incerteza associada à medição do comprimento de onda sintético. Para contornar este problema, foi desenvolvido pelo Laboratório de Óptica, Lasers e Sistemas da Faculdade de Ciências da Universidade de Lisboa uma técnica, designada por DualFSI, onde é introduzida uma fibra longa de referência que permite diminuir a OPD para um valor muito inferior, tirando-se assim proveito das condições de medida para pequenas OPD. A técnica é baseada num duplo interferómetro que utiliza a mesma fonte e permite simultaneamente a medição de uma distância e a calibração dinâmica da fibra de referência. A calibração e caracterização da fibra de referência tem um papel fundamental no desempenho da técnica DualFSI, sendo este o principal objectivo desta tese. Neste trabalho são apresentados estudos relativos às técnicas de acoplamento, perdas de intensidade, repetibilidade e optimização do processo de acoplamento do feixe luminoso na fibra óptica, e estudos relativos à variação da polarização em função do acoplamento. Por fim, são apresentados os resultados da calibração de três fibras ópticas de referência e é comentada a sua influência no desempenho global do sistema de medição absoluta de distâncias longas.

Ano

2025-10-28T12:14:15Z

Creators

Oliveira, Vítor Manuel Agostinho Domingos de

Non‐classical major histocompatibility complex proteins as determinants of tumour immunosurveillance

Tumours develop in vertebrate organisms endowed with immune systems that are potentially able to eradicate them. Nevertheless, our ever-increasing understanding of the complex interactions between lymphocytes and tumour cells fuels the long-standing hope of developing efficient immunotherapies against cancer. This review focuses on a versatile family of proteins, the major histocompatibility complex class Ib, which has been recently implicated in both the establishment of anti-tumour immune responses and in tumour immune response evasion. We focus on a subset of class Ib proteins, human leukocyte antigen (HLA)-G, Qa-2, CD1d and NKG2D ligands, which bind to either stimulatory or inhibitory receptors expressed on T, natural killer (NK) and NKT lymphocytes, and thereby modulate their anti-tumour activity.

Ano

2025-10-28T12:28:07Z

Creators

Gomes, Anita Q. Correia, Daniel V. Silva-Santos, Bruno

Influence of systemic conditions on the incidence of periimplant pathology: a case-control study

Aim: This case-control study aimed to investigate the effect of preexisting systemic conditions on the incidence of periimplant pathology (PIP). Methods: One thousand three hundred fifty patients with dental implants were included (270 cases with PIP matched for age, gender, and time of follow-up with 1080 controls without PIP). The effect of the history of periodontitis (HP), smoking habits (SH), comorbidities, and history of chemotherapy or irradiation of the head and neck, was evaluated inferentially (χ, significance level of 5%). Crude odds ratios (OR) and attributable fraction (AF) were calculated for the variables identified as risk factors for PIP. Results: The variables HP and SH were identified as risk factors for PIP (P < 0.001) with OR = 25 and OR = 2, respectively. The AF estimated a potential of 96% and 51% reduction in the probability of PIP in the cases if the exposures to HP and SH were removed, respectively. Conclusions: Patients presenting a HP or SH had a higher probability of having PIP, whereas no significant differences were found between cases and controls for the presence of comorbidities or history of chemotherapy and irradiation of the head and neck. Through the AF, it was estimated that removing the exposure to HP and SH would result in a potential decline of at least half of the patients with PIP, which represents an important benefit for implant-supported rehabilitations.

Ano

2025-10-28T12:11:58Z

Creators

Nobre, Miguel de Araújo Maló, Paulo Antune, Elsa

Epidemiological survey of the first case of vancomycin-resistant Staphylococcus aureus infection in Europe

We report on the follow-up and epidemiological study triggered by the isolation of the first vancomycin-resistant Staphylococcus aureus (VRSA) detected in Europe. The patient and 53 close contacts were screened for S. aureus colonization and all isolates recovered were characterized by multiple molecular typing methods. The VRSA remained confined to the infected foot of the patient and was not detected in any of the close contacts. Nasal colonization with S. aureus was detected in 20 subjects, of whom 15 carried methicilin-susceptible isolates with the remaining five harbouring methicilin-resistant S. aureus (MRSA). The majority of the isolates belonged to clones that have been previously shown to be prevalent in Portugal, both in the hospital setting and in the community. Only one isolate, an MRSA, was closely related to the VRSA. Like most of the characterized VRSA isolates from other countries, the VRSA isolated in Portugal belonged to clonal complex (CC) 5. Despite the absence of VRSA dissemination, the recent increase in the incidence of lineages belonging to CC5 in some European countries, including Portugal, may result in more frequent opportunities for the emergence of VRSA.

Ano

2025-10-28T12:18:14Z

Creators

Friães, Ana Resina, C. Manuel, V. Lito, L. Ramirez, Mário Cristino, José Melo

Promastigotes of Leishmania spp. developing in human bone marrow in vitro

A 39-year-old woman with human immunodeficiency virus (HIV) infection presented with severe asthenia, abdominal painand fever of several weeks duration. Physical examination revealed hepatomegaly that was later confirmed by imaging (nosplenomegaly was observed). Leishmaniasis was suspected and abone marrow aspiration was performed. The sample was col-lected in ethylenediamine tetra-acetic acid and an immediatebone marrow film was made. The amastigote forms of Leish-mania spp. were observed inside macrophages and neutrophils (Image, May–Grünwald–Giemsa stain, 9100 objective, Day 1).

Ano

2025-10-28T12:21:14Z

Creators

Barros Pinto, Marco P. Marques, Guilhermina Cristino, José Melo

The Revised Self-Monitoring Scale detects early impairment of social cognition in genetic frontotemporal dementia within the GENFI cohort

Background: Although social cognitive dysfunction is a major feature of frontotemporal dementia (FTD), it has been poorly studied in familial forms. A key goal of studies is to detect early cognitive impairment using validated measures in large patient cohorts. Methods: We used the Revised Self-Monitoring Scale (RSMS) as a measure of socioemotional sensitivity in 730 participants from the genetic FTD initiative (GENFI) observational study: 269 mutation-negative healthy controls, 193 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. All participants underwent the standardised GENFI clinical assessment including the 'CDR® plus NACC FTLD' scale and RSMS. The RSMS total score and its two subscores, socioemotional expressiveness (EX score) and modification of self-presentation (SP score) were measured. Volumetric T1-weighted magnetic resonance imaging was available from 377 mutation carriers for voxel-based morphometry (VBM) analysis. Results: The RSMS was decreased in symptomatic mutation carriers in all genetic groups but at a prodromal stage only in the C9orf72 (for the total score and both subscores) and GRN (for the modification of self-presentation subscore) groups. RSMS score correlated with disease severity in all groups. The VBM analysis implicated an overlapping network of regions including the orbitofrontal cortex, insula, temporal pole, medial temporal lobe and striatum. Conclusions: The RSMS indexes socioemotional impairment at an early stage of genetic FTD and may be a suitable outcome measure in forthcoming trials.

Ano

2025-10-28T12:14:42Z

Creators

Franklin, Hannah D. Russell, Lucy L. Peakman, Georgia Greaves, Caroline V. Bocchetta, Martina Nicholas, Jennifer Poos, Jackie Convery, Rhian S. Cash, David M. van Swieten, John Jiskoot, Lize Miltenberger-Miltenyi, Gabriel van Minkelen, Rick Mitchell, Sara Moore, Katrina Nacmias, Benedetta Nelson, Annabel Öijerstedt, Linn Olives, Jaume Ourselin, Sebastien Padovani, Alessandro Moreno, Fermin Panman, Jessica Papma, Janne M. Pijnenburg, Yolande Polito, Cristina Premi, Enrico Prioni, Sara Prix, Catharina Rademakers, Rosa Redaelli, Veronica Rinaldi, Daisy Sanchez-Valle, Raquel Rittman, Tim Rogaeva, Ekaterina Rollin, Adeline Rosa-Neto, Pedro Rossi, Giacomina Rossor, Martin Santiago, Beatriz Saracino, Dario Sayah, Sabrina Scarpini, Elio Borroni, Barbara Schönecker, Sonja Seelaar, Harro Semler, Elisa Shafei, Rachelle Shoesmith, Christen Swift, Imogen Tábuas-Pereira, Miguel Tainta, Mikel Taipa, Ricardo Tang-Wai, David Laforce, Robert Thomas, David L. Thompson, Paul Thonberg, Hakan Timberlake, Carolyn Tiraboschi, Pietro Todd, Emily Van Damme, Philip Vandenbulcke, Mathieu Veldsman, Michele Verdelho, Ana Masellis, Mario Villanua, Jorge Warren, Jason Wilke, Carlo Woollacott, Ione Wlasich, Elisabeth Zetterberg, Henrik Zulaica, Miren Tartaglia, Maria Carmela Graff, Caroline Galimberti, Daniela Rowe, James B. Finger, Elizabeth Synofzik, Matthis Vandenberghe, Rik De Mendonça, Alexandre Tagliavini, Fabrizio Santana, Isabel Ducharme, Simon Butler, Chris Gerhard, Alex Levin, Johannes Danek, Adrian Otto, Markus Sorbi, Sandro Le Ber, Isabelle Pasquier, Florence Rohrer, Jonathan D. Afonso, Sónia Almeida, Maria Rosario Anderl-Straub, Sarah Andersson, Christin Antonell, Anna Archetti, Silvana Arighi, Andrea Balasa, Mircea Barandiaran, Myriam Bargalló, Nuria Bartha, Robart Bender, Benjamin Benussi, Alberto Bertoux, Maxime Bertrand, Anne Bessi, Valentina Black, Sandra Borrego-Ecija, Sergi Bras, Jose Brice, Alexis Bruffaerts, Rose Camuzat, Agnès Cañada, Marta Cantoni, Valentina Caroppo, Paola Castelo-Branco, Miguel Colliot, Olivier Cope, Thomas Deramecourt, Vincent de Arriba, María Di Fede, Giuseppe Díez, Alina Duro, Diana Fenoglio, Chiara Ferrari, Camilla Ferreira, Catarina B. Fox, Nick Freedman, Morris Fumagalli, Giorgio Funkiewiez, Aurélie Gabilondo, Alazne Gasparotti, Roberto Gauthier, Serge Gazzina, Stefano Giaccone, Giorgio Gorostidi, Ana Greaves, Caroline Guerreiro, Rita Heller, Carolin Hoegen, Tobias Indakoetxea, Begoña Jelic, Vesna Karnath, Hans-Otto Keren, Ron Kuchcinski, Gregory Langheinrich, Tobias Lebouvier, Thibaud Leitão, Maria João Lladó, Albert Lombardi, Gemma Loosli, Sandra Maruta, Carolina Mead, Simon Meeter, Lieke

Further investigation of harmicines as novel antiplasmodial agents: synthesis, structure-activity relationship and insight into the mechanism of action

The rise of the resistance of the malaria parasite to the currently approved therapy urges the discovery and development of new efficient agents. Previously we have demonstrated that harmicines, hybrid compounds composed from β-carboline alkaloid harmine and cinnamic acid derivatives, linked via either triazole or amide bond, exert significant antiplasmodial activity. In this paper, we report synthesis, antiplasmodial activity and cytotoxicity of expanded series of novel triazole- and amide-type harmicines. Structure-activity relationship analysis revealed that amide-type harmicines 27, prepared at N-9 of the β-carboline core, exhibit superior potency against both erythrocytic stage of P. falciparum and hepatic stages of P. berghei. Notably, harmicine 27a, m-(trifluoromethyl)cinnamic acid derivative, exhibited the most favourable selectivity index (SI = 1105). Molecular dynamics simulations revealed the ATP binding site of P. falciparum heat shock protein 90 as a druggable binding location, confirmed the usefulness of the harmine's N-9 substitution and identified favourable N-H … π interactions involving Lys45 and the aromatic phenyl unit in the attached cinnamic acid fragment as crucial for the enhanced biological activity. Thus, those compounds were identified as promising and valuable leads for further derivatization in the search of novel, more efficient antiplasmodial agents.

Ano

2025-10-28T12:10:18Z

Creators

Marinović, Marina Poje, Goran Perković, Ivana Fontinha, Diana Prudêncio, Miguel Held, Jana Pessanha de Carvalho, Lais Tandarić, Tana Vianello, Robert Rajić, Zrinka

Targeting mRNA processing as an anticancer strategy

Discoveries in the past decade have highlighted the potential of mRNA as a therapeutic target for cancer. Specifically, RNA sequencing revealed that, in addition to gene mutations, alterations in mRNA can contribute to the initiation and progression of cancer. Indeed, precursor mRNA processing, which includes the removal of introns by splicing and the formation of 3' ends by cleavage and polyadenylation, is frequently altered in tumours. These alterations result in numerous cancer-specific mRNAs that generate altered levels of normal proteins or proteins with new functions, leading to the activation of oncogenes or the inactivation of tumour-suppressor genes. Abnormally spliced and polyadenylated mRNAs are also associated with resistance to cancer treatment and, unexpectedly, certain cancers are highly sensitive to the pharmacological inhibition of splicing. This Review summarizes recent progress in our understanding of how splicing and polyadenylation are altered in cancer and highlights how this knowledge has been translated for drug discovery, resulting in the production of small molecules and oligonucleotides that modulate the spliceosome and are in clinical trials for the treatment of cancer.

Ano

2025-10-28T12:18:55Z

Creators

Desterro, Joana Bak-Gordon, Pedro Carmo-Fonseca, Maria

The role of the cell nucleus in mechanotransduction

Mechanical forces are known to influence cellular processes with consequences at the cellular and physiological level. The cell nucleus is the largest and stiffest organelle, and it is connected to the cytoskeleton for proper cellular function. The connection between the nucleus and the cytoskeleton is in most cases mediated by the linker of nucleoskeleton and cytoskeleton (LINC) complex. Not surprisingly, the nucleus and the associated cytoskeleton are implicated in multiple mechanotransduction pathways important for cellular activities. Herein, we review recent advances describing how the LINC complex, the nuclear lamina, and nuclear pore complexes are involved in nuclear mechanotransduction. We will also discuss how the perinuclear actin cytoskeleton is important for the regulation of nuclear mechanotransduction. Additionally, we discuss the relevance of nuclear mechanotransduction for cell migration, development, and how nuclear mechanotransduction impairment leads to multiple disorders.

Ano

2025-10-28T12:11:02Z

Creators

Janota, Cátia Calero-Cuenca, Francisco J. Gomes, Edgar

Feelings in the Field: The Emotional Labour of the Ethnographer

Despite the recent theoretical debate over the importance of addressing emotions in fieldwork, most European undergraduate programmes in anthropology still lack methodology courses that specifi cally focus on the emotional impact of doing research. In this article, I draw from my research with activist parents of autistic children in Portugal to explore the affective dimensions of fieldwork experience. In particular, I give an account of how I have dwelled on the emotional challenges that I faced, how these have resulted in vehicles of understanding and affected the analysis of my work as an anthropologist. While fieldwork experience always entails unexpected and surprising emotional challenges, I argue that as anthropologists we can surely benefit from more tailored support networks, safer spaces for discussion, and better pastoral care.

Ano

2025-10-28T12:18:28Z

Creators

Lo Bosco, Maria Concetta

:Estúdio, vol.7, nº14 (Abr./Jun. 2016)

Criação, da emancipação ao resgate A criação pode traduzir-se como a transformação de pensamento em coisa. Quando os materiais ganham um sentido mercê de uma reorganização, uma intenção, esses materiais podem ser lidos.A arte tem uma prerrogativa sobre a utilidade: dispensa-a ontologicamente. Mas essa utilidade contraria-se na sua materialidade: qualquer peça de arte, aclamadamente inútil no seu valor facial, encontra-se ancorada na utilidade das máquinas e dos suportes que permitem a sua exibição. Na arte contemporânea costuma ser preciso ligar um aparelho. E a arte, parecendo cada vez mais livre e emancipada, exige cada vez mais cadeias de produção, divisão do trabalho, mercadorias, utilidades. Os 17 artigos reunidos neste número 14 da revista Estúdio abrangem as relações e as distâncias, os materiais e as pessoas, os vínculos temporários que suportam novos pensamentos. Fica patente, neste itinerário pleno de ligações entre pessoas, culturas, passados e presentes, a arte: uma ligação intermitente com os objetos, os materiais, que ora se tornam vestígios, ora cifrados, ora mediatizadores de uma ligação mais profunda que radica na condição humana.

Ano

2025-10-28T12:10:04Z

Creators

Queiroz, João Salteiro, Ilidio Tosetto, Guilherme Marcondes Martins, Marta Lopes, Almerinda Radulescu De Barrio De Mendoza, Mihaela Cirillo, Aparecido José López López, Marta Grigolin Moraes, Fernanda Pérez Suárez, Ventura Alejandro García Rotger, Carmen Elena Hidalgo Valencia, Isabel García Lema, Natalia Desirée Loeck Hérnandez, Juan Corbato, Román Correia, Carlos Coimbra, Prudência Antão Nicolaiewsky, Alfredo Maneschy, Orlando Castro Silva, João Gonçalves, Luís Jorge Rodrigues Prieto, Margarida P.

:Estúdio, vol.7, nº15 (Jul./Set. 2016)

Sempre com o tema geral que orienta esta publicação, artistas a escreverem sobre outros artistas, este número 15 da revista Estúdio reuniu 17 artigos que, no seu conjunto, permitem alguma reflexão. Percebem-se, na textura das obras e dos criadores visitados, regularidades nos sentidos pesquisados e propostos. Observa-se que o assunto que ocupa os criadores se baseia numa autorreferencialidade questionadora: a arte interroga o seu próprio tecido, os seus dispositivos de legitimação, as suas convenções de disseminação, os seus cânones. Brian O’Doherty (2002) enunciou o questionamento da ideologia nos espaços de apresentação, trazendo para a discussão um suporte e uma perspetiva teóricas que, de alguma forma, permitiu compreender o enredo de algumas iniciativas conceptuais e pós conceptuais. Por seu lado, Rosalind Krauss (1979) criticou as delimitações dos espaços e dos suportes ao caracterizar o “campo expandido.” O alargamento do campo pode também incluir o seu sentido. Os artigos agora reunidos transportam algumas dessas inquietações, atualizando-as. Percebe-se que os criadores observam o campo da arte com uma intencionalidade atenta e crítica, acrescentando pontuações aos consensos, quebrando-os, não de modo gratuito, mas de modo essencial. Cria-se sentido. Neste fascículo alargamos as referências descentrando o discurso sobre os artistas, dando a palavra aos artistas. As referências, regularidades observadas indicam-nos um campo em expansão, comprometido no questionamento de suportes, convenções, deslocamentos, derivas, topografias, plataformas de interação e respetivas transgressões. O risco corre no Estúdio, atravessa as paredes, e traça um propósito fundamental, a emergência fora do centro.

Ano

2025-10-28T12:26:46Z

Creators

Queiroz, João Prieto, Margarida P. Veneroso, Maria Do Carmo De Freitas Bezerra Furtado, Sylvia Beatriz Valesini, María Silvina Parreira, Suzana Isabel Malveiro Chaves, Liana Miranda Aristimuño, Felipe Sabino, Isabel Gordeeff, Eliane Muniz Albuquerque, Isabel Sousa, Ana Matilde Diogo de Fuentes Cid, Sara Teixeira, Angela Castelo Branco Campagnaro Martins, Tatiana Barros Marins Bamonte, Joedy Luciana Grando, Angela Rito, Ana Ramos, José Artur Salteiro, Ilidio Castro Silva, João Gonçalves, Luís Jorge Rodrigues