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Every mammal studied to date has been found to have a male mutation bias: male parents transmit more de novo mutations to offspring than female parents, contributing increasingly more mutations with age. Although male-biased mutation has been studied for more than 75 years, its causes are still debated. One obstacle to understanding this pattern is its near universality—without variation in mutation bias, it is difficult to find an underlying cause. Here, we present new data on multiple pedigrees from two primate species: aye-ayes (Daubentonia madagascariensis), a member of the strepsirrhine primates, and olive baboons (Papio anubis). In stark contrast to the pattern found across mammals, we find a much larger effect of maternal age than paternal age on mutation rates in the aye-aye. In addition, older aye-aye mothers transmit substantially more mutations than older fathers. We carry out both computational and experimental validation of our results, contrasting them with results from baboons and other primates using the same methodologies. Further, we analyze a set of DNA repair and replication genes to identify candidate mutations that may be responsible for the change in mutation bias observed in aye-ayes. Our results demonstrate that mutation bias is not an immutable trait, but rather one that can evolve between closely related species. Further work on aye-ayes (and possibly other lemuriform primates) should help to explain the molecular basis for sex-biased mutation. 

Abstract The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying the ‘glutamine addiction’ of cancer cells. They are the targets of anti-cancer drugs; however, their mechanisms of activation and catalytic activity have been unclear. Here we demonstrate that the ability of GAC and GLS2 to form filaments is directly coupled to their catalytic activity and present their cryo-EM structures which provide a view of the conformational states essential for catalysis. Filament formation guides an ‘activation loop’ to assume a specific conformation that works together with a ‘lid’ to close over the active site and position glutamine for nucleophilic attack by an essential serine. Our findings highlight how ankyrin repeats on GLS2 regulate enzymatic activity, while allosteric activators stabilize, and clinically relevant inhibitors block, filament formation that enables glutaminases to catalyze glutaminolysis and support cancer progression. 

Abstract The interaction between nuclear receptor coactivator 4 (NCOA4) and the iron storage protein ferritin is a crucial component of cellular iron homeostasis. The binding of NCOA4 to the FTH1 subunits of ferritin initiates ferritinophagy—a ferritin-specific autophagic pathway leading to the release of the iron stored inside ferritin. The dysregulation of NCOA4 is associated with several diseases, including neurodegenerative disorders and cancer, highlighting the NCOA4-ferritin interface as a prime target for drug development. Here, we present the cryo-EM structure of the NCOA4-FTH1 interface, resolving 16 amino acids of NCOA4 that are crucial for the interaction. The characterization of mutants, designed to modulate the NCOA4–FTH1 interaction, is used to validate the significance of the different features of the binding site. Our results explain the role of the large solvent-exposed hydrophobic patch found on the surface of FTH1 and pave the way for the rational development of ferritinophagy modulators. 

ABSTRACT We present six whole community shotgun metagenomic sequencing data sets of two types of biological soil crusts sampled at the ecotone of the Mojave Desert and Colorado Desert in California. These data will help us understand the diversity and function of biocrust microbial communities, which are essential for desert ecosystems. 

The U.S. community corrections system supervises and provides services for nearly 4.4 million individuals. This study explored agency responses during the COVID-19 pandemic using data from 347 surveys of community supervision directors. We examined whether agency and local geographical factors were associated with increased use of telehealth services for mental health, substance use disorders, and criminal behavior. We also assessed whether these factors were significant predictors of changes in agencies’ supervision strategies. Findings indicated a positive association between prepandemic access to telecommunications technology and use of telehealth services, with observed differences regarding urbanicity and type of agency. Agencies with more COVID-19 mitigation strategies tended to avoid in-person contact. Given the vast needs and increased risks present within the community supervision population, it is important to understand the barriers and facilitators associated with innovation and change in the post-COVID-19 era to inform future reform efforts. 

Abstract Reaction of [CuH(PPh₃)]₆with 1 equiv. of Tl(OTf) results in formation of [Cu₆TlH₆(PPh₃)₆][OTf] ([1]OTf]), which can be isolated in good yields. Variable‐temperature¹H NMR spectroscopy, in combination with density functional theory (DFT) calculations, confirms the presence of a rare Tl−H orbital interaction. According to DFT, the¹H chemical shift of the Tl‐adjacent hydride ligands of[1]⁺includes 7.7 ppm of deshielding due to spin‐orbit effects from the heavy Tl atom. This study provides valuable new insights into a rare class of metal hydrides, given that[1][OTf]is only the third isolable species reported to contain a Tl−H interaction.