• Energy Research
• 3. Good health close
• 1. No poverty close
• DE close
• NL close

The adenine nucleotide translocation in mitochondria has previously been established as an exchange between exogenous and endogenous adenine nucleotides across the inner membrane. The specificity and the control of the exchange are examined with the following major results: The adenine nucleotide translocation is relatively specific for exogenous ADP and ATP, AMP being nearly inactive. Among other nucleotides tested, only dADP and dATP exchange with a noticeable activity. In the controlled state ADP exchanges 2–4 times faster than ATP. If simultaneously added, ADP and ATP compete for the exchange, with ADP being about tenfold more active than ATP. The specificity of the exit of adenine nucleotides in the exchange is similar to the specificity of the entrance with the difference that ADP and ATP are released with equal activity in proportion to their intramitochondrial content. AMP is released only after a slow conversion to ADP. Therefore the short time exchange is limited by the endogenous content of ADP plus ATP. The exchange is influenced by the metabolic state of the mitochondria. The ATP exchange is more variable than the ADP exchange. Two effects are elucidated: (a) the influence of the metabolic state on the relative content of AMP which inhibits both the ADP and ATP exchange (b) the coupling of the energy transfer system which inhibits only the ATP exchange. An example for case (a) is the inhibition of the ADP and ATP exchange by arsenate and an example for case (b) is the strong increase of the ATP exchange on uncoupling. The following effects are relevant to the mechanism of the control of the exchange by ATP. The stimulation of the ATP exchange by uncoupler has the same concentration dependence as the uncoupling of oxidative phosphorylation (Km [CCP] = 0.08 μM, where CCP = carbonyl‐cyanide‐phenylhydrazone). Oligomycin does not abolish the uncoupler effect on the ATP exchange. “Endogenous uncoupling” on aging of mitochondria also stimulates the ATP exchange. Valinomycin plus K+ only slightly stimulate the ATP exchange. Anaerobiosis stimulates the ATP exchange to a smaller extent than uncoupling.In competition with ADP the effects of energy transfer on ATP exchange are more strongly revealed. On uncoupling the more than tenfold preference for ADP is fully abolished. It is concluded that basically the exchange for ADP and ATP has equal specificity in forward and reverse reaction. In the controlled state a superimposed force makes the specificity asymmetric and inhibits the entrance of ATP. This control of the ATP exchange is concluded to be based on the anionic character of the adenine nucleotides. Thus the ATP4‐ex–ADP3‐in exchange is inhibited unless the charge difference is compensated for by an uncoupler stimulated H+ movement across the membrane. Furthermore an electric potential gradient appears to be effective in the controlled state which is abolished on uncoupling.

This article presents a model of development, civil war and climate change. There are multiple interactions. Economic growth reduces the probability of civil war and the vulnerability to climate change. Climate change increases the probability of civil war. The impacts of climate change, civil war and civil war in the neighbouring countries reduce economic growth. The model has two potential poverty traps – one is climate-change-induced and one is civil-war-induced – and the two poverty traps may reinforce one another. The model is calibrated to sub-Saharan Africa and a double Monte Carlo analysis is conducted in order to account for both parameter uncertainty and stochasticity. Although the IPCC Special Report on Emission Scenarios (SRES) is used as the baseline, thus assuming rapid economic growth in Africa and convergence of African living standards to the rest of the world, the impacts of civil war and climate change (ignored in SRES) are sufficiently strong to keep a number of countries in Africa in deep poverty with a high probability.

Sustainable development goals (SDGs) adopted in 2015 are geared toward sustainable development through various pathways, one being reducing inequality as covered in SDG 10. Inequalities are a threat to health and wellbeing of populations and a planet Earth in which we live. This rapid review aims to identify key issues that are likely to exacerbate inequalities around the six SDGs directly related to One Health, which are SDG 3, 6, 11, 13, 14 and 15, and suggest some actions that may help to address them using inclusive governance taking into account the coronavirus disease of 2019 (COVID-19) pandemic. Informed by the literature on SDGs and using the “inclusive development concept” by Gupta and Vegelin, literature search was done in Google Scholar, PubMed Central, as well as, searching of references in the relevant articles identified using search terms from the six SDGs that are directly related to One Health. In the context of the SDGs, in order to achieve One Health through inclusive governance, and tackle inequalities, the following needs to be considered and addressed: increasing number of armed conflicts; ongoing COVID-19 pandemic; ensuring availability of water and sanitation facilities; improving city and urban areas planning to cope with climate change; improving governance arrangements for addressing climate change factoring gender and human rights; multisectoral planning for conservation of oceans, seas, and marine resources; balancing trade regulation of wildlife trade with conservation efforts; need for a research collaborative involving experts from environmental sciences, wildlife, agriculture and human health to study and develop scientific evidence on contribution of changes in land use practices to occurrence of zoonotic diseases; and need of a legislation for promoting animal welfare to protect public health. Also, inclusion of people with disabilities in the use of digital technologies is critical.

Abstract Radiation damage in biological systems is initiated by free radicals and progresses with time through a variety of mechanisms. The time-scale and details of these mechanisms are briefly reviewed. Because of the variety of mechanisms of radio-biological damage, any single radio-protective or therapeutic agent can be only partially effective. The potential of and need for simultaneously using several radio-protective and therapeutic agents, including sulfhydryl compounds, superoxide dismutase, antioxidant proteins, and DNA repair enzymes, are examined, based on a priori considerations of the consequences of radiation exposure.

Access to reliable and affordable energy is vital for sustainable development. In the off-grid areas of developing countries, decentralized energy solutions have received increasing attention due to their contributions to reducing poverty. However, most of the rural population in many developing countries still has little or no access to modern energy technologies. This paper assesses the factors that determine the successes and failures of decentralized energy solutions based on local harmonized case studies from heterogeneous contexts from Asia, sub-Saharan Africa, and South America. The case studies were analyzed through the coupled lenses of energy transition and the Water–Energy–Food Security (WEF) Nexus. The findings indicate that access to modern decentralized energy solutions has not resulted in complete energy transitions due to various tradeoffs with the other domains of the WEF Nexus. On the other hand, the case studies point at the potential for improvements in food security, incomes, health, the empowerment of women, and resource conservation when synergies between decentralized energy solutions and other components of the WEF Nexus are present.

Background and Aims: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. Approach and Results: C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD+/NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. Conclusions: Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.

The continual spread of novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), posing a severe threat to the health worldwide. The main protease (Mpro, alias 3CLpro) of SARS-CoV-2 is a crucial enzyme for the maturation of viral particles and is a very attractive target for designing drugs to treat COVID-19. Here, we propose a multiple conformation-based virtual screening strategy to discover inhibitors that can target SARS-CoV-2 Mpro. Based on this strategy, nine Mpro structures and a protein mimetics library with 8960 commercially available compounds were prepared to carry out ensemble docking for the first time. Five of the nine structures are apo forms presented in different conformations, whereas the other four structures are holo forms complexed with different ligands. The surface plasmon resonance assay revealed that 6 out of 49 compounds had the ability to bind to SARS-CoV-2 Mpro. The fluorescence resonance energy transfer experiment showed that the biochemical half-maximal inhibitory concentration (IC50) values of the six compounds could hamper Mpro activities ranged from 0.69 ± 0.05 to 2.05 ± 0.92 μM. Evaluation of antiviral activity using the cell-based assay indicated that two compounds (Z1244904919 and Z1759961356) could strongly inhibit the cytopathic effect and reduce replication of the living virus in Vero E6 cells with the half-maximal effective concentrations (EC50) of 4.98 ± 1.83 and 8.52 ± 0.92 μM, respectively. The mechanism of the action for the two inhibitors were further elucidated at the molecular level by molecular dynamics simulation and subsequent binding free energy analysis. As a result, the discovered noncovalent reversible inhibitors with novel scaffolds are promising antiviral drug candidates, which may be used to develop the treatment of COVID-19.