Research articles

Quantification of genomic responses to environmental stimuli by current genome-scale assays is limited to indirect measurements or requires knowledge of the transcription factors involved. Here, the authors use genome-wide high-throughput reporter assays to agnostically map enhancer activity in response to glucocorticoid treatment across the human genome.

Genome-wide libraries for CRISPR knockout, interference, and activation have allowed the systemic interrogation of gene function. Here, the authors evaluate the Brunello CRISPRko library and introduce Dolcetto and Calabrese for CRISPRi and CRISPRa, respectively.

The origin of Tibetan barley (qingke) has been a controversial issue for many years. Here, the authors conduct population genomics study to support that qingke is derived from eastern domesticated barley instead of Tibetan wild barley and suggest southern Tibetan Plateau as its introduction route.

Tr1 cells are considered an immunosuppressive CD4 T cell population producing IL-10. Here the authors show that IL-10 is insufficient for Tr1 immunosuppression, define surface markers and transcriptional program of the immunosuppressive subset within Tr1, and reveal its deficiency in patients with IBD.

Transient aneuploidy enables cells to survive sudden environmental changes before longterm cellular adaptations are established. Here, the authors show that yeast cells respond to the acute loss of Ulp2 SUMO protease by rapid induction of aneuploidy, and reveal predictable long-term adaptation mechanisms that restore euploidy.

Alkaline ceramidases (ACERs) are a class of poorly understood transmembrane enzymes controlling the homeostasis of ceramides. Here authors solve the Xray structure of human ACER3 and uncover a Ca2+ binding site providing an explanation for the known regulatory role of Ca2+ on ACER3 activity.

In standard SERS the probability for the molecules to reach tiny hotpot regions is low. Here, the authors introduce an approach based on warped spaces that offers a strategy to manipulate hotspots of metallic nanostructures, resulting in large broadband enhancements in both the magnitude and the volume size.

Membrane separation is important for a range of industrial and medical applications. Here, the authors report on the formation of self-assembled protein membranes for size selective separation and demonstrate application in the separation of dyes, nanoparticles and in hemodialysis.

Specific cancer cell vulnerabilities can provide an opportunity for the development of novel cancer therapeutics. In this study the authors demonstrate that targeting ADAR1 represents a potential therapeutic vulnerability in cancers with activated interferon response signatures.

Secreted cytokine decoy receptors encoded by viruses can act as potent immune evasion proteins modulating antiviral immunity. Here Hernaez et al. show that cell surface binding is required for efficient evasion of the host response by a secreted virus encoded type I IFN decoy receptor of vaccinia and ectromelia virus using an in vivo model of infection.

Development of fuel cells and metal-air batteries is hindered by electrocatalyst performance, which can be enhanced with uniform and atomically dispersed active sites. Here the authors report an iron-based electrocatalyst for oxygen reduction in cathodes for a zinc-air battery and a hydrogen-air fuel cell.

Replication Protein A (RPA) coats single stranded DNA (ssDNA) generated during DNA recombination, replication and repair. Here the authors present a structural model suggesting how RPA’s DNA-binding domains promote cooperative assembly of multiple RPAs on long ssDNA.

Substrate reduction therapies (SRT) are a promising therapeutic approach for monogenic inherited metabolic diseases. Here the authors evaluate the therapeutic potential of an in vivo CRISPR/Cas9-mediated SRT to treat primary hyperoxaluria type I and demonstrate its safety and efficacy.

There are currently no effective therapies available for acute kidney injury (AKI). Here the authors generate molybdenum-based polyoxometalate nanoclusters and show that these have preferential renal uptake and can ameliorate AKI pathology in mice by scavenging reactive oxygen species.

The potential impact of neonicotinoid field exposure on bumblebee microbiota remains unclear. In a landscape—scale study, Wintermantel et al. show that whilst exposure to clothianidin impacts Bombus terrestris performance, it does not affect levels of gut bacteria, viruses or intracellular parasites.

Mutations within immunological epitope containing regions of influenza A virus can impair the established immune response between influenza strains and could impact rational vaccine design. Here Grant et al. examine the presence, structural impact and cross reactivity of two human immunodominant influenza epitope variants.

Packaging of viral DNA depends on strong molecular motors that are powered by ATP hydrolysis. Here, the authors develop a single-molecule assay to monitor how nucleotide binding regulates motor-DNA interactions and reveal a generic mechanism that prevents exit of the whole DNA from the viral capsid during packaging.

It is unclear whether the gut microbiome can mitigate or exacerbate arsenic toxicity. Here, Coryell et al. show that the human gut microbiome protects mice from arsenic-induced mortality, with protection levels correlating with the relative abundance of the human commensal Faecalibacterium.

The bacterial complex QrcABCD plays a key role in the bioenergetics of sulfate respiration. Here, Duarte et al. show that this complex is electrogenic, with protons and electrons required for quinone reduction being extracted from opposite sides of the membrane.

Fires cause large perturbations to terrestrial carbon cycle through direct carbon emissions. Here the authors combine several models and measurement datasets and show that fires can indirectly worsen the carbon loss through the net negative impacts on ecosystem productivity from fire ozone and aerosols.