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The posterolateral cortical amygdala and other connected brain regions have a key role in mediating the transition from investigative to aggressive behaviour in male mice.

Aspartoacylase expression in white adipose tissue regulates circulating levels of N-acetylaspartate, which in turn modulates plasma pyrimidine levels and regulates postprandial body temperature.

Massively parallel DNA sequencing allows entire genomes to be screened for genetic changes associated with tumour progression. Here, the genomes of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer were analysed. The samples came from peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The findings indicate that cells with a distinct subset of the primary tumour mutation might be selected during metastasis and xenografting.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

This Resource describes data, code and tools developed for the Human Reference Atlas and the Human BioMolecular Atlas Program for building and navigating a multiscale human atlas.

The binding of angiopoietin-like proteins to immune-inhibitory receptors maintains ‘stemness’ of haematopoietic stem cells and supports leukaemia development.

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.

Multi-ancestry genome-wide association meta-analysis of major depression identifies new risk loci, assesses the transferability of risk loci across ancestry groups, and improves fine-mapping resolution and prioritization of candidate effector genes.

Different pairs of antibiotics show qualitatively different bacterial clearance interactions—some pairs show reciprocal suppression whereby the drug mixture efficacy is weaker than the individual drugs alone, and the clearance efficacy decreases as more drugs are added.

In the homologous recombination repair-deficient population of TALAPRO-2, a placebo-controlled phase 3 trial, treatment of patients with metastatic castration-resistant prostate cancer with the poly(ADP-ribose) polymerase inhibitor talazoparib plus enzalutamide led to prolonged progression-free survival compared with placebo plus enzalutamide.

Readout of a superconducting qubit embedded in a circuit quantum electrodynamics architecture is demonstrated at optical frequencies through a low-noise electro-optomechanical transducer.

Here, the authors integrate genomic, proteomic, and phenotypic data from UK Biobank, identifying over 1,100 gene-environment interactions. They catalogue interactions between 101 blood proteins and 153 exposures, which may refine biomarker discovery.

Seder and colleagues show that mucosal adenoviral-vectored vaccine boosting durably prevents infection in nonhuman primates of the highly transmissible, heterologous XBB.1.16 strain of SARS-CoV-2.

Precise lymphoid tissue architecture is needed to generate adaptive immune responses. Brink and colleagues show that CD4⁺ DCs express the chemotactic receptor EBI2, which is required for their splenic positioning and capture of particulate blood-borne antigens.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

MEF2C is a transcription factor required for B-cell proliferation. Here the authors show that MEF2C is also needed in B-cell development and recovery from stress by inducing expression of DNA repair factors that prevent double stranded breaks and enable VDJ recombination.

High-quality genome assemblies of four Solanum Americanum accessions lead to the identification of three NLR-encoding genes, Rpi-amr4, R02860 and R04373, that recognize potato late blight pathogen Phytophthora infestans effectors.

Wang et al. reveal a noncanonical mechanism for EZH2 in binding the oncoprotein cMyc to promote tumorigenesis, and develop a small-molecule degrader, MS177, to target both canonical and noncanonical functions of EZH2 to suppress tumour growth.

The identification of biomarkers of response to PARP inhibitors can enable selection of appropriate ovarian cancer patients for treatment. In this study, the authors report clinical results and exploratory biomarker analyses from the ARIEL2 phase 2 clinical trial on the safety and efficacy of the PARP inhibitor rucaparib in patients with recurrent ovarian cancers

Interferon-gamma (IFN-γ) is an important but not exclusive proinflammatory mediator in macrophages. Here authors show that IFN-γ-independent macrophage autoactivation involves endoplasmic reticulum (ER) stress which in turn induces the GTP-binding protein Septin2 to limit inflammation via a negative feedback loop.

Current methods for acquiring dissemination kinetics of rare circulating tumor cells (CTCs) that form metastases have several limitations. Here, the authors show an approach for measuring endogenous CTC kinetics by continuously exchanging CTC-containing blood between un-anesthetized, tumor-bearing mice and healthy, tumor-free counterparts.

The Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types; these data were compared with those from human to confirm substantial conservation in the newly annotated potential functional sequences and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

Tree spatial data, spatial statistics and dynamical theory reveal the relationship between spatial patterns and population-level interaction coefficients and their consequences for multispecies dynamics and coexistence.

He et al. develop a network-based metric of amyloid-β burden by integrating individualized brain connectomes with amyloid-PET imaging. This approach improves prediction of future cognitive decline in older adults and may support earlier identification of individuals at risk of dementia.

A luteinizing hormone–releasing hormone antagonist, used clinically for sex-steroid inhibition, promotes quiescence of hematopoietic stem cells and thereby promotes hematopoietic recovery and survival of lethally irradiated mice.

Clinical and genetic phenotyping of consanguineous family cases of neonatal syndromic diabetes and type 2 diabetes, combined with in-depth functional studies in pluripotent stem cells, reveals a role for genetic variants of ONECUT1 in monogenic and multifactorial diabetes.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

In this study, the authors show that a subset of cerebellar granule neurons originate not from the granule neuron precursors (GNPs) but from a population of Nestin-expressing progenitors (NEPs) in the deep external germinal layer. In addition, they find that these NEPs are more susceptible to Sonic Hedgehog–induced genomic instability and tumor formation.

PGC-1α is a master regulator activating the transcription of key genes controlling the cell’s energy production. Here the authors show that PGC-1α has a function in the NXF1-dependent nuclear export of mRNAs.

Reimer et al. used cryo-EM and cellular assays to reveal the structural and regulatory features that distinguish LRRK1 from LRRK2, and placed these features in the context of the evolution of the LRRK family of proteins.

Rubisco is a complex, ubiquitous protein composed of eight large and eight small subunits. By assembling Rubisco in bacterial cells, the specific characteristics of individual small subunits have been investigated with a view to engineering more efficient carbon fixation.

External cycling regenerates nitrogen oxides from the NO_x oxidative reservoir, NO_z. Aircraft observations reveal NO_x external cycling compensates for NO_x aging, sustaining NO_x distribution and production of OH radicals far from NO_x emission sources

Stapled α-helical peptides are promising for targeting challenging targets such as transcription factors, but achieving sufficient cell permeability while avoiding off-target cleavage is difficult. Here, the authors present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects based on comprehensive investigations of their properties.

Fine silicate dust generated by the Chicxulub impact had a dominant role in the global cooling and disruption of photosynthesis that followed, according to palaeoclimate simulations constrained by grain-size analysis of Cretaceous-Palaeogene boundary sediments.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Many genetic variants have been associated with human traits, but the mechanism is often unknown. Here, the authors integrate local and distal genetic associations with multi-omics datasets to provide a roadmap to understand the underlying mechanisms of GWAS variants on complex traits.

PTSD has been associated with DNA methylation of specific loci in the genome, but studies have been limited by small sample sizes. Here, the authors perform a meta-analysis of DNA methylation data from 10 different cohorts and identify CpGs in AHRR that are associated with PTSD.

Targeted mass spectrometry enables reproducible and accurate lipid quantification but dedicated software tools to develop targeted lipidomics assays are lacking. Here, the authors develop a targeted lipidomics workbench and lipid knowledgebase for the streamlined generation of targeted assays.

Spur-type of growth is preferred for apple production. Here, the authors employ the trio-based phasing approach to assemble a fully phased Fuji genome and reveal the association of a 167-bp deletion in the promoter region of the MdTCP11 gene with the spur-type varieties.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.

FLT3 is commonly mutated in acute myeloid leukaemia and treatment with FLT3 inhibitors often ends with relapse. Here, the authors perform exome sequencing of samples from patients treated with the FLT3 inhibitor, crenolanib, to show that resistance occurs due to diverse molecular mechanisms, not primarily due to secondary FLT3 mutations.

High levels of extended spectrum beta-lactamase (ESBL) and carbapenemase encoding genes were detected in bacterial isolates causing neonatal sepsis in LMICs. Authors assess the in vitro activity of three antibiotics (fosfomycin, flomoxef and amikacin) in combination against ESBL-producing Klebsiella pneumoniae and Escherichia coli isolates.