Evaluating regulatory strategies for mitigating hydrological risk in Brazil through diversification of its electricity mix

Hydroelectricity provides approximately 65% of Brazil’s power generating capacity, making the country vulnerable to droughts, which are becoming increasingly frequent. Current energy law and policy responses to the problem rely on a sectorial approach and prioritise energy security and market regulation. Brazil has opted to increase energy security levels during periods of hydrological variability with national grid interconnection and thermal plants backup. Additionally, Brazil has created the Energy Reallocation Mechanism (MRE) to manage the generators’ financial impacts in times of insufficient water. This policy, however, was unable to avoid the high financial exposure of generators in the spot market during the severe droughts experienced in the period 2013-2017. To explore how a more diversified electricity matrix can contribute to reducing hydrological risk, this article uses Integrated Assessment Modelling (IAM) techniques to analyse future macroeconomic and energy scenarios for Brazil in a global context, aligned with the Brazilian Nationally Determined Contributions (NDC) under the 2015 Paris Agreement on Climate Change. We show that the addition of non-hydro renewables is an advantage from the integrated Water-Energy-Food nexus perspective because it reduces trade-offs amongst the water and energy sectors. Our conclusions suggest that a nexus perspective can provide useful insights on how to design energy laws and policies.Philomathia Foundation; Cambridge Humanities Research Grant

Early‐onset coenzyme Q10 deficiency associated with ataxia and respiratory chain dysfunction due to novel pathogenic COQ8A variants, including a large intragenic deletion

Coenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous subtype of mitochondrial disease. We report two girls with ataxia and mitochondrial respiratory chain deficiency who were shown to have primary CoQ10 deficiency. Muscle histochemistry displayed signs of mitochondrial dysfunction—ragged red fibers, mitochondrial paracrystalline inclusions, and lipid deposits while biochemical analyses revealed complex II+III respiratory chain deficiencies. MRI brain demonstrated cerebral and cerebellar atrophy. Targeted molecular analysis identified a homozygous c.1015G>A, p.(Ala339Thr) COQ8A variant in subject 1, while subject 2 was found to harbor a single heterozygous c.1029_1030delinsCA variant predicting a p.Gln343_Val344delinsHisMet amino acid substitution. Subsequent investigations identified a large‐scale COQ8A deletion in trans to the c.1029_1030delinsCA allele. A skin biopsy facilitated cDNA studies that confirmed exon skipping in the fibroblast derived COQ8A mRNA transcript. This report expands the molecular genetic spectrum associated with COQ8A ‐related mitochondrial disease and highlights the importance of thorough investigation of candidate pathogenic variants to establish phase. Rapid diagnosis is of the utmost importance as patients may benefit from therapeutic CoQ10 supplementation

Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency

Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6-months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only ~ 1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt-tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomic and proteomic analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress response associated with increased FGF21 and GDF15 expression enhances the metabolism modulated by serine biosynthesis, one carbon metabolism, TCA lipid oxidation and amino acid availability, while in the second step mTOR activation leads to increased mitochondrial biogenesis. Our data suggest that the spontaneous recovery in infants with digenic mutations may be modulated by the above described changes. Similar mechanisms may explain the variable penetrance and tissue specificity of other mtDNA mutations and highlight the potential role of amino acids in improving mitochondrial disease