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Fujita, Ochmachi et al combine a DNA origami approach with darkfield microscopy and AFM to study conformational changes in muscle myosin. They generate DNA origami-based thick filaments that enable the direct visualisation of mechanistic details of myosins during force generation under geometric conditions that resemble those in muscle.
Amr Ghaleb et al. find that, in an ErbB2 mouse model, irradiation of premalignant mammary lesions enhances tumorigenesis in tumours that are heterozygous for p53 containing a p53 R172H mutation. This is associated with loss of the wild-type p53 allele, stabilisation of mutant p53 protein and activation of mTOR signaling.
The International Glaucoma Genetics Consortium reports a genome-wide association study meta-analysis of optic disc parameters relevant to primary open-angle glaucoma. They identify two novel variants in PPP1R36-PLEKHG3 and SERPINE3 by multi-trait analysis in European-ancestry cohorts that were replicated in independent Asian cohorts.
Puli Chandramouli Reddy et al. characterize the Wnt signalling regulatory network involved in the formation of head organization in Hydra. They find that Margin, a Wnt-regulated homeodomain transcription factor plays a key role in body axis patterning.
Damry et al. evaluates the impact of individual substitutions in primary sequence of a globular protein on its conformational dynamics. They demonstrate that only two mutations in core residues of a streptococcal protein (Gβ1) variant can synergistically create conformational exchange, one destabilizing the native structure while the other allowing two new conformational states to be accessed on the energy landscape.
Suleiman et al. use “reverse discovery” approach to identify four bacterial species that were enriched on the UV filter octocrylene, two of which (Mycobacterium agri and Gordonia cholesterolivorans) can form biofilms on its surface. They also report that cultivation for 10 days with Mycobacterium agri decreases octocrylene concentration by 19%.
Karen Rihani et al. demonstrate that fruit flies need an odorant-binding protein OBP19b, which is highly expressed in taste sensilla, to prefer select amino acids such as essential l-phenylalanine. This study provides insights into the mechanisms by which insects ensure their dietary intake of essential amino acids.
Claire Chewapreecha et al. combine 753 newly sequenced Thai Burkholderia pseudomallei isolates with 258 Australian isolates to identify genes associated with either clinical or environmental strains. They find 47 genes, 12 of which replicate in both locations, that may provide clues to the strategy used by this microbe to adapt to survive in wide range of ecological niches, including human hosts.
Endow et al. find that protrusions associated with quiescent neural stem cells and intestinal stem cells in Drosophila contain clustered mitochondria. Live imaging and drug treatment provide evidence that mitochondrial positioning is microtubule-dependent. The authors suggest the protrusions function in niche communication.
Fujita et al. demonstrate that a TonB-dependent receptor (TBDR) is involved in the outer membrane transport of lignin-derived biphenyl in a Gram-negative bacterial strain capable of degrading lignin-derived aromatic compounds. They also show that overexpression of corresponding TBDR gene enhances uptake of the compound, providing basis for establishing engineered strains optimized for use in lignin valorization.
Imai et al. show that the light-dependent activation of a proton transporter, Delta-rhodopsin, reverses the pathology caused by the loss of a Parkinson’s disease-associated gene, improving motor behaviors of flies. This study suggests that maintaining the mitochondrial proton-motive force may serve as a therapeutic strategy for Parkinson’s disease.
Thomas et al. uses ancestral sequence reconstruction (ASR) tool to reconstruct functional ancestors of the Mycobacterial and Nocardial CAR1 orthologues, representing one of the largest reconstructed proteins to date. These ancestral CARs display varied tolerances to solvents, pH and in vivo-like salt concentrations along with high thermostability compared to well-studied extant CARs.
Belorusova et al. use HDX-MS to identify specific regions of liver X receptors LXRα/β which differentially correlate with anti-atherogenic and lipogenic activities of ligands. They also show that their differential stabilisation can allow the separation of beneficial anti-atherogenic from adverse lipogenic effects and thus help in the design of drugs with improved therapeutic indexes.
Taherian et al. show a correlation between the severity of apnea-hypopnea and the adjusted pressure coefficient. This study suggests that anatomy-based models coupled with computational fluid dynamics may serve to identify biomarkers that report the severity of sleep obstruction.
Shoichi Nakamura, Seiji Hira et al. demonstrate that a truncated form of Mamo lacking the BTB/POZ domain (MamoAF) is a potent transcriptional activator of a germline gene vasa. This study suggests that MamoAF cooperates with transcriptional activators CBP and OvoB to regulate the development of germline cells.
Özbay et al. show the contribution of fluctuations in sympathetic activation on global fMRI signals in human brain during sleep. Such an inference is based on simultaneously acquiring and correlating EEG K-complexes and episodic drops in finger skin signatures with BOLD-fMRI changes during sleep.
Makoto Nagano et al show that in budding yeast, endosome formation requires vesicle transport from the Golgi. They find that endocytic internalisation is not needed for activation of the key early endosome regulator Rab5, but instead this involves the recruitment of the Rab5 GEF Vps9p to the trans-Golgi network and its subsequent shuttling to the endosome.