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Luo, Zhou et al. show that Bedaquiline (BDQ, Sirturo), approved to treat multi-drug-resistant tuberculosis, inhibits the yeast and human mitochondrial ATP synthases in addition to its intended target, the Mycobacterium tuberculosis ATP synthase. The structure of the mitochondrial ATP synthase bound to BDQ suggests a means to modify this inhibitor to increase its specificity for the M. tuberculosis enzyme, thereby reducing its side effects for patients.
Habowski et al. develop a sorting protocol for purification and comparative analysis of mouse colon stem cells and their progeny. By proteomic and transcriptomic analysis, they determine that lineage commitment is accompanied by a greater change in mRNA splicing and polyadenylation than in gene expression and they characterise signalling pathways involved in differentiation.
Wikström and Springett analyze the thermodynamic efficiency of redox reactions and proton translocation by the complexes of mitochondrial respiratory chain. They report that the thermodynamic efficiency is about 80–90% and that the degree of coupling between the redox and proton translocation reactions is very high during active ATP synthesis, but decreases when ATP synthesis stops.
Deng-hai Zhang et al. report a network pharmacology analysis of the Traditional Chinese Medicine (TCM) lung-cleaning and toxicity-excluding (LCTE) soup. By exploring the chemical compounds that make up LCTE and the likely pathways and proteins that they target, the authors show that LCTE may have the potential to directly inhibit the SARS-CoV-2 virus and relieve inflammatory symptoms.
Koike et al. show that the 2-nitroimidazole doranidazole increases radiation-induced DNA damage in hypoxic glioma stem cells (GSCs). They further demonstrate that additional radiation-independent cytotoxicity of 2-nitroimidazoles is due to ferroptosis that occurs through blockade of mitochondrial complexes I and II leading to metabolic changes in the oxidative stress response.
Kazazian and colleagues identify FAM46C/TENT5C as an interactor and negative regulator of PLK4 activity in centriole duplication. The authors also find that FAM46C expression strongly reduces cancer cell invasion, uncovering a role for FAM46C as tumor suppressor.
David Baracchi et al. show that honey bees exposed to geraniol, a component of an attractant pheromone, exhibit improved olfactory learning and memory while the opposite effect was seen in honey bees exposed to the aversive pheromone, 2- heptanone. These changes occurred through a modulation of appetitive motivation without affecting odor processing, suggesting an important role for pheromones as modulators of motivational and learning processes.
Thomas Conrad et al. identify sequences downstream of transcription start sites that affect T7 promoter activity and use this to generate promoter variants with enhanced transcriptional output. They use the optimized promoters to prepare cDNA libraries for single-cell RNA sequencing with increased complexity compared to those prepared with standard T7 promoters.
Tanabe, Fujii, Okada-Iwabu, Iwabu et al. report the crystal structures of the D208A variant of human adiponectin receptor AdipoR1 as well as the revised structures of the wild-type AdipoR1. These structures clarify the interconversion between the open and closed states of this protein, which may be relevant to its function.
Wu et al. provide insight to the role of acetyl coenzyme A in regulating N-acetylation in insect AANAT using ITC and NMR methods. These results provide useful data on the structural function of insect AANATs.
Kim et al. use RNAseq of two watermelons to select candidate genes coding for enzymes that catalyze modifications of cucurbitacins. They characterise four of the 16 candidate enzymes (3 different acetyltransferases and one UDP-glucosyltransferase) by HPLC, LC-MS, NMR, and in vitro enzymatic assay. They further show with in vivo assay in Drosophila, that acetylation of cucurbitacin increases neuronal activity in insects.
Benjamin Simpson et al. use publicly available cancer genomic data to investigate copy number changes at the 3q26.31–32 locus, which has been associated with aggressive prostate cancer based on single-nucleotide polymorphisms. They find that gains of NAALADL2 and TBL1XR1 in this locus are associated with more aggressive subtypes of prostate cancer and the transcription of pro-proliferative signalling processes.
Ergal et al. report that biohydrogen production from glucose by an engineered microbial consortium of Clostridium acetobutylicum and Enterobacter aerogenes can be 40% higher than the “Thauer limit”. They further show that the volumetric H2 production rates of their system are superior compared to any mono-, co- or multi-culture system reported to date.
Pedro R. Frade et al. analyze published bacterial data and environmental data from the eReefs platform to study bacterioplankton community dynamics across the Great Barrier Reef. They identify communities within inshore and outershelf reefs that are susceptible to nutrient and temperature changes, highlighting the importance of understanding microbial ecosystems dynamics informing reef health.
Rugema, Garland-Kuntz et al. report the 2.7 Å crystal structure of a fragment of a catalytically active PLCε in which the RA1 domain is integrated into the core. They find that a conserved amphipathic helix in the autoregulatory X–Y linker of PLCε modulates its catalytic activity in cells. This study provides structural insights into the regulation of this essential cardiovascular enzyme.
Marc A. Beal, Matt J. Meier et al. use a transgenic rodent model with NGS to inform mutational signature analyses. They analyze lacZ mutations from the bone marrow of MutaMouse animals exposed to chemical mutagens. They report that lacZ sequencing generates chemical-specific mutation signatures observed in human cancers with established environmental causes.
Danyang Wang and Yina Ma measure the amount of money participants are willing to forgo for the opportunity to access social or non-social evaluations of the self. They show that subjective values on knowing social evaluation is valence-dependent whereas that on non-social evaluation is valence-insensitive. Moreover, oxytocin contributes to valence-dependent valuation on social evaluation.
Kuwabara et al. identify a novel long intergenic noncoding RNA (lincRNA), termed Lionheart, upregulated in pressure overloaded hearts in mice. Deleting this gene results in decreased systolic function and reduction in MYH6 protein levels following pressure overload. They demonstrate that Lionheart interacts with PURA, preventing its binding to the promoter region of Myh6 locus, leading to reduced MYH6 protein expression.
Ravindran et al. report the construction of synthetic immediate-early genes (SynIEGs), target genes of the Erk signaling pathway. SynIEGs implement user-defined regulation while tracking transcription and translation. This study underscores post-transcriptional regulation in signal decoding that may be masked by analyses of RNA abundance alone.
