Glutathione limits Ero1-dependent oxidation in the endoplasmic reticulum

Many proteins of the secretory pathway contain disulfide bonds that are essential for structure and function. In the endoplasmic reticulum (ER), Ero1alpha and Ero1beta oxidize protein disulfide isomerase (PDI), which in turn transfers oxidative equivalents to newly synthesized cargo proteins. However, oxidation must be limited, as some reduced PDI is necessary for disulfide isomerization and ER-associated degradation. Here we show that in semipermeable cells, PDI is more oxidized, disulfide bonds are formed faster, and high molecular mass covalent protein aggregates accumulate in the absence of cytosol. Addition of reduced glutathione (GSH) reduces PDI and restores normal disulfide formation rates. A higher GSH concentration is needed to balance oxidative folding in semipermeable cells overexpressing Ero1alpha, indicating that cytosolic GSH and lumenal Ero1alpha play antagonistic roles in controlling the ER redox. Moreover, the overexpression of Ero1alpha significantly increases the GSH content in HeLa cells. Our data demonstrate tight connections between ER and cytosol to guarantee redox exchange across compartments: a reducing cytosol is important to ensure disulfide isomerization in secretory proteins

pysteps - a community-driven open-source library for precipitation nowcasting

Póster presentado en: 3rd European Nowcasting Conference, celebrada en la sede central de AEMET en Madrid del 24 al 26 de abril de 2019

Assessing whether artificial intelligence is an enabler or an inhibitor of sustainability at indicator level

"Since the early phase of the artificial-intelligence (AI) era expectations towards AI are high, with experts believing that AI paves the way for managing and handling various global challenges. However, the significant enabling and inhibiting influence of AI for sustainable development needs to be assessed carefully, given that the technology diffuses rapidly and affects millions of people worldwide on a day-to-day basis. To address this challenge, a panel discussion was organized by the KTH Royal Institute of Technology, the AI Sustainability Center and MIT Massachusetts Institute of Technology, gathering a wide range of AI experts. This paper summarizes the insights from the panel discussion around the following themes: The role of AI in achieving the Sustainable Development Goals (SDGs) AI for a prosperous 21st century Transparency, automated decision-making processes, and personal profiling and Measuring the relevance of Digitalization and Artificial Intelligence (D&AI) at the indicator level of SDGs. The research-backed panel discussion was dedicated to recognize and prioritize the agenda for addressing the pressing research gaps for academic research, funding bodies, professionals, as well as industry with an emphasis on the transportation sector. A common conclusion across these themes was the need to go beyond the development of AI in sectorial silos, so as to understand the impacts AI might have across societal, environmental, and economic outcomes. The recordings of the panel discussion can be found at: https://www.kth.se/en/2.18487/evenemang/the-role-of-ai-in-achieving-the-sdgs-enabler-or-inhibitor-1.1001364?date=2020â 08â 20&length=1&orglength=185&orgdate=2020â 06â 30 Short link: https://bit.ly/2Kap1tE © 2021"The authors acknowledge the KTH Sustainability Office and the KTH Digitalization Platform for their provided funding, which enabled the organization of this panel discussion. SG acknowledges the funding provided by the German Federal Ministry for Education and Research (BMBF) for the project “digitainable”. SDL acknowledges support through the Spanish Governmen

The cost of cooking a meal. The case of Nyeri County, Kenya

Energy for cooking is considered essential in achieving modern energy access. Despite this, almost three billion people worldwide still use solid fuels to meet their cooking needs. To better support practitioners and policy-makers, this paper presents a new model for comparing cooking solutions and its key output metric: the 'levelized cost of cooking a meal' (LCCM). The model is applied to compare several cooking solutions in the case study area of Nyeri County in Kenya. The cooking access targets are connected to the International Workshop Agreement and Global Tracking Framework's tiers of cooking energy access. Results show how an increased energy access with improved firewood and charcoal cookstoves could reduce both household's LCCMs and the total costs compared to traditional firewood cooking over the modelling period. On the other hand, switching to cleaner cooking solutions, such as LPG- and electricity, would result in higher costs for the end-user highlighting that this transition is not straightforward. The paper also contextualizes the results into the wider socio-economic context. It finds that a tradeoff is present between minimizing costs for households and meeting household priorities, thus maximizing the potential benefits of clean cooking without dismissing the use of biomass altogether

Connecting climate action with other sustainable development goals

The international community has committed to combat climate change and achieve 17 Sustainable Development Goals (SDGs). Here we explore (dis)connections in evidence and governance between these commitments. Our structured evidence review suggests that climate change can undermine 16 SDGs, while combatting climate change can reinforce all 17 SDGs but undermine efforts to achieve 12. Understanding these relationships requires wider and deeper interdisciplinary collaboration. Climate change and sustainable development governance should be better connected to maximize the effectiveness of action in both domains. The emergence around the world of new coordinating institutions and sustainable development planning represents promising progress

Characterization of a new trabectedin-resistant myxoid liposarcoma cell line that shows collateral sensitivity to methylating agents

Myxoid Liposarcomas (MLS), characterized by the expression of FUS-CHOP fusion gene are clinically very sensitive to the DNA binding antitumor agent, trabectedin. However, resistance eventually occurs, preventing disease eradication. To investigate the mechanisms of resistance, a trabectedin resistant cell line, 402-91/ET, was developed. The resistance to trabectedin was not related to the expression of MDR related proteins, uptake/efflux of trabectedin or GSH levels that were similar in parental and resistant cells. The 402-91/ET cells were hypersensitive to UV light because of a nucleotide excision repair defect: XPG complementation decreased sensitivity to UV rays, but only partially to trabectedin. 402-91/ET cells showed collateral sensitivity to temozolomide due to the lack of O(6) -methylguanine-DNA-methyltransferase (MGMT) activity, related to the hypermethylation of MGMT promoter. In 402-91 cells chromatin immunoprecipitation (ChIP) assays showed that FUS-CHOP was bound to the PTX3 and FN1 gene promoters, as previously described, and trabectedin caused FUS-CHOP detachment from DNA. Here we report that, in contrast, in 402-91/ET cells, FUS-CHOP was not bound to these promoters. Differences in the modulation of transcription of genes involved in different pathways including signal transduction, apoptosis and stress response between the two cell lines were found. Trabectedin activates the transcription of genes involved in the adipogenic-program such as c/EBPα and β, in 402-91 but not in 402-91/ET cell lines. The collateral sensitivity of 402-91/ET to temozolomide provides the rationale to investigate the potential use of methylating agents in MLS patients resistant to trabectedin

Targeting climate adaptation to safeguard and advance the Sustainable Development Goals

The international community has committed to achieve 169 Sustainable Development Goal (SDG) targets by 2030 and to enhance climate adaptation under the Paris Agreement. Despite the potential for synergies, aligning SDG and climate adaptation efforts is inhibited by an inadequate understanding of the complex relationship between SDG targets and adaptation to impacts of climate change. Here we propose a framework to conceptualise how ecosystems and socio-economic sectors mediate this relationship, which provides a more nuanced understanding of the impacts of climate change on all 169 SDG targets. Global application of the framework reveals that adaptation of wetlands, rivers, cropland, construction, water, electricity, and housing in the most vulnerable countries is required to safeguard achievement of 68% of SDG targets from near-term climate risk by 2030. We discuss how our framework can help align National Adaptation Plans with SDG targets, thus ensuring that adaptation advances, rather than detracts from, sustainable development

The developmental effects of media-ideal internalization and self-objectification processes on adolescents’ negative body-feelings, dietary restraint, and binge eating

Despite accumulated experimental evidence of the negative effects of exposure to media-idealized images, the degree to which body image, and eating related disturbances are caused by media portrayals of gendered beauty ideals remains controversial. On the basis of the most up-to-date meta-analysis of experimental studies indicating that media-idealized images have the most harmful and substantial impact on vulnerable individuals regardless of gender (i.e., “internalizers” and “self-objectifiers”), the current longitudinal study examined the direct and mediated links posited in objectification theory among media-ideal internalization, self-objectification, shame and anxiety surrounding the body and appearance, dietary restraint, and binge eating. Data collected from 685 adolescents aged between 14 and 15 at baseline (47 % males), who were interviewed and completed standardized measures annually over a 3-year period, were analyzed using a structural equation modeling approach. Results indicated that media-ideal internalization predicted later thinking and scrutinizing of one’s body from an external observer’s standpoint (or self-objectification), which then predicted later negative emotional experiences related to one’s body and appearance. In turn, these negative emotional experiences predicted subsequent dietary restraint and binge eating, and each of these core features of eating disorders influenced each other. Differences in the strength of these associations across gender were not observed, and all indirect effects were significant. The study provides valuable information about how the cultural values embodied by gendered beauty ideals negatively influence adolescents’ feelings, thoughts and behaviors regarding their own body, and on the complex processes involved in disordered eating. Practical implications are discussed

Financial crises and the attainment of the SDGs: an adjusted multidimensional poverty approach

This paper analyses the impact of financial crises on the Sustainable Development Goal of eradicating poverty. To do so, we develop an adjusted Multidimensional Poverty Framework (MPF) that includes 15 indicators that span across key poverty aspects related to income, basic needs, health, education and the environment. We then use an econometric model that allows us to examine the impact of financial crises on these indicators in 150 countries over the period 1980–2015. Our analysis produces new estimates on the impact of financial crises on poverty’s multiple social, economic and environmental aspects and equally important captures dynamic linkages between these aspects. Thus, we offer a better understanding of the potential impact of current debt dynamics on Multidimensional Poverty and demonstrate the need to move beyond the boundaries of SDG1, if we are to meet the target of eradicating poverty. Our results indicate that the current financial distress experienced by many low-income countries may reverse the progress that has been made hitherto in reducing poverty. We find that financial crises are associated with an approximately 10% increase of extreme poor in low-income countries. The impact is even stronger in some other poverty aspects. For instance, crises are associated with an average decrease of government spending in education by 17.72% in low-income countries. The dynamic linkages between most of the Multidimensional Poverty indicators, warn of a negative domino effect on a number of SDGs related to poverty, if there is a financial crisis shock. To pre-empt such a domino effect, the specific SDG target 17.4 on attaining long-term debt sustainability through coordinated policies plays a key role and requires urgent attention by the international community