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Cheng Dong et al. resolve the crystal structure of NTMT2, presenting the molecular basis for substrate recognition. Using structural and biochemical studies, they identified a specific residue within NTMT2 that controls its binding affinity to unmethylated or monomethylated substrates.
Fan Zhang et al. present CRISPRminer, a comprehensive database for exploring CRISPR-Cas systems in more than 3500 microbial species and a web-server for in-depth data mining. CRISPRminer allows researchers to predict CRISPR-Cas systems and investigate self-targeting CRISPRs, microbe-phage interaction networks, and anti-CRISPR features.
Anna Biernacka, Yingjie Zhu et al. present i-BLESS, a universal method for detecting genome-wide DNA double strand breaks, optimized here for yeast. By immobilizing cells on agarose beads, the authors are able to achieve efficient diffusion of reagents and labeling of double strand breaks, including ultra-rare breaks such as those at G-quadruplexes.
Rachel Graham et al. show that coronaviruses with extensively rewired transcription regulatory networks are effective vaccine candidates against Severe Acute Respiratory Syndrome Coronavirus. The reversion of live-attenuated vaccine strains to virulence can be avoided with these vaccines.
Chun-Ting Cheng et al. demonstrate that arginine starvation kills arginine-auxotrophic cancer cells by depleting them of aspartate through asparagine synthetase (ASNS) and disrupting their mitochondrial metabolism. This study presents ASNS-induced aspartate depletion as an anti-cancer therapeutic strategy.
Hui Ma et al. report a new mechanism by which activated hepatic stellate cells promote the epithelial-to-mesenchymal transition (EMT) in hepatocellular carcinoma. They find that transglutaminase 2 is upregulated by activated hepatic stellate cells via inflammatory signalling, which leads to a pseudohypoxic state promoting EMT.
Samadhan Patil et al. report a new method for improving the sensitivity and reproducibility of mechanobiological measurements in malignant cancer cells. Their findings provide insight into the interaction of cells with each other and the microenvironment and may impact our understanding of metastasis.
James Dai et al. report the first whole-genome sequencing study of esophageal adenocarcinoma (EAC) in Chinese patients. They find distinct genomic alterations and signatures compared to EAC in patients from Western countries.
Shi Yu et al. show that the dynamics of fluorescently labeled DNA loci and cytoplasmic particles in E. coli respond differently to mechanical compression of the cell. These results suggest DNA elasticity is more important for determining the diffusivity of DNA loci in response to mechanical force than is cytoplasmic viscoelasticity.
Philip Miller et al. present an approach for extracting dermal interstitial fluid (ISF) using an array of hollow microneedles in a cylindrical substrate that minimizes skin compression and tissue damage. They extract larger volumes of ISF suitable for downstream analyses, compared to previous reports.
Kun Wang et al. present a genomic analysis identifying incomplete lineage sorting and hybridization in the mitochondrial DNA of the European bison (wisent). They find that incomplete lineage sorting is the most feasible explanation for the phylogenetic heterogeneity observed in Bovidae.
Marina Shenkman et al. show that the ERAD mannosidases EDEM1 and EDEM2 have bona fide mannosidase activity in vitro. The activity of these enzymes is substantially faster when their glycoprotein substrates are in the unfolded state, suggesting a mechanism for efficient ERAD targeting of unfolded or misfolded glycoproteins.
Dipali Mhaindarkar et al. examine the functional effects of a salt bridge loss in the active site of glycosyl hydrolase Bg1M-G1, found in the metagenome of a seasonally cold marine habitat. They show that the catalytic efficiency is overall higher with the lost salt bridge, trading off with lower thermal stability.
Omar Cornejo et al. report a genomic analysis of 200 cacao plants (Theobroma cacao L.) representing more than 10 genetically distinct populations. They identify metabolic and disease resistance genes as contributing to the domestication of cacao and show that domesticated populations maintain a high proportion of deleterious mutations.
Catherine Colas des Francs-Small et al. used an engineered pentatricopeptide repeat protein to induce cleavage of nad6 mRNA in the mitochondria of Arabidopsis thaliana, eliminating its expression. The approach has potential for use in functional characterization of mitochondrial genes and future agricultural applications.
Ritsuko Takada et al. show that Wnt3a assembles into high molecular weight complexes that restrict the diffusion of Wnt within Xenopus embryos. These results suggest that Wnt diffusion in cells is controlled by a balance between higher order complex assembly and dissociation by Wnt-binding proteins.
Simone de Jong et al. examine the balance of common and rare risk for psychiatric disorders in a large family with high incidence of Bipolar Disorder and Major Depressive Disorder. They find that increased polygenic risk over generations could be partially due to assortative mating, which may explain the observation of anticipation in mood disorders.
Stefan Reuscher et al. assembled the genome of an African wild rice species to facilitate breeding efforts and functional genomic studies. They used SMRT sequencing, chromosomal synteny between rice species, and a linkage map to assemble the 351 Mb genome into 12 chromosomes.
Luba Perry et al. report transplantation of engineered prevascularized human muscle into mice to repair an abdominal muscle defect. They show that genetically engineering smooth muscle cells to secrete VEGF and endothelial cells to secrete ANGPT1 significantly improves host neovascularization and myogenesis.
Roy et al. showed that activation of parvocellular pre-autonomic oxytocin neurons increased sympathetic nerve activity following myocardial infarction. This and other aberrant physiological changes induced by acute myocardial infarction were decreased by oxytocin receptor antagonists, hinting to their potential therapeutic role.