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Leila Valanejad et al. report increased expression of modified tumor suppressor proteins (TSPs) with loss of tumor suppressor activity in aggressive, chemotherapy-resistant hepatoblastoma. They find that TSP upregulation occurs via PARP1-mediated chromatin remodeling, leading to activation of multiple cancer-associated pathways.
Lisa Traeger et al. show that human hereditary hemochromatosis protein (HFE) signals through ALK3 to induce hepcidin in mice in vivo. The results validate and extend previous findings from in vitro studies that suggested a link between HFE and BMP signaling.
Pablo Carbonell et al. present an automated pipeline for the discovery and optimization of biosynthetic pathways for microbial production of fine chemicals. They apply their pipeline to the production of the flavonoid (2S)-pinocembrin in Escherichia coli and show improvement of the pathway by 500-fold.
Luo-Li et al. show that humans and cat cortical neurons respond faster to slowly moving light stimuli than to dark stimuli, contrary to previous findings for responses to stationary stimuli. The results may explain why ON visual pathways are used for slow-motion image stabilization in many species.
Parker Nichols et al. present an exact nuclear Overhauser enhancement (eNOE) protocol for defining small RNA structures at high resolution using only NOE distance data. They apply eNOE to a 14-mer UUCG tetraloop structure, obtaining a decrease in root-mean-square deviation from 1.52 Å to 0.44 Å, compared to conventional NOE.
Mitesh Dongre et al. have identified a novel bacterial cytotoxin from Vibrio chloerae, whose virulence depends on flagella-mediated secretion. This suggests that the flagella’s role in cytotoxin export could improve survival and proliferation of bacteria when exposed to environmental stress.
David Duffy et al. use a precision-medicine-based approach to study fibropapillomatosis tumors in sea turtles to identify environmental triggers and potential therapeutics. They show that these tumors share genetic similarities with human cancer types, and may be treatable using human anti-cancer therapies.
Benjamin Turner et al. report an assessment of replicability of task-based fMRI studies as a function of sample size. They find that the degree of replicability for typical samples sizes reported in the literature is modest and advocate for standards requiring larger sample sizes, potentially in excess of N = 100.
Eric Aird et al. present a strategy to increase the efficiency of homology-directed repair in CRISPR/Cas9-mediated genome editing. They show that tethering a single-stranded oligodeoxynucleotide to the ribonucleoprotein complex using a fused HUH endonuclease increases editing efficiency by up to 30-fold.
Serra Ongun, Angela Sarkisian and David McKemy show that localized co-injection of lidocaine derivative QX-314 and receptor agonists is able to block cold sensitivity in mice in a targeted way, with implications for treating cold pain associated with injury and disease.
Jocelyn Colella et al. report whole-genome sequences of 10 stoats (Mustela erminea) from four regions of glacial refugia. They find evidence for two past introgressive events between lineages that coincide with interglacial periods, a pattern that may extend to other high–latitude species.
Craig Albertson et al. report a study of the genetic basis of scale shape variation in cichlids from Lake Malawi. They find 40 QTL for scale development, most of which are specific to distinct body locations, and a role for Fgf signaling in shaping cichlid scales.
Shinya Sugimoto et al. demonstrate how molecular chaperone DnaK regulates biofilm formation through the production of curli, which anchor enteric bacteria to the biofilm. This finding provides mechanistic insights into the development of anti-biofilm agents as antibiotics.
Krishnarjuna et al. show that multiple transient interactions mediate monoclonal antibody recognition of an epitope within a disordered malaria antigen, MSP2. These results explain the antibody’s differential affinities for two allelic forms of the antigen.
Yichen Ding et al. identify a novel integrative and conjugative element that confers Pseudomonas aeruginosa with resistance to carbapenem, the last-resort drug for susceptable Gram-negative bacterial infections. This study also shows how antivirulence treatment for P. aeruginosainfections can be challenged by horizontal gene transfer.
Konstantinos Hatzikotoulas et al. report the largest genome-wide association study to date for developmental dysplasia of the hip using national clinical audit data from the UK. They find a significant association with the GDF5 locus and evidence for shared genetic architecture with hip osteoarthritis.
Yoshitaka Kamimura and colleagues combine live-imaging technology with microfluidics to examine chloroplast DNA organization in nucleoids. They find that these structures form a network structure in dividing chloroplasts, and propose a mechanism for their inheritance in organelle replication.
Gudjon Oskarsson et al. report the association of a rare variant in the erythropoietin (EPO) receptor gene, EPOR, with serum EPO levels in the Icelandic population. The variant leads to a truncation of EPO-R without an effect on hemoglobin levels, indicating a possible feedback mechanism in the generation of red blood cells.
Jun Zhao, Evan S. Krystofiak, and colleagues identified a new cis interface (Cis-1) essential for the formation of normal tight junctions. This study suggests that Cis-1 contributes to maintaining structural flexibility of tight junction strands for proper ion balance and hearing.
Nicholas Perkons et al. investigate the mechanism by which electrolytic ablation induces cell death in the localized treatment of tumors. They find that electrolytic ablation alters the pH buffering capacity of the tumor microenvironment to induce cellular necrosis.