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Borosins are ribosomally encoded and posttranslationally modified peptide (RiPP) natural products featuring amide-backbone α-N-methylation. Here, the authors report the discovery and characterization of type IV borosin ‘split’ pathways encoding distinct, separate α-N-methyltransferases and precursor peptide substrates.

Here, the authors characterize the structural organization and condensate behavior of the microtubule plus-end tracking protein Bik1, employing SAXS, computational modeling, microscopy, and crosslinking mass spectrometry.

The inner surface of the heart has a meshwork of muscles called trabeculae. McGurk et al. report the genetic regulation of these complex structures across common and rare variants, revealing pathways implicated in heart development and cell fate.

For presymptomatic infants at risk for SMA type 1, onasemnogene abeparvovec improves motor outcomes, ventilator-free survival, and nutritional/respiratory independence compared with untreated or treated symptomatic patients

In a first-in-human trial of a triple combination of broadly neutralizing antibodies in people living with HIV, 83% of participants maintained virologic suppression for the duration of antibody therapy, with 42% showing virologic suppression for at least 38–44 weeks, despite the decline of serum antibody concentrations to low or undetectable levels.

Thermal contraction effect increases with time dominates the long-term deformation trend of the Heber geothermal field, while pressure effects of pressure fluctuation and poroelastic responses keep relatively stable and drive short-term changes.

The primary visual cortex (V1) carries signals related to visual speed, and its responses are also affected by run speed. Here the authors report that nearly half of the V1 neurons were reliably driven by combinations of visual speed and run speed. As a population, V1 neurons predicted a linear combination of visual and run speed better than visual or run speeds alone.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Here, the authors expand knowledge of the genetic architecture of age-related cataracts, exploring associated pathways and drug-gene interactions, and clarify the roles of type 1 diabetes and UV exposure in cataract etiology.

Leydig cells are essential for male sexual development, but their developmental origins are not fully established. Here, authors map early developmental stages of fetal Leydig cells in mice, revealing critical genetic factors that guide their maturation and function.

Sekar Kathiresan et al. report genome-wide association studies for polygenic dyslipidemia. From a meta-analysis of seven genome-wide association studies and follow-up in five replication studies, they identify 11 new genetic associations for LDL cholesterol, HDL cholesterol and triglycerides.

This study uses data assimilation to reconstruct the Southern Annular Mode over the last 2000 years. The authors find that the mode’s history reflects natural climate variability, except for the most-recent positive trend

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

Genome-wide association studies (GWAS) have identified hundreds of genomic risk regions for prostate cancer. Here, the authors perform a transcriptome wide association study (TWAS) by incorporating prostate cancer GWAS with gene expression data to identify potential novel prostate cancer risk loci and possible risk mechanisms.

Authors carry out a genomic analysis of carbapenem-resistant Klebsiella pneumoniae bloodstream isolates, noting subclonal expansion, associated with the emergence of a hypervirulent subpopulation.

Compressed Perturb-seq incorporates compressed sensing to genetic screening for scalable discovery of genetic interactions.

The crystal structure of the heterodimeric transcriptional regulator GABPα/β bound to DNA reveals extensive protein–protein interactions between an ETS domain and ankyrin repeats that may influence DNA binding affinity.

A discovery pipeline integrating time-resolved HT-SAXS and fragment screening identifies chemical leads targeting exemplary allosteric states of mitochondrial oxidoreductase apoptosis-inducing factor (AIF).

Evan Eichler and colleagues identify a recurrent microdeletion on 16p12.1 associated with developmental, cognitive and neuropsychiatric phenotypes. They also show that more severe phenotypes are frequently correlated with the presence of a second large genomic rearrangement, supporting a complex model of pathogenesis that may underlie the variable expressivity typical of many microdeletion syndromes.

The design and mutagenesis of an α-helix-containing monomeric miniprotein, PPα-Tyr, provide insights into weak noncovalent CH–π interactions that help define and stabilize folded proteins and protein–ligand interactions.

In this study, the authors show that the mouse ortholog of the amyotropic lateral sclerosis/frontotemporal dementia (ALS/FTD)-associated human locus C9ORF72 exhibits highly enriched expression in the neuronal cell types that show susceptibility during the disease. These findings suggest a potential explanation for the cell selectivity observed in ALS/FTD.

TCAT is a pipeline that can simultaneously capture gene expression programs related to T cell subsets and activation states for accurate T cell characterization.

O’Regan and colleagues use deep-learning cardiac motion analysis in participants of the UK Biobank to measure diastolic functional traits and perform a genome-wide association study to generate insights into the genetic and environmental factors that influence diastolic function.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Computational analyses integrating whole-genome sequencing, cardiac epigenomic data and RNA-binding-protein data identify a role for noncoding de novo mutations in congenital heart disease.

The human RBR E3 ligase Parkin is captured in complex with phosphoubiquitin, revealing a cryptic ubiquitin-binding site and indicating a mechanism of cooperation between RBR modules for activation.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Distinct monocyte subsets associate with different outcomes of SIV vaccines.

John Perry and colleagues report the results of a large genome-wide association study meta-analysis to identify variants influencing age at natural menopause. They identify 54 independent signals and find enrichment near genes involved in delayed puberty and DNA damage response.

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt βII-spectrin function and disturb cytoskeletal organization and dynamics.

Memory lapses can occur due to ineffective encoding, but it is unclear if targeted brain stimulation can improve memory performance. Here, authors use a closed-loop system to decode and stimulate periods of ineffective encoding, showing that stimulation of lateral temporal cortex can enhance memory.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

RNA localization is mediated by kinesin motors and anchoring. However, mechanisms underlying specificity are unclear. Here, the authors find that MBNL protein’s zinc fingers prefer specific kinesins, and its unstructured tail mediates membrane anchoring.

Genome-wide analyses of vaccine antibody responses in 2,499 infants from Uganda, South Africa and Burkina Faso identify associations between specific HLA genes and response to eight vaccines, providing insights that could be considered for population-adjusted vaccine design strategies.

Activated B cells and T cells accumulate within joints of patients with rheumatoid arthritis. Here, the authors use single-cell transcriptome and repertoire profiling to identify clonally expanded synovial B cells and T cells and define their phenotypes and predicted cell-cell interactions.

Human cytomegalovirus (CMV) infects a wide range of host cells. Here, using a high throughput antibody screening platform, the authors identify the cell surface receptor CD46 to be required for CMV infection of epithelial cells and trophoblast-derived cells, the latter critical for congenital CMV infection.

Genomic analysis of Mycobacterium tuberculosis (Mtb) isolated from tuberculosis patients identifies the transmission dynamics of Mtb in Vietnam including frequent transmission of Beijing lineage and positive selection for EsxW Beijing variant.

Distant metastases from pancreatic cancer patients were previously reported by the authors to be dependent on the glucose-metabolizing enzyme phosphogluconate dehydrogenase (PGD). Here the authors report a novel metabolic adaptation that that stably activates PGD to reprogram metastatic chromatin.

Sexual reproduction in eukaryotes involves gamete fusion, mediated by fusogenic proteins. Here, the authors identify fusogenic protein homologs encoded within mobile genetic elements in archaeal genomes, solve the crystal structure of one of the proteins, and show that its ectopic expression can fuse mammalian cells, suggesting potential roles in cell-cell fusion and gene exchange.

An integrative framework to simultaneously interrogate the dynamics of the transcriptome and proteome at subcellular resolution that combines two methods, localization of RNA (LoRNA) and a streamlined density-based localization of proteins by isotope tagging (dLOPIT).

Large-scale screens of chemical and genetic vulnerabilities in cancer are typically limited to simple readouts of cell viability. Here, the authors develop a method for profiling post-perturbation transcriptional responses across large pools of cancer cell lines, enabling deep characterization of shared and context-specific responses.

Genome-wide data from ancient and modern individuals in Remote Oceania indicate population replacement but language continuity over the past 2,500 years. Papuan migrations led to almost complete genetic replacement of in situ East Asian-derived populations, but not replacement of Austronesian languages.

Identification of response biomarkers is a key step towards the development of personalised care. Here, Jayson et al. identify plasma Tie2 as a biomarker for the response of the tumor vasculature to anti-angiogenics in patients with metastatic colorectal cancer, suggesting that monitoring Tie2 levels may help guide therapy in the clinics.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

For infants with three copies of SMN1 at risk for spinal muscular atrophy (SMA) type 1, onasemnogene abeparvovec improves ventilator-free survival and nutritional/respiratory independence and allows motor development indistinguishable from healthy children without SMA.

The chromatin-remodelling enzyme ATRX and the transcription factor HNF4A are identified as pivotal regulators of colonic epithelial identity, with roles in metastasis in colorectal cancer.

Methods to produce haplotype-resolved genome assemblies often rely on access to family trios. The authors present FALCON-Phase, a tool that combines ultra-long range Hi-C chromatin interaction data with a long read de novo assembly to extend haplotype phasing to the contig or scaffold level.

The role of keratinocyte subpopulations in the different phases of the viral cycle during HPV16 infection remains to be characterised. Here, single cell RNA sequencing of HPV16 infected and uninfected organoids identifies 12 distinct keratinocyte populations including an HPV-reprogrammed keratinocyte subpopulation that is linked to cancer.