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- The polyglutamine protein ATXN2: from its molecular functions to its involvement in diseasePublication . Costa, Rafael Gomes da; Vieira da Conceição, André Filipe; Albuquerque Andrade de Matos, Carlos Adriano; Nóbrega, ClévioA CAG repeat sequence in the ATXN2 gene encodes a polyglutamine (polyQ) tract within the ataxin-2 (ATXN2) protein, showcasing a complex landscape of functions that have been progressively unveiled over recent decades. Despite significant progresses in the field, a comprehensive overview of the mechanisms governed by ATXN2 remains elusive. This multifaceted protein emerges as a key player in RNA metabolism, stress granules dynamics, endocytosis, calcium signaling, and the regulation of the circadian rhythm. The CAG overexpansion within the ATXN2 gene produces a protein with an extended poly(Q) tract, inducing consequential alterations in conformational dynamics which confer a toxic gain and/or partial loss of function. Although overexpanded ATXN2 is predominantly linked to spinocerebellar ataxia type 2 (SCA2), intermediate expansions are also implicated in amyotrophic lateral sclerosis (ALS) and parkinsonism. While the molecular intricacies await full elucidation, SCA2 presents ATXN2-associated pathological features, encompassing autophagy impairment, RNA-mediated toxicity, heightened oxidative stress, and disruption of calcium homeostasis. Presently, SCA2 remains incurable, with patients reliant on symptomatic and supportive treatments. In the pursuit of therapeutic solutions, various studies have explored avenues ranging from pharmacological drugs to advanced therapies, including cell or gene-based approaches. These endeavours aim to address the root causes or counteract distinct pathological features of SCA2. This review is intended to provide an updated compendium of ATXN2 functions, delineate the associated pathological mechanisms, and present current perspectives on the development of innovative therapeutic strategies.
- New insights into the eastern subpolar North Atlantic meridional overturning circulation from OVIDEPublication . Mercier, Herlé; Desbruyères, Damien; Lherminier, Pascale; Velo, Antón; Carracedo, Lidia; F. Pérez, Fiz; Morente Fontela, MarcosThe Atlantic Meridional Overturning Circulation (AMOC) is a key component of the Earth's climate. However, there are few long time series of observations of the AMOC, and the study of the mechanisms driving its variability depends mainly on numerical simulations. Here, we use four ocean circulation estimates produced by different data-driven approaches of increasing complexity to analyse the seasonal to decadal variability of the subpolar AMOC across the Greenland-Portugal OVIDE (Observatoire de la Variabilit & eacute; Interannuelle & agrave; D & Eacute;cennale) line since 1993. We decompose the MOC strength variability into a velocity-driven component due to circulation changes and a volume-driven component due to changes in the depth of the overturning maximum isopycnal. We show that the variance of the time series is dominated by seasonal variability, which is due to both seasonal variability in the volume of the AMOC limbs (linked to the seasonal cycle of density in the East Greenland Current) and to seasonal variability in the transport of the Eastern Boundary Current. The decadal variability of the subpolar AMOC is mainly caused by changes in velocity, which after the mid-2000s are partly offset by changes in the volume of the AMOC limbs.
- Up to 80% of threatened and commercial species across European marine protected areas face novel climates under high emission scenarioPublication . Predragovic, Milica; Assis, Jorge; Sumaila, U. Rashid; Gonçalves, Jorge Manuel Santos; Cvitanovic, Christopher; Horta e Costa, BarbaraMarine protected areas (MPAs) are a critical tool for safeguarding marine species and habitats for the future, though the effects of projected climate change raise concerns about their long-term success. Assessing the degree to which MPAs may be exposed to future novel climatic conditions is, therefore, crucial for informing conservation and management actions aimed at ensuring a resilient and thriving ocean in the years to come. Here, we evaluate the future exposure of 398 threatened and commercially important species to novel and extremely novel climatic conditions within European MPAs. We estimated climate novelty through multivariate analyses considering biologically meaningful distribution drivers of temperature, oxygen, pH, and primary productivity from present-day to the end of the 21st-century conditions under contrasting shared socioeconomic pathways (SSP) scenarios—low emission scenario (SSP1–1.9) and high emission scenario (SSP5–8.5). Our findings suggest that, under SSP1–1.9, ~6.5% of species and 0.5% of European MPAs will be at risk due to future novel conditions. In contrast, under SSP5–8.5, 87% of MPAs and 80% of species are projected to be at risk. Notably, up to 100% of species currently located in the MPAs of enclosed and semi-enclosed seas like the Baltic Sea and the Black Sea are projected to be exposed to novel or even extremely novel conditions. Virtually all species in most of those regions will be at risk, suggesting that even new MPAs might not be able to adequately protect them. Comparatively, the Norwegian Sea, North-East Atlantic, and western parts of the Mediterranean and North Seas are expected to be less impacted even under the high emission scenario. Overall, our study advances the understanding of the potential impacts of future climate change scenarios on threatened and commercially important marine species in European MPAs and reinforces the urgent need to meet the Paris Agreement. Our results suggest that existing approaches to marine governance in Europe may be insufficient for ensuring the success of MPAs in light of future impacts and that novel anticipatory forms of governance are needed.