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Using co-culture experiments and mathematical modelling, Paczkowski et al discover that prostate cancer spheroids comprising mixed tumour cell populations display enhanced growth and reduced radiation sensitivity due to competitive and antagonistic interactions between cell populations. This interdisciplinary approach reveals a role for ecological-type interactions in the radiation response and may be used to study other cancer types.
Nick Fountain-Jones et al. use genomic and spatial data to examine how urbanization affects the spread of the pathogen feline immunodeficiency virus in pumas from areas of varying anthropogenic development. Their results show that landscape variables and host gene flow explained significant amounts of variation in virus spread in a region bounded by urban development but did not in a more wild landscape, demonstrating how anthropogenic landscapes can alter pathogen spread.
Palayam, Ganapathy, Guercio et al. determine the crystal structure of the photosensory domain of Arabidopsis Cryptochrome-2 (CRY2) in a tetrameric active state, identifying critical residues that participate in photo-induced oligomerization of CRY2. This study offers an updated model of CRY’s photoactivation mechanism.
Jiang et al. show that nitrogenase NifH component of Hydrogenobacter thermophilus fulfils the quantity and functional requirements to engineer efficient N2 fixation in mitochondria. This study contributes towards future efforts engineering diazotrophs in eukaryotic cells.
Makoto Hibi et al. report a novel three-component monooxygenase system in Rhodococcus wratislaviensis. This enzyme catalyzes the activation of an inert C–H bond and may be potentially important as a biocatalyst for industrial applications.
Baillet et al. use the cynomolgus monkey model to model Lassa virus and associated Lassa fever (LF). They provide a full characterisation of LF pathogenesis with the aim of assisting the development of early diagnostic tools.
Layer et al. present a crystal structure of Naa20, the catalytic subunit of an N-terminal acetyltransferase NatB, in complex with its competitive inhibitor CoA-Ac-MDEL. They find that Naa20 alone can acetylate NatB in vitro while Naa25, the auxiliary subunit of Naa20, increases the substrate affinity of Naa20. This study provides insights into the development of NAT inhibitors.
Yunhui Zhou and Yuguo Yu propose a continuous-time eye movement model capable of predicting both eye fixation location and duration. Their model accounts for saccadic inaccuracy/bias and memory constraints and, applied to real data, shows that humans may use an eye movement strategy that balances task performance and costs when searching for a target.
Futrega et al. challenge the long established chondrogenic differentiation protocol used to induce bone marrow-derived stromal cell (BMSC) differentiation which presumes the need for more than 2 weeks of continuous TGF-β1 exposure. Using a micro-pellet model, they show that BMSC differentiation is triggered by a single day of TGF-β1 exposure.
Niederdorfer et al. show that different anaerobic ammonium oxidizing (anammox) bacterial species and other key biofilm taxa vary in their transcriptional responses as a function of temperature and dissolved oxygen disturbances in an engineered ecosystem. This study highlights the links between microbial community stress response, individual stress response, and process level failure in anammox mainstream wastewater treatment.
Cai and colleagues sequence and annotate the genome of the yellowstripe goby at the chromosome level. Combining genome and transcriptome data, they infer key metabolic pathways for high lipid accumulation in the liver of this fish.
Here, the authors discover that NGF, upregulated by transcription factor ZBTB46 in prostate cancer exposed to androgen therapy, promotes neuroendocrine differentiation. They show that NGF interacts with the GPCR CHRM4, that both NGF and CHRM4 are upregulated in highly metastatic prostate cancer and that targeting NGF reduces therapy resistance in a mouse xenograft model.
Savva et al. investigate the sex dependent effect of maternal obesity on the metabolism of offspring. They find that metabolic changes are conferred on a sex basis, with males suffering from impaired lipid metabolism relative to females when born to obese mothers, using a lipidomic approach.
Zhao et al. demonstrate the effect of elevated extracellular K + on hidden hearing loss in mice, and the consequent effect on inner hair cell ribbon synapse loss. Their results indicate that BK potassium channels could be a potential target for treatment of hidden hearing loss.
Li, Cebrian et al. show that a combination of peptide D-11 and vancomycin exhibits a potent antimicrobial activity against a panel of Gram-negative pathogens without apparent toxicity. They find that this combination is also effective in clearing Pseudomonas aeruginosa in mice, providing a potential antimicrobial therapy for humans.
Dowsett et al use a single-cell resolution approach to analyse the distribution of mutations across several divisions in yeast diploid strains mutated in mismatch repair and polymerase delta proofreading. They find that the underlying mutation rate varies from one division to another, and that new mutations segregate unequally between sister chromatids at each division, expanding genetic heterogeneity in the population.
Kato, Abdollahi et al. identify a redox protein thioredoxin and mitochondrial fission-1 (FIS1) protein as miR-379 targets in mouse kidney. They find that miR-379 knockout mice are protected from diabetic kidney disease by enhancing mitophagy via FIS1, suggesting miR-379 as a potential therapeutic target for diabetic kidney disease.