Arctic photoautotrophic communities must survive through polar night darkness until light returns in spring. We tracked changes in the cellular resource allocations and functional capacities of a ...polar sea‐ice diatom, Fragilariopsis cylindrus, to understand acclimation processes in both darkness and during the subsequent return to light. We measured parameters at specific time‐points over 3 months of darkness, and then over 6 d after a return to light. Measured parameters included cell number and size, cellular carbon and nitrogen quotas, lipid and pigment contents, concentration of key proteins of the photosynthetic system, photosynthetic parameters based on both variable fluorescence and carbon assimilation, and the level of nonphotochemical quenching. A stable functional state was reached within a few days after the transition to dark and was then maintained throughout 3 months of darkness. The dark period resulted in a decrease of lipid droplet cell quota (−6%), chlorophyll a cell quota (−41%) and the maximum carbon fixation rate per cell (−98%). Return to light after 1.5 months of darkness resulted in a strong induction of nonphotochemical quenching of excitation and a fast recovery of the maximum carbon fixation rate within 1 d, followed by a rapid increase in the cell number. Return to light after 3 months of darkness showed an increase of mortality or a profound downregulation induced over longer periods of darkness.
The Paris Climate Agreements and Sustainable Development Goals, signed by 197 countries, present agendas and address key issues for implementing multi-scale responses for sustainable development ...under climate change—an effort that must involve local, regional, national, and supra-national stakeholders. In that regard, Continental Carbon Sequestration (CoCS) and conservation of carbon sinks are recognized increasingly as having potentially important roles in mitigating climate change and adapting to it. Making that potential a reality will require indicators of success for various stakeholders from multidisciplinary backgrounds, plus promotion of long-term implementation of strategic action towards civil society (e.g., law and policy makers, economists, and farmers). To help meet those challenges, this discussion paper summarizes the state of the art and uncertainties regarding CoCS, taking an interdisciplinary, holistic approach toward understanding these complex issues. The first part of the paper discusses the carbon cycle’s bio-geophysical processes, while the second introduces the plurality of geographical scales to be addressed when dealing with landscape management for CoCS. The third part addresses systemic viability, vulnerability, and resilience in CoCS practices, before concluding with the need to develop inter-disciplinarity in sustainable science, participative research, and the societal implications of sustainable CoCS actions.
RIP1 kinase regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including inflammatory and neurological diseases. Currently, RIP1 ...kinase inhibitors have advanced into early clinical trials for evaluation in inflammatory diseases such as psoriasis, rheumatoid arthritis, and ulcerative colitis and neurological diseases such as amyotrophic lateral sclerosis and Alzheimer’s disease. In this paper, we report on the design of potent and highly selective dihydropyrazole (DHP) RIP1 kinase inhibitors starting from a high-throughput screen and the lead-optimization of this series from a lead with minimal rat oral exposure to the identification of dihydropyrazole 77 with good pharmacokinetic profiles in multiple species. Additionally, we identified a potent murine RIP1 kinase inhibitor 76 as a valuable in vivo tool molecule suitable for evaluating the role of RIP1 kinase in chronic models of disease. DHP 76 showed efficacy in mouse models of both multiple sclerosis and human retinitis pigmentosa.
Regional analyses assessing the vulnerabilities of forest ecosystems and the forest sector to climate change are key to considering the heterogeneity of climate change impacts as well as the fact ...that risks, opportunities, and adaptation capacities might differ regionally. Here we provide the Regional Integrated Assessment of climate change on Quebec's forests, a work that involved several research teams and focused on climate change impacts on Quebec's commercial forests and on potential adaptation solutions. Our work showed that climate change will alter several ecological processes within Quebec's forests. These changes will result in important modifications in forest landscapes. Harvest will cumulate with climate change effects to further alter future forest landscapes, which will also have consequences on wildlife habitats (including woodland caribou habitat), avian biodiversity, carbon budget, and a variety of forest landscape values for Indigenous peoples. The adaptation of the forest sector will be crucial to mitigate the impacts of climate change on forest ecosystem goods and services and improve their resilience. Moving forward, a broad range of adaptation measures, notably through reducing harvest levels, should be explored to help strike a balance among social, ecological, and economic values. We conclude that without climate adaptation, strong negative economic and ecological impacts will likely affect Quebec's forests.
Avec l’attrait engendré par les avancées en informatique et en intelligence artificielle, les personnages virtuels (c.-à-d. personnages représentés numériquement d’apparence humaine ou non) sont ...pressentis comme de futurs prestataires de soins en santé mentale. À ce jour, l’utilisation principale de tels personnages est toutefois marginale et se limite à une aide complémentaire à la pratique des cliniciens. Des préoccupations liées à la sécurité et l’efficacité, ainsi qu’un manque de connaissances et de compétences peuvent expliquer cette discordance entre ce que certains s’imaginent être l’utilisation future (voire futuriste) des personnages virtuels et leur utilisation actuelle. Un aperçu des récentes données probantes contribuerait à réduire cette divergence et à mieux saisir les enjeux associés à leur utilisation plus répandue en santé mentale.
Objectif Cet article vise à informer tous les acteurs impliqués, dont les cliniciens, quant au potentiel des personnages virtuels en santé mentale, et de les sensibiliser aux enjeux associés à leur usage.
Méthode Une recension narrative de la littérature a été réalisée afin de synthétiser les informations obtenues de la recherche fondamentale et clinique, et de discuter des considérations sociétales.
Résultats Plusieurs caractéristiques des personnages virtuels provenant de la recherche fondamentale ont le potentiel d’influencer les interactions entre un patient et un clinicien. Elles peuvent être regroupées en deux grandes catégories : les caractéristiques liées à la perception (p. ex. réalisme) et celles liées à l’attribution spontanée d’une catégorie sociale au personnage virtuel par un observateur (p. ex. genre). Selon la recherche clinique, plusieurs interventions ou évaluations utilisant des personnages virtuels ont montré divers degrés d’efficacité en santé mentale, et certains éléments de la relation thérapeutique (p. ex. alliance et empathie) peuvent d’ailleurs être présents lors d’une relation avec un personnage virtuel. De multiples enjeux socioéconomiques et éthiques doivent aussi être discutés en vue d’un développement et d’une utilisation plus accrue qui soient responsables et éthiques. Bien que l’accessibilité et la disponibilité des personnages virtuels constituent un avantage indéniable pour l’offre de services en santé mentale, certaines iniquités demeurent. L’accumulation de données biométriques (p. ex. rythme cardiaque) a également le potentiel d’enrichir le travail des cliniciens, mais aussi de mener au développement de personnages virtuels autonomes à l’aide de l’intelligence artificielle, ce qui pourrait conduire à certains dérapages (p. ex. erreurs de décision clinique). Quelques pistes de recommandations visant à éviter ces effets indésirables sont présentées.
Conclusion L’emploi des personnages virtuels sera de plus en plus répandu en santé mentale en raison de leurs avantages prometteurs. Ainsi, il est souhaitable que tous les acteurs impliqués s’informent sur leur usage dans ce contexte, se sensibilisent aux enjeux spécifiques, participent activement aux discussions quant à leur développement et adoptent des recommandations uniformes en vue d’un usage sécuritaire et éthique en santé mentale.
We present the results of the analysis of eight years of Fermi-LAT data of the pulsar/pulsar wind nebula complex PSR J0205+6449/3C 58. Using a contemporaneous ephemeris, we carried out a detailed ...analysis of PSR J0205+6449 both during its off-peak and on-peak phase intervals. 3C 58 is significantly detected during the off-peak phase interval. We show that the spectral energy distribution at high energies is the same disregarding the phases considered, and thus that this part of the spectrum is most likely dominated by the nebula radiation. We present results of theoretical models of the nebula and the magnetospheric emission that confirm this interpretation. Possible high-energy flares from 3C 58 were searched for, but none were unambiguously identified.
Transforming growth factor (TGF)-β1 plays an essential role in cell growth and differentiation. It is also considered as a gatekeeper of immune homeostasis with gene disruption leading to autoimmune ...and inflammatory diseases. TGF-β1 is produced as an inactive precursor polypeptide that can be efficiently secreted but correct proteolytic cleavage is an essential step for its activation. Assessment of the cleavage site has revealed a unique R-H-R-R sequence reminiscent of proprotein convertase (PC) recognition motifs and has previously demonstrated that this PC-like cleavage site is correctly cleaved by furin, a member of the PC family. Here we report that among PC members, furin more closely satisfies the requirements needed to fulfill the role of a genuine TGF-β1 convertase. Even though six members of the PC family have the ability to cleave TGF-β1, ectopic expression of α
1-antitrypsin Portland (α
1-AT-PDX), a potent furin inhibitor, blocked 80% of TGF-β1 processing mediated by endogenous enzymes as demonstrated in an
in vitro digestion assay. Genetic complementation of a furin-deficient LoVo cell line with the wild-type gene restores the production of mature and bioactivable TGF-β1. Moreover, both furin and TGF-β are coordinately expressed and regulated
in vitro and
in vivo in the hematopoietic and immune system, an important tissue target. These results demonstrate for the first time that furin is an authentic and adaptive TGF-β1-converting enzyme whereas other members of the PC family might substitute or supplement furin activity. Our study advances our comprehension of the complexity of the TGF-β system and should facilitate the development of therapeutically useful TGF-β inhibitors.
The cornerstone of hemostasis is the ability of the organism to limit the enzymatic processes involved, thereby avoiding thrombosis. For this, anticoagulant systems in place involve serpins, such as ...PAI-1 and antithrombin III, which bind to their targeted serine proteases and limit their period of activity. We have previously identified the serine protease furin as a platelet-derived enzyme with an intrinsic role in platelet functions. We now report that furin enzymatic activity decreased rapidly following platelet activation, corresponding with the increase in formation of a high 180 M(r) SDS-stable complex composed of furin and the PI8 serpin. PI8 is shown to be a platelet-derived constituent, synthesized by megakaryocytes and stored in platelets prior to its release. Immunoprecipitation and purification of the PI8-furin complex confirmed their direct interaction and indicates that one of the roles of PI8 is to inhibit furin enzymatic activity. Furthermore, our findings demonstrate the inhibitory capacity of exogenous PI8 in platelet aggregation assays. The finding that PI8 is released by platelets and controls functional responses suggests a role for this serpin in platelet-regulated pathophysiological responses.
The supernova remnant (SNR) Puppis A (aka G260.4-3.4) is a middle-aged supernova remnant, which displays increasing X-ray surface brightness from West to East corresponding to an increasing density ...of the ambient interstellar medium at the Eastern and Northern shell. The dense IR photon field and the high ambient density around the remnant make it an ideal case to study in γ-rays. Gamma-ray studies based on three years of observations with the Large Area Telescope (LAT) aboard Fermi have revealed the high energy gamma-ray emission from SNR Puppis A. The γ-ray emission from the remnant is spatially extended, and nicely matches the radio and X-ray morphologies. Its γ-ray spectrum is well described by a simple power law with an index of ~2.1, and it is among the faintest supernova remnants yet detected at GeV energies. To constrain the relativistic electron population, seven years of Wilkinson Microwave Anisotropy Probe (WMAP) data were also analyzed, and enabled to extend the radio spectrum up to 93 GHz. The results obtained in the radio and γ-ray domains are described in detail, as well as the possible origins of the high energy γ-ray emission (Bremsstrahlung, Inverse Compton scattering by electrons or decay of neutral pions produced by proton interactions).
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