Repositório RCAAP
CD44v6 high membranous expression is a predictive marker of therapy response in gastric cancer patients
In gastric cancer (GC), biomarkers that define prognosis and predict treatment response remain scarce. We hypothesized that the extent of CD44v6 membranous tumor expression could predict prognosis and therapy response in GC patients. Two GC surgical cohorts, from Portugal and South Korea (n = 964), were characterized for the extension of CD44v6 membranous immuno-expression, clinicopathological features, patient survival, and therapy response. The value of CD44v6 expression in predicting response to treatment and its impact on prognosis was determined. High CD44v6 expression was associated with invasive features (perineural invasion and depth of invasion) in both cohorts and with worse survival in the Portuguese GC cohort (HR 1.461; 95% confidence interval 1.002-2.131). Patients with high CD44v6 tumor expression benefited from conventional chemotherapy in addition to surgery (p < 0.05), particularly those with heterogeneous CD44v6-positive and -negative populations (CD44v6_3+) (p < 0.007 and p < 0.009). Our study is the first to identify CD44v6 high membranous expression as a potential predictive marker of response to conventional treatment, but it does not clarify CD44v6 prognostic value in GC. Importantly, our data support selection of GC patients with high CD44v6-expressing tumors for conventional chemotherapy in addition to surgery. These findings will allow better stratification of GC patients for treatment, potentially improving their overall survival.
2025-10-28T12:27:27Z
Almeida, Gabriela M Pereira, Carla Park, Ji-Hyeon Lemos, Carolina Campelos, Sofia Gullo, Irene Martins, Diana Gonçalves, Gilza Leitão, Dina Neto, João Luís André, Ana Borges, Clara Almeida, Daniela Lee, Hyuk-Joon Kong, Seong-Ho Kim, Woo Ho Carneiro, Fátima Almeida, Raquel Yang, Han-Kwang Oliveira, Carla
Maternal sensitivity and mother-infant attachment are associated with antibiotic uptake in infancy
Attachment security has been associated with health status and symptom reporting. In this longitudinal study, we investigated the association between antibiotics uptake by infants at 9-months and mother-infant attachment at 12-months. Logistic regression analyses indicated that lower maternal sensitivity was associated with increased odds of antibiotic uptake. Furthermore, 89.7% of insecure-ambivalent infants consumed antibiotics, which contrasted with 32.5% of avoidant infants and 21.5% of secure infants. This study suggests that maternal behavior and mother-infant attachment impact on antibiotic consumption, which is worrying because antibiotics may lead to several health problems later in life and antibiotic-resistance.
2025-10-28T12:13:20Z
Fuertes, Marina Gonçalves, Joana L Faria, Anabela Lopes-dos-Santos, Pedro Conceição, Inês C Dionisio, Francisco
Trypanosoma brucei triggers a broad immune response in the adipose tissue
Adipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2-5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this study, we tested whether the AT environment responds immunologically to the presence of the parasite. Transcriptome analysis of T. brucei infected adipose tissue revealed that most upregulated host genes are involved in inflammation and immune cell functions. Histochemistry and flow cytometry confirmed an increasingly higher number of infiltrated macrophages, neutrophils and CD4+ and CD8+ T lymphocytes upon infection. A large proportion of these lymphocytes effectively produce the type 1 effector cytokines, IFN-γ and TNF-α. Additionally, the adipose tissue showed accumulation of antigen-specific IgM and IgG antibodies as infection progressed. Mice lacking T and/or B cells (Rag2-/-, Jht-/-), or the signature cytokine (Ifng-/-) displayed a higher parasite load both in circulation and in the AT, demonstrating the key role of the adaptive immune system in both compartments. Interestingly, infections of C3-/- mice showed that while complement system is dispensable to control parasite load in the blood, it is necessary in the AT and other solid tissues. We conclude that T. brucei infection triggers a broad and robust immune response in the AT, which requires the complement system to locally reduce parasite burden.
2025-10-28T12:11:16Z
Machado, Henrique Rebelo, Tiago Sequeira, Mariana Trindade, Sandra Carvalho, Tânia Rijo-Ferreira, Filipa Rentroia-Pacheco, Barbara Serre, Karine Figueiredo, Luisa M.
Variation and Selection in the Putative Sperm-Binding Region of ZP3 in Muroid Rodents: A Comparison between Cricetids and Murines
In mammals, the zona pellucida glycoprotein 3 (ZP3) is considered a primary sperm receptor of the oocyte and is hypothesized to be involved in reproductive isolation. We investigated patterns of diversity and selection in the putative sperm-binding region (pSBR) of mouse ZP3 across Cricetidae and Murinae, two hyperdiverse taxonomic groups within muroid rodents. In murines, the pSBR is fairly conserved, in particular the serine-rich stretch containing the glycosylation sites proposed as essential for sperm binding. In contrast, cricetid amino acid sequences of the pSBR were much more variable and the serine-rich motif, typical of murines, was generally substantially modified. Overall, our results suggest a general lack of species specificity of the pSBR across the two muroid families. We document statistical evidence of positive selection acting on exons 6 and 7 of ZP3 and identified several amino acid sites that are likely targets of selection, with most positively selected sites falling within or adjacent to the pSBR.
2025-10-28T12:30:03Z
Duarte, Margarida Alexandra Fernandes, C Heckel, Gerald da Luz Mathias, Maria Bastos-Silveira, Cristiane
A changing Amazon rainforest: Historical trends and future projections under post-Paris climate scenarios
Despite the progress in sustainable development strategies, the role of the Amazon rainforest as a carbon sink faces increasing disturbances that may have a critical impact on global climate. Understanding the vulnerability of the Amazon rainforest to climate change is a major challenge, considering the complex interaction between human and natural systems. This paper aims, via an interdisciplinary approach, to assess the observed evolution and possible future of the Amazon rainforest, considering different global climate and socio-economic scenarios. By comparing historical with plausible future developments, we present key knowledge to inform mitigation and regional adaptation policy considerations. As an entry point, historical trends of annual mean temperature and precipitation were analysed. In a second step, the same assessment was made for the mean annual NDVI sum (a proxy of yearly plant productivity), representing vegetation strength. For these purposes, a 34-year period (1982–2015) was considered. Trends were analysed based on non-parametric Mann-Kendall and Sen's methods. With this representation of the past, the next step focused on future scenarios. The most plausible global emission pathways were evaluated via the comparison of ten assessments of the possible effects of the mitigation action plans of national governments, as stated in the National Determined Contributions (NDCs). Results indicate a strong consensus that if either current policies, unconditional or conditional NDCs are fulfilled, the limit of global warming by “well below 2 °C” will be exceeded. In this context, climate projections for the Amazon suggest, among other results, an increase in the range of 1.3 °C (lower limit under SSP1-2.6) to 6.5 °C (upper limit under SSP5-8.5). Unlike temperature, positive and negative anomalies are expected for precipitation depending on location. Despite the uncertainty regarding the projections, possible changes such as forest diebacks and savannization may take place, namely in southeastern Amazon, by the end of the century. Overall, this study highlights the importance of carefully considering the combination of different factors, such as deforestation, to guarantee rainforest resilience under climate-driven changes.
2025-10-28T12:21:01Z
Carvalho, S.C.P. Oliveira, André Pedersen, Jiesper Strandsbjerg Tristan Manhice, Halaze Lisboa, Filipe Norguet, Jérémy de Wit, Fronika Santos, Filipe Duarte
A sink host allows a specialist herbivore to persist in a seasonal source
In seasonal environments, sinks that are more persistent than sources may serve as temporal stepping stones for specialists. However, this possibility has to our knowledge, not been demonstrated to date, as such environments are thought to select for generalists, and the role of sinks, both in the field and in the laboratory, is difficult to document. Here, we used laboratory experiments to show that herbivorous arthropods associated with seasonally absent main (source) habitats can endure on a suboptimal (sink) host for several generations, albeit with a negative growth rate. Additionally, they dispersed towards this host less often than towards the main host and accepted it less often than the main host. Finally, repeated experimental evolution attempts revealed no adaptation to the suboptimal host. Nevertheless, field observations showed that arthropods are found in suboptimal habitats when the main habitat is unavailable. Together, these results show that evolutionary rescue in the suboptimal habitat is not possible. Instead, the sink habitat functions as a temporal stepping stone, allowing for the persistence of a specialist when the source habitat is gone.
2025-10-28T12:27:54Z
Laska, Alicja Magalhaes, S Lewandowski, Mariusz Puchalska, Ewa Karpicka-Ignatowska, Kamila Radwańska, Anna Meagher, Shawn Kuczyński, Lechosław Skoracka, Anna
Multiple glacial refugia and contemporary dispersal shape the genetic structure of an endemic amphibian from the Pyrenees
Historical factors (colonization scenarios, demographic oscillations) and contemporary processes (population connectivity, current population size) largely contribute to shaping species’ present-day genetic diversity and structure. In this study, we use a combination of mitochondrial and nuclear DNA markers to understand the role of Quaternary climatic oscillations and present-day gene flow dynamics in determining the genetic diversity and structure of the newt Calotriton asper (Al. Dugès, 1852), endemic to the Pyrenees. Mitochondrial DNA did not show a clear phylogeographic pattern and presented low levels of variation. In contrast, microsatellites revealed five major genetic lineages with admixture patterns at their boundaries. Approximate Bayesian computation analyses and linear models indicated that the five lineages likely underwent separate evolutionary histories and can be tracked back to distinct glacial refugia. Lineage differentiation started around the Last Glacial Maximum at three focal areas (western, central and eastern Pyrenees) and extended through the end of the Last Glacial Period in the central Pyrenees, where it led to the formation of two more lineages. Our data revealed no evidence of recent dispersal between lineages, whereas borders likely represent zones of secondary contact following expansion from multiple refugia. Finally, we did not find genetic evidence of sex-biased dispersal. This work highlights the importance of integrating past evolutionary processes and present-day gene flow and dispersal dynamics, together with multilocus approaches, to gain insights into what shaped the current genetic attributes of amphibians living in montane habitats.
2025-10-28T12:21:54Z
Lucati, Federica Poignet, Manon Miró, Alexandre Trochet, Audrey Aubret, Fabien Barthe, Laurent Bertrand, Romain Buchaca, Teresa Calvez, Olivier Caner, Jenny Darnet, Elodie Denoël, Mathieu Guillaume, Olivier Le Chevalier, Hugo Martínez‐Silvestre, Albert Mossoll‐Torres, Marc O’Brien, David Osorio, Víctor Pottier, Gilles Richard, Murielle Sabás, Ibor Souchet, Jérémie Tomàs, Jan Ventura, Marc
Aspectos fisiológicos da insulina e seu receptor em neurónios do hipocampo
O papel da insulina e do seu receptor (InsR) no cérebro é ainda obscuro conhecendo-se contudo funções importantes na aprendizagem e na memória; aponta-se também para uma associação entre doença de Alzheimer (DA) e a Diabetes. Sabe-se igualmente que a insulina controla a neuroexcitabilidade em neurónios específicos. No nosso laboratório demonstrou-se que a insulina inibe a componente lenta- Islow das correntes de K+ activadas-por-voltagem em neurónios piramidais da zona CA1 do hipocampo de ratos. Tal efeito é observado unicamente em neurónios provenientes de animais em período pós-prandial (e não em jejum). Este trabalho propõe (a) identificar o canal de K+ sensível à insulina nestes neurónios; (b) investigar os fenómenos fisiológicos subjacentes à referida diferença observada entre" preparações em jejum" e "em pós-prandial". Recorreu-se à técnica whole-cell voltage-clamp e a técnicas de western-blotting e imunocitoquímica com anticorpos contra InsR e o canal de K+ candidato. Registos de corrente revelaram que a Margatoxina (bloqueador especifico de canais K+ tipo-KV1.3) inibe também especificamente Islow (EC50=125 pM), alterando a dependência da activação à voltagem. Experiências com tratamentos articulados de insulina e várias concentrações de margatoxina indicam o canal Kv1.3 como o responsável pelo efeito da insulina nos neurónios CA1. Demonstrou-se, por electrofisiologia e por western-blot, que a expressão do InsR é maior no período de pós-prandial. Mostra-se ainda que o canal Kv1.3 é mais expresso em ―hipocampos em pós-prandial‖ e assim postula-se uma oscilação na expressão do InsR e do canal Kv1.3 durante o ciclo jejum/pós-prandial. Finalmente, usando amostras de cérebro de ratos-modelo obesos (OZR) e diabéticos (ZDF), verificou-se que a expressão do InsR nestes dois é inferior à do controlo, o que atribui protagonismo ao cérebro no contexto das diabetes. Assim, a insulina- neural controla a neuroactividade num processo dependente do ciclo alimentar. Questiona-se consequentemente a ideia do cérebro como uma entidade isolada dos ciclos metabólicos.
2025-10-28T12:22:34Z
Mondragão, Miguel Angelo Segão
Mediterranean salt marsh sediment metal speciation and bioavailability changes induced by the spreading of non-indigenous Spartina patens
Within the Tejo Estuary, non-indigenous species (NIS) Spartina patens colonizes the upper middle marsh competing with the native Halimione portulacoides for space and resources. Due to the very different root system and metabolism between both species, this invasion can have significant biogeochemical implications, namely in terms of metal speciation and availability. In the present study, we evaluate the biogeochemical modifications in terms of metal speciation introduced by the colonization of the NIS S. patens. Total metals Cu, Zn, Pb and As within the rhizosediment varied between the two study species but was generally higher in the rhizosediment of H. portulacoides. These differences could be attributed to the higher organic content and smaller sand fraction found in the rhizosediment of H. portulacoides. Zinc was found to have highest concentration (H. portulacoides 126.22 mg g−1, S. patens 68.35 mg g−1) in the rhizosediments while Cu and As were least concentrated metals. Considering the bioavailable fractions (F1 + F2) Cu, Zn and As were more readily available in the sediment beneath NIS S. patens than in H. portulacoides and Pb presented no significance (p = 0.835). Overall, H. portulacoides rhizosediments had higher total metal concentration, whilst the rhizosediments of NIS S. patens presented a higher percentage of bioavailable metals. Thus, the bioinvasion and expansion of NIS S. patens may have implications for metal biogeochemistry and the natural remediation capacity of salt marshes in estuaries along the Mediterranean and North-eastern Atlantic coasts, as well as ensuing biodiversity and potential trophic web contamination consequences.
2025-10-28T12:13:47Z
Human, Lucienne R.D. Feijão, Eduardo Cruz De Carvalho, Ricardo Caçador, Isabel Reis-Santos, Patrick Fonseca, Vanessa Duarte, Bernardo
Long-term persistence of conservation-reliant species: Challenges and opportunities
“Conservation-reliant species” – those fully dependent on continued management actions – are booming and, with limited conservation budgets, securing funds to sustain their long-term viability is becoming overwhelming. This study assesses the degree of dependence on conservation actions of two obligatory cavity-nesters, the Lesser Kestrel Falco naumanni and the European Roller Coracias garrulus, whose populations in Europe were recently recovered through artificial nest-site provisioning. Using long-term monitoring data and population surveys conducted in their main Portuguese stronghold, we examined temporal changes in the availability and use of semi-natural (cavities in rural abandoned buildings) and artificial nest-sites. We further assessed the financial costs of nest-site provisioning and evaluated the potential use of tourism revenues as a conservation funding source. Following the implementation of conservation projects, the Lesser Kestrel and Roller populations have been increasing but >65% of all breeding pairs currently nest in artificial nest-sites. Semi-natural nest-sites remain suitable for approximately 30 years and are expected to disappear by the end of this century. Lesser Kestrels and Rollers will thus become fully dependent on artificial nest-sites and sustaining their current population sizes is estimated to cost 4500€ per year. This represents <1% of the region's lodging income, largely supported by nature-based tourism. Our findings suggest that reactive conservation measures can be very effective at recovering endangered populations but can make them fully reliant on the perpetuation of those measures. This demands long-term funding, which can be alleviated by tourism revenues in areas with high nature capital values.
2025-10-28T12:14:28Z
Gameiro, João Franco, Aldina M.A. Catry, Teresa Palmeirim, Jorge Catry, Inês
River ecosystem conceptual models and non‐perennial rivers: A critical review
Conceptual models underpin river ecosystem research. However, current models focus on continuously flowing rivers and few explicitly address characteristics such as flow cessation and drying. The applicability of existing conceptual models to nonperennial rivers that cease to flow (intermittent rivers and ephemeral streams, IRES) has not been evaluated. We reviewed 18 models, finding that they collectively describe main drivers of biogeochemical and ecological patterns and processes longitudinally (upstream-downstream), laterally (channel-riparian-floodplain), vertically (surface water-groundwater), and temporally across local and landscape scales. However, perennial rivers are longitudinally continuous while IRES are longitudinally discontinuous. Whereas perennial rivers have bidirectional lateral connections between aquatic and terrestrial ecosystems, in IRES, this connection is unidirectional for much of the time, from terrestrial-to-aquatic only. Vertical connectivity between surface and subsurface water occurs bidirectionally and is temporally consistent in perennial rivers. However, in IRES, this exchange is temporally variable, and can become unidirectional during drying or rewetting phases. Finally, drying adds another dimension of flow variation to be considered across temporal and spatial scales in IRES, much as flooding is considered as a temporally and spatially dynamic process in perennial rivers. Here, we focus on ways in which existing models could be modified to accommodate drying as a fundamental process that can alter these patterns and processes across spatial and temporal dimensions in streams. This perspective is needed to support river science and management in our era of rapid global change, including increasing duration, frequency, and occurrence of drying.
2025-10-28T12:16:07Z
Allen, Daniel C. Datry, Thibault Boersma, Kate S. Bogan, Michael T. Boulton, Andrew J. Bruno, Daniel Busch, Michelle H. Costigan, Katie H. Dodds, Walter K. Fritz, Ken M. Godsey, Sarah E. Jones, Jeremy B. Kaletova, Tatiana Kampf, Stephanie K. Mims, Meryl C. Neeson, Thomas M. Olden, Julian D. Pastor, Amandine V Poff, N. LeRoy Ruddell, Benjamin L. Ruhi, Albert Singer, Gabriel Vezza, Paolo Ward, Adam S. Zimmer, Margaret
GUEST EDITORIAL—SPECIAL ISSUE: Mapping and modelling soil erosion to address societal challenges in a changing world
Special issue Mapping and Modelling Soil Erosion to Address Societal Challenges in a Changing World presents advances in interdisciplinary methodologies for the study of the soil erosion/land management/climate change nexus, with a focus on societal challenges linked to land degradation. Contribution of 22 research teams active in 17 countries all over the world provided a global perspective on how soil erosion research contributes to meet societal challenges of our time. The authors conclude that (a) inclusive representation of non-linear system feedback between erosion and land management; (b) combination of mapping, measuring, monitoring, and modelling methods on different temporal and spatial scales; and (c) inclusive, cooperative interdisciplinary research approaches are inevitable to support management aiming for land degradation neutrality.
2025-10-28T12:16:07Z
Smetanová, Anna Nunes, João Pedro Symeonakis, Elias Brevik, Eric Schindelwolf, Marcus Ciampalini, Rossano
Power line routing and configuration as major drivers of collision risk in two bustard species
Collision with power lines is a major cause of mortality for many bird species. Understanding the biotic and abiotic factors that increase collision risk is therefore important for implementing mitigation measures to minimize mortality, such as power line rerouting or wire marking. Here, we used collision events registered during 2003–2015 along 280 km of transmission power lines in southern Portugal to analyse spatio-temporal patterns and collision risk factors in two sympatric, threatened, and collision-prone species: the great bustard Otis tarda and the little bustard Tetrax tetrax. The occurrence of collisions was not uniform across space and time, and variations could be explained by the species' ecological requirements, distribution patterns and behaviour. Although both species fly considerable distances between areas of suitable habitat, collisions were far more likely in power line sections with > 20% (for the little bustard) or > 50% (for the great bustard) of open farmland habitat in the surroundings. Power line configuration was also important: taller pylons and those with a higher number of wire levels posed a higher risk for both species. Wire marking had a small but significant effect for the little bustard, reducing collisions risk. There was, however, no similar effect for the great bustard, possibly a result of limited data. Mitigation measures should be implemented to prevent bustard collisions, including adequate route planning, ideally avoiding areas with > 20% of open habitat. Line configuration and wire marking are particularly important where such localities cannot be avoided and power lines cross areas with a high proportion of bustard habitat, including outside protected areas.
2025-10-28T12:21:14Z
Marques, Ana Teresa Martins, Ricardo C. Silva, João Paulo M. Palmeirim, Jorge Moreira, Francisco
Fundamental research questions in subterranean biology
Five decades ago, a landmark paper in Science titled The Cave Environment heralded caves as ideal natural experimental laboratories in which to develop and address general questions in geology, ecology, biogeography, and evolutionary biology. Although the ‘caves as laboratory’ paradigm has since been advocated by subterranean biologists, there are few examples of studies that successfully translated their results into general principles. The contemporary era of big data, modelling tools, and revolutionary advances in genetics and (meta)genomics provides an opportunity to revisit unresolved questions and challenges, as well as examine promising new avenues of research in subterranean biology. Accordingly, we have developed a roadmap to guide future research endeavours in subterranean biology by adapting a well-established methodology of ‘horizon scanning’ to identify the highest priority research questions across six subject areas. Based on the expert opinion of 30 scientists from around the globe with complementary expertise and of different academic ages, we assembled an initial list of 258 fundamental questions concentrating on macroecology and microbial ecology, adaptation, evolution, and conservation. Subsequently, through online surveys, 130 subterranean biologists with various backgrounds assisted us in reducing our list to 50 top-priority questions. These research questions are broad in scope and ready to be addressed in the next decade. We believe this exercise will stimulate research towards a deeper understanding of subterranean biology and foster hypothesis-driven studies likely to resonate broadly from the traditional boundaries of this field.
2025-10-28T12:19:40Z
Mammola, Stefano Amorim, Isabel R. Bichuette, Maria E. Borges, P.A.V. Cheeptham, Naowarat Cooper, Steven J. B. Culver, David C. Deharveng, Louis Eme, David Ferreira, Rodrigo Lopes Fišer, Cene Fišer, Žiga Fong, Daniel W. Griebler, Christian Jeffery, William R. Jugovic, Jure Kowalko, Johanna E. Lilley, Thomas M. Malard, Florian Manenti, Raoul Martínez, Alejandro Meierhofer, Melissa B. Niemiller, Matthew L. Northup, Diana E. Pellegrini, Thais G. Pipan, Tanja Protas, Meredith Sofia Reboleira, Ana Venarsky, Michael P. Wynne, J. Judson Zagmajster, Maja Cardoso, Pedro
Multiple founder events explain the genetic diversity and structure of the model allopolyploid grass Brachypodium hybridum in the Iberian Peninsula hotspot
Background and Aims It is accepted that contemporary allopolyploid species have originated recurrently, but very few cases have been documented using multiple natural formations of the same species. To extend our knowledge, we have investigated the multiple origins, genetic variation and structure of the allotetraploid grass Brachypodium hybridum with respect to its progenitor diploid species B. distachyon (D genome) and B. stacei (S genome). For this, our primary focus is the Iberian Peninsula, an evolutionary hotspot for the genus Brachypodium. Methods We analysed 342 B. hybridum individuals from 36 populations using ten nuclear SSR loci and two plastid loci. The B. hybridum genetic profiles were compared with those previously reported for B. stacei and B. distachyon. In addition, phylogenetic analysis of the plastid data was performed for a reduced subset of individuals. Key Results The nuclear simple sequence repeat (SSR) genetic analysis detected medium to high genetic diversity, with a strong south-to-north genetic structure cline, and a high selfing rate in B. hybridum. Comparative genetic analysis showed a close relatedness of current B. hybridum D allelic profiles with those of B. distachyon, but a lack of similarity with those of B. stacei, suggesting another B. stacei source for the B. hybridum S alleles. Plastid analysis detected three different bidirectional allopolyploidization events: two involved distinct B. distachyon-like ancestors and one involved a B. stacei-like ancestor. The south-eastern Iberian Peninsula B. hybridum populations were more genetically diverse and could have originated from at least two hybridization events whereas north-eastern/north-western Iberian Peninsula B. hybridum populations were less diverse and may have derived from at least one hybridization event. Conclusions The genetic and evolutionary evidence supports the plausible in situ origin of the south-eastern and northern Iberian Peninsula B. hybridum allopolyploids from their respective local B. distachyon and unknown B. stacei ancestors. The untapped multiple origins and genetic variation detected in these B. hybridum populations opens the way to future evolutionary analysis of allopolyploid formation and genomic dominance and expression in the B. hybridum–B. distachyon–B. stacei grass model complex.
2025-10-28T12:26:34Z
Shiposha, Valeriia Marques, Isabel López-Alvarez, Diana Manzaneda, Antonio J Hernandez, Pilar Olonova, Marina Catalán, Pilar
Coimbra and Évora
Identity and discrepancies between the teachings of the University of Coimbra and those of the University of Évora, and their integration in the Commentary to Aristotle produced by Portuguese Jesuits known as Cursus Aristotelicus Conimbricensis.
Deep intronic mutations and human disease
Next-generation sequencing has revolutionized clinical diagnostic testing. Yet, for a substantial proportion of patients, sequence information restricted to exons and exon-intron boundaries fails to identify the genetic cause of the disease. Here we review evidence from mRNA analysis and entire genomic sequencing indicating that pathogenic mutations can occur deep within the introns of over 75 disease-associated genes. Deleterious DNA variants located more than 100 base pairs away from exon-intron junctions most commonly lead to pseudo-exon inclusion due to activation of non-canonical splice sites or changes in splicing regulatory elements. Additionally, deep intronic mutations can disrupt transcription regulatory motifs and non-coding RNA genes. This review aims to highlight the importance of studying variation in deep intronic sequence as a cause of monogenic disorders as well as hereditary cancer syndromes.
2025-10-28T12:15:10Z
Vaz-Drago, Rita Custódio, Noélia Carmo-Fonseca, Maria
Quality of Life of People with Vitiligo: A Brazilian Exploratory Study
Vitiligo is a dermatological disease characterized by the presence of hypopigmented macules on the skin. Considering that its effects are not limited to the biological dimension of the subject, it is assumed negative impacts on the quality of life of their bearers. Yet, little attention has been giving to this phenomenon in Brazilian studies. This research sought to overcome this gap by verifying the relationship between sociodemographic variables of people with Vitiligo, as well as their perceptions of discrimination and severity of the disease in their qualities of life. It is a quantitative study with a descriptive and exploratory nature, in which 200 Brazilians with Vitiligo participated, most of them female (73%), with white skin colour (50.5%) and predominantly residents of Southeast Brazil (31.02%). For data collection, a sociodemographic questionnaire and the Vitiligo-specific health-related quality of life instrument (VitiQoL) scale were used. Results revealed that female participants, with black skin colour, low income and white patches in areas of easy social perception showed worse rates of quality of life. The findings are discussed with pertinent literature, and it is expected that they contribute to the development of public policies aiming to improve the quality of life of Brazilians with Vitiligo.
2025-10-28T12:08:55Z
Do Bú, Emerson Araújo Alexandre, Maria Edna Silva De Santos, Vitória Medeiros Dos
Tectonics of the Gulf of Cadiz : the role of the Gibraltar Arc in the reactivation of the SW Iberia Margin
The process of spontaneous subduction initiation at passive margins plays a central role in the plate tectonics theory, in particular in the Wilson Cycle paradigmatic concept, which states that oceans form, evolve and finally close. The Wilson Cycle requires that after a certain time of oceanic drifting passive margins are reactivated and subduction initiates. However, the process of transformation of passive continental margins into active continental margins with subduction zones is still far from understood, and spontaneous transition examples between these two types of margins are not known. In addition, recent works based on theoretical calculations and physical modeling showed that it is mechanically unfeasible to form a new subduction system in isolation from an already existing one, i.e. spontaneous subduction initiation. One way to solve this problem is to consider that subduction initiation may generally be induced by the proximity of another subduction zone or by stress transference from a nearby collision belt, i.e. induced subduction initiation. Therefore, passive margins in the proximity of pre-existing subduction zones would represent preferential sites for the formation of new subduction zones. In this work, the Gibraltar Arc and the Southwest Iberia Margin are used as case studies to investigate the role that the orogenic arcs may have in the formation of new subduction systems at passive margins. The Atlantic margins are generally described as the typical case of passive margins, often termed Atlantic type margins. However, there are at least two regions where the Atlantic oceanic lithosphere is being consumed in subduction zones: in the Scotia and in the Lesser Antilles arcs (in the Southwestern and central West Atlantic, respectively). These subduction zones seem to have been transferred from the Eastern Pacific ocean to the Atlantic domain and potentially represent precursors to a system of convergent zones that might ultimately result in the closure of the Atlantic Ocean. However, in these two systems the oceanic lithosphere has been subducted since at least the Early Cenozoic, without lateral propagation of the subduction zones along the adjacent Atlantic passive margins. The Gulf of Cadiz, i.e. the foreland of the Gibraltar orogenic arc, has been proposed as a potential locus for a subduction zone to propagate into the open Atlantic. On the other hand, the proximity of the Gibraltar collision belt to the Southwest Iberia Margin, together with the existing overall convergence between II Africa and Iberia, induces compressive stresses that, in association with the existence of more than 100 km long active thrusts (e.g. Horseshoe Fault and Gorringe Bank), make this margin a strong candidate for the nucleation of a new subduction zone. In order to better evaluate the post-Miocene tectonics and the main tectonic driving mechanism operating in the Gulf of Cadiz an up-to-date tectonic map of this area was produced. This map was based on the coupled analysis of a multi-survey MCS dataset and the recently compiled high resolution bathymetry dataset (the SWIM bathymetry). The mapping revealed the existence of three main systems of tectonic structures: i) the subduction-related Gulf of Cadiz Accretionary Wedge (CGAW); ii) a set of WNW-ESE striking dextral strike-slip faults (the SWIM fault system); and iii) a group of NE-SW striking northwest-directed thrusts located in the Southwest Iberia Margin (the NE-SW thrust system). The subduction-related accretionary wedge (GCAW) is materialized on the seafloor by a west dipping U-shaped surface and consists in an eastward thickening pile of westwards thrusted sediments. There are evidences that this thrust wedge is active and propagating westward. The SWIM fault system is a group of WNW-ESE striking subvertical strike-slip faults extending from the eastern part of the Gulf of Cadiz, i.e. the northwest Moroccan shelf, to the Horseshoe Abyssal Plain. These faults were interpreted in this work as the Present day dextral reactivation of the old Mesozoic Tethyan plate boundary. The NE-SW striking thrust system is a group northwest directed thrusts located along the Southwest Iberia Margin, comprising the Horseshoe fault, the Marquês de Pombal fault, the Tagus Abyssal Plain fault and the Gorringe northern thrust. This NESW thrust system seems to be the result of the migration of the deformation, in the Pliocene-Quaternary, from the realm of the Gibraltar wedge to the west (onto the Horseshoe fault region) and to the north along the West Portuguese Margin. These structures may be the expression of a new compressive deformation front. Besides these three tectonic systems, other important structures were also promptly recognized such as the ENE-WSW to E-W striking system of thrusts (e.g. the Portimão pop-up and the Coral Patch Ridge), related with the overall Cenozoic NubiaIII Iberia N-S convergence, and NE-SW striking Cadiz fault, a dextral strike-slip fault that probably accommodates part the westward movement of the Gibraltar Arc. The analysis of the multibeam bathymetry data from the northwestern part of the Gulf of Cadiz also revealed the existence of several intriguing kilometric crescentic depressions lying at depths between -4300 m and -4700 m, never before reported to occur at such great depths in the scientific literature. These features are located in the Horseshoe Valley between two major tectonic structures: the GCAW and the Horseshoe fault. Morphological parameterization of these features, coupled with detailed analysis of multi-channel and middle resolution seismic profiles, showed that these crescentshaped features were formed due to the existence of specific interaction between: a) regional active thrusts on top of which most crescentic depressions are carved; and b) tectonically induced scouring comprising localized erosion and simultaneous progradational sedimentation, produced by downslope turbiditic currents. The obtained results also suggest a possible contribution of fluid migration and extrusion processes, such as mud volcanism and associated pockmark formation, besides gravity driven landslides and slumping, in the development of the studied crescentic depressions. The active (mainly blind) thrusts in which the crescentic depressions are carved root in the GCAW décollement layer, to the west of the GCAW deformation front. Therefore, the crescentic depressions are interpreted as the morphological expression of the westward propagation of the deformation related with the GCAW, into the Horseshoe Valley domain. Besides the new produced cartography of the Gulf of Cadiz, the present work also benefited from the instrumental use of analog modeling experiments. Three main different modes of tectonic interference between the SWIM strike-slip fault system (related with the overall Nubia-Iberia convergence) and the GCAW (related with the Gibraltar subduction) were tested through analog sand-box modeling, namely: a) An active accretionary wedge on top of a pre-existent inactive basement fault; b) An active strike-slip fault cutting a previously formed, inactive, accretionary wedge; and c) Simultaneous activity of both the accretionary wedge and the strike-slip fault. The results obtained and the comparison with the natural deformation pattern favor a tectonic evolution comprising two main steps: i) the development of the Gulf of Cadiz Accretionary Wedge on top of inactive, Tethyan-related, basement faults (Middle Miocene to ~1.8 Ma); ii) subsequent reactivation of these basement faults with dextral IV strike-slip motion (~1.8 Ma to Present) simultaneously with continued tectonic accretion in the GCAW. These results exclude the possibility of ongoing active SWIM wrench system cross-cutting an inactive GCAW structure. The results also support a new interpretation of the SWIM wrench system as fundamentally resulting from strikeslip reactivation of an old (Tethyan-related) plate boundary. Detail mapping in the Horseshoe Abyssal Plain also revealed the existence of a new morphotectonic pattern near the intersection (corner zone) of the SWIM 1 fault and the Horseshoe fault. Based on combined analog and numerical experiments this pattern was interpreted as resulting from the (wrench-thrust) tectonic interference between two of the main tectonic systems recognized in the Gulf of Cadiz area: the SWIM faults and the NE-SW thrusts. Finally, the results presented in this work favor a hypothetic scenario in which the Gibraltar subduction is active, but decreasing in activity since the Miocene, at the same time that an incipient subduction zone may be nucleating in the Southwest Iberia Margin. The Gulf of Cadiz may be thus seen as a place where the proximity of a preexistent subduction system could be inducing the formation of a new subduction zone in the Atlantic.
Tissue-specific splicing factor gene expression signatures
The alternative splicing code that controls and coordinates the transcriptome in complex multicellular organisms remains poorly understood. It has long been argued that regulation of alternative splicing relies on combinatorial interactions between multiple proteins, and that tissue-specific splicing decisions most likely result from differences in the concentration and/or activity of these proteins. However, large-scale data to systematically address this issue have just recently started to become available. Here we show that splicing factor gene expression signatures can be identified that reflect cell type and tissue-specific patterns of alternative splicing. We used a computational approach to analyze microarray-based gene expression profiles of splicing factors from mouse, chimpanzee and human tissues. Our results show that brain and testis, the two tissues with highest levels of alternative splicing events, have the largest number of splicing factor genes that are most highly differentially expressed. We further identified SR protein kinases and small nuclear ribonucleoprotein particle (snRNP) proteins among the splicing factor genes that are most highly differentially expressed in a particular tissue. These results indicate the power of generating signature-based predictions as an initial computational approach into a global view of tissue-specific alternative splicing regulation.
2025-10-28T12:28:20Z
Grosso, Ana Rita Gomes, Anita Q. Barbosa-Morais, Nuno Caldeira, Sandra Thorne, Natalie P. Grech, Godfrey von Lindern, Marieke Carmo-Fonseca, Maria