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Gonadal fate in mammals is determined during embryogenesis and is actively maintained in adulthood. This study shows that E3-SUMO ligase activity of TRIM28 is required for ovarian identity maintenance and testicular-specific gene repression in mouse adult ovary; in its absence, ovarian granulosa cells transdifferentiate to Sertoli cells.

This article proposes a systematic review of the recent literature on the impacts of the deployment of autonomous vehicles through the lens of lifestyle changes that will modify our mobility practices. It discusses the main findings of the studies, analyzes their links with the foresight methods used by their authors, and identifies research gaps. Four components of lifestyles are considered: residential location, car ownership, activity patterns, and tourism. Particular attention is given to the diversity of the reviewed foresight approaches, to the way they complement one another in the construction of knowledge, and to their influence on the forecasts and the lessons learned. Our work shows a convergence of results across methods, especially for expected impacts on household location and car ownership, and the influence of the way autonomous vehicles are deployed. Our analysis also makes it possible to draw up a more comprehensive and nuanced picture of the anticipated changes in lifestyles, and the main sources of uncertainty. Finally, our work identifies several research gaps and avenues for future studies such as the impacts on job choices and tourism, the need for a better understanding of the links between the different deployment models for autonomous vehicles, and the need to explore more scenarios that are compatible with environmentally- and socially-oriented goals.

Abstract Background Perioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen is considered as the new standard chemotherapy regimen for perioperative strategy, despite associated with a 5-year overall survival rate (OS) amounting 45% following radical surgery. Immunotherapy with antibodies that inhibit PD-1/ PD-L1 interaction has recently emerged as a new treatment option with promising and encouraging early trial results for patients with advanced or metastatic gastric or GEJ adenocarcinoma. Currently, no trials have investigated the impact of perioperative immunotherapy in combination with chemotherapy for resectable gastric or GEJ adenocarcinoma. Methods GASPAR trial is a multicenter open-label, nonrandomized, phase II trial to evaluate the efficacy and safety of Spartalizumab in combination with the FLOT regimen as perioperative treatment for resectable gastric or GEJ adenocarcinoma. The main endpoint is the proportion of patients with pathological complete regression (pCR) in the primary tumour after preoperative treatment. Systemic treatment will include a pre-operative neoadjuvant and a post-operative adjuvant treatment, during which FLOT regimen will be administered every two weeks for 4 cycles and Spartalizumab every four weeks for 2 cycles. For patients with confirmed tumor resectability on imaging assessment, surgery will be realized within 4–6 weeks after the last dose of preoperative chemotherapy. Post-operative systemic treatment will then be initiated within 4–10 weeks after surgery. Using a Simon’s two-stage design, up to 67 patients will be enrolled, including 23 in the first stage. Discussion Currently, no trials have investigated the impact of immunotherapy in combination with FLOT chemotherapy as perioperative treatment for resectable gastric or GEJ adenocarcinoma. Some studies have suggested a change in the tumor immune micro-environment following neoadjuvant chemotherapy in this setting, reinforcing the relevance to propose a phase II trial evaluating efficacy and safety of Spartalizumab in combination with perioperative chemotherapy, with the aim of improving treatment efficacy and survival outcomes. Trial registration NCT04736485, registered February, 3, 2021.

A net zero transition is likely to generate substantial and irreversible economic transformation. High-carbon industries and their related occupations will disappear, while new low-carbon industries and occupations will be created. In the aggregate, the impact of the transition on GDP and employment is commonly projected to be relatively moderate. However, such estimates hide drastic distributional issues that are sectorally and regionally concentrated. We use three sectorally detailed and regionally disaggregated macroeconomic models to explore the possible levels and impacts of structural change in a well below 2°C scenario. In addition to the expected decline in the carbon-intensive industries, we observe secondary impacts, particularly in the services sectors, that vary significantly between models. The risks entailed with structural change involve worsening economic disparity and societal division that could exacerbate existing socioeconomic and political polarisation. Impact assessments of decarbonisation should consider such distributional issues to avoid post-industrial decline and widening socioeconomic inequalities. [ABSTRACT FROM AUTHOR]

We study the impact of socioeconomic factors on two key parameters of epidemic dynamics. Specifically, we investigate a parameter capturing the rate of deceleration at the very start of an epidemic, and a parameter that reflects the pre-peak and post-peak dynamics at the turning point of an epidemic like coronavirus disease 2019 (COVID-19). We find two important results. The policies to fight COVID-19 (such as social distancing and containment) have been effective in reducing the overall number of new infections, because they influence not only the epidemic peaks, but also the speed of spread of the disease in its early stages. The second important result of our research concerns the role of healthcare infrastructure. They are just as effective as anti-COVID policies, not only in preventing an epidemic from spreading too quickly at the outset, but also in creating the desired dynamic around peaks: slow spreading, then rapid disappearance. [ABSTRACT FROM AUTHOR]

Aquaculture has been recognised for achieving multiple United Nations Sustainable Development Goals; its further growth depends on understanding, and responding to, societal perceptions in a broader context. Thus, this study aims to understand societal perceptions of aquaculture through a scoping review and media analysis. A scoping review identified 151 academic studies for inclusion in our five identified research clusters: (1) social acceptability, (2) growth and development, (3) media coverage, (4) sustainable aquaculture, and (5) consumer perceptions. Further, newspaper articles (n = 100) were sampled from the United Kingdom, Denmark, France, Spain, Turkey, and China; elsewhere all articles identified were included (Poland, 79; Hungary, 29; India, 70). The findings suggest that scientific and newspaper articles tend to present sustainability aspects in a simplified form. Key stakeholder groups include fish farming enterprises, civil society, governmental officials, scientists, and business leaders both within aquaculture value chains (retailers/wholesalers, technology industry) and outside of them (fisheries, tourism). Also, other stakeholders included the public (indigenous groups, residents, consumers). The stakeholder groups perceived aquaculture differently and depending on the circumstances and context, their perceptions ranged from positive to negative. Many factors influenced their perceptions, including aquaculture's impact on multiple sustainability dimensions, knowledge, transparency, personal interests, types, and location of aquaculture practises, regulations, experience, and sociodemographic characteristics such as age, gender, education, and income. We recommend that aquaculture practitioners focus on context‐specific multifaceted strategies—prioritising transparency, communication, and accountability—and provide essential knowledge to ensure that societal perceptions of aquaculture are based on accurate, empirical information. [ABSTRACT FROM AUTHOR]

Global Integrated Assessment Models (IAMs) used to characterise mitigation pathways have very limited or no formal representation of lifestyles and lifestyle change. We demonstrate a novel approach to endogenously simulating low-carbon lifestyle heterogeneity and lifestyle change through soft-coupling with our new empirically-based LIFE model. Coupling LIFE to global IAMs enables dynamic simulation of distinctive lifestyle change contributions to targeted mitigation strategies. We set out the empirical basis of the LIFE model, the methodological steps for soft-coupling to a global IAM, and show results from a test application to the residential sector using the MESSAGEix-Buildings model. A first key insight is that coupling with the LIFE model introduces heterogeneous behaviour between ‘engaged’ types, who experience faster and higher reductions in final energy demand compared to ‘disengaged’ types. When we further simulate a widespread shift in normative values, this gap is closed. A second key insight is that drivers of lifestyle change, act differently across ‘Improve’ and ‘Avoid’ dimensions. The ‘disengaged’ types, characterised by lower incomes, are more highly responsive to energy saving ‘Avoid’ behaviours. Our approach demonstrates how improved understanding of lifestyle change dynamics and more realistic, empirically-based quantitative simulations in climate mitigation pathways enriches scientific and policy analysis of how to achieve Paris Climate Agreement goals.

Marine and coastal activities are closely interrelated, and conflicts among different sectors can undermine management and conservation objectives. Governance systems for fisheries, power generation, irrigation, aquaculture, marine biodiversity conservation, and other coastal and maritime activities are typically organized to manage conflicts within sectors, rather than across them. Based on the discussions around eight case studies presented at a workshop held in Brest in June 2019, this paper explores institutional approaches to move beyond managing conflicts within a sector. We primarily focus on cases where the groups and sectors involved are heterogeneous in terms of: the jurisdiction they fall under; their objectives; and the way they value ecosystem services. The paper first presents a synthesis of frameworks for understanding and managing cross-sectoral governance conflicts, drawing from social and natural sciences. We highlight commonalities but also conceptual differences across disciplines to address these issues. We then propose a novel analytical framework which we used to evaluate the eight case studies. Based on the main lessons learned from case studies, we then discuss the feasibility and key determinants of stakeholder collaboration as well as compensation and incentive schemes. The discussion concludes with future research needs to support policy development and inform integrated institutional regimes that consider the diversity of stakeholder interests and the potential benefits of cross-sectoral coordination.

Integrated assessment models (IAMs) have emerged as key tools for building and assessing long term climate mitigation scenarios. Due to their central role in the recent IPCC assessments, and international climate policy analyses more generally, and the high uncertainties related to future projections, IAMs have been critically assessed by scholars from different fields receiving various critiques ranging from adequacy of their methods to how their results are used and communicated. Although IAMs are conceptually diverse and evolved in very different directions, they tend to be criticised under the umbrella of ‘IAMs’. Here we first briefly summarise the IAM landscape and how models differ from each other. We then proceed to discuss six prominent critiques emerging from the recent literature, reflect and respond to them in the light of IAM diversity and ongoing work and suggest ways forward. The six critiques relate to (a) representation of heterogeneous actors in the models, (b) modelling of technology diffusion and dynamics, (c) representation of capital markets, (d) energy-economy feedbacks, (e) policy scenarios, and (f) interpretation and use of model results.

Lifestyle changes are key factors of the climate mitigation challenge because they drive the demand for energy, goods and food. They have received growing attention in the development and assessment of mitigation pathways, one of the key approaches used to inform mitigation policies. This paper contributes to this emerging literature by examining the political and scientific implications of integrating lifestyle changes into mitigation pathways. We analyse a large sample of pathways, supplemented by interviews with practitioners, to provide a perspective relevant to both scenario production practices themselves and the science-policy process in which they are included. We use three illustrative pathways to describe what it means to explore lifestyle changes and how this exploration can be conducted (indicators, dimensions, precision). We summarize the observed benefits of the explorations of lifestyle changes in scenario production by considering three main contributions of scenarios to policy decision-making: explicit knowledge, mediation tools and framing power. We also discuss why the integration of lifestyle changes poses a potential challenge to the robustness and reliability of pathway production methodologies, which is a condition for their policy-relevance. We therefore argue that the implications of this integration need to be carefully characterized in order to maximize the policy relevance of the analysis without compromising the robustness of the scenario development and assessment process. The nature of lifestyles, which reflect values and preferences and require a multidisciplinary approach, raises significant policy neutrality challenges and scientific challenges. Overcoming these challenges can lead to more policy-relevant pathways: we describe existing approaches in the literature and analyse their contributions and limitations.

The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2) addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation.

Symbionts are widespread among eukaryotes and their impacts on the ecology and evolution of their hosts are meaningful. Most insects harbour obligate and facultative symbiotic bacteria that can influence their phenotype. In the pea aphid Acyrthosiphon pisum, an astounding symbiotic-mediated phenotype has been recently observed: when infected with the symbiotic bacteria Rickettsiella viridis, young red aphid larvae become greener at adulthood and even darker green when co-infected with Rickettsiella viridis and Hamiltonella defensa. As body colour affects the susceptibility towards natural enemies in aphids, the influence of the colour change due to these facultative symbionts on the host survival in presence of predators was tested. Our results suggested that the Rickettsiella viridis infection may impact positively host survival by reducing predation risk. Due to results from uninfected aphids (i.e., more green ones attacked), the main assumption is that this symbiotic infection would deter the predatory ladybird feeding by reducing the profitability of their hosts rather than decreasing host detection through body colour change. Aphids co-infected with Rickettsiella viridis and Hamiltonella defensa were, however, more exposed to predation suggesting an ecological cost associated with multiple infections. The underlying mechanisms and ecological consequences of these symbiotic effects are discussed.

After Chernobyl and Fukushima Daï Chi, two major nuclear accidents, large amounts of radionuclides were released in the environment, mostly caesium 137 (137Cs). Populations living in contaminated territories are chronically exposed to radionuclides by ingestion of contaminated food. However, questions still remain regarding the effects of low dose ionizing radiation exposure on the development and progression of cardiovascular diseases. We therefore investigated the effects of a chronic internal exposure to 137Cs on atherosclerosis in predisposed ApoE-/- mice. Mice were exposed daily to 0, 4, 20 or 100 kBq/l 137Cs in drinking water, corresponding to range of concentrations found in contaminated territories, for 6 or 9 months. We evaluated plaque size and phenotype, inflammatory profile, and oxidative stress status in different experimental groups. Results did not show any differences in atherosclerosis progression between mice exposed to 137Cs and unexposed controls. However, 137Cs exposed mice developed more stable plaques with decreased macrophage content, associated with reduced aortic expression of pro-inflammatory factors (CRP, TNFα, MCP-1, IFNγ) and adhesion molecules (ICAM-1, VCAM-1 and E-selectin). Lesions of mice exposed to 137Cs were also characterized by enhanced collagen and smooth muscle cell content, concurrent with reduced matrix metalloproteinase MMP8 and MMP13 expression. These results suggest that low dose chronic exposure of 137Cs in ApoE-/- mice enhances atherosclerotic lesion stability by inhibiting pro-inflammatory cytokine and MMP production, resulting in collagen-rich plaques with greater smooth muscle cell and less macrophage content.