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Oxytocin promotes social behaviors, but its cortical targets remain unclear. Here, authors show that oxytocin activates local interneurons in the rat prefrontal cortex, enhancing sociability through top-down control of the basolateral amygdala.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Zinc is an essential micronutrient for plants, however its excess causes cellular damage. Here, the authors report that natural variation of Trichome Birefringence (TBR) gene confers zinc toxicity tolerance through modulating root cell wall pectin methylesterification in Arabidopsis.

Deep brain stimulation tuned to cue-reactivity within the nucleus accumbens region reduced drug cravings, heralding an evocation-based programming strategy for opioid use disorder.

The presence of EGFR mutations and de novo MET aberrations limited response to EGFR inhibitors in patients with advance non-small cell lung cancer (NSCLC). Here, the authors report a phase 2 randomised clinical trial investigating first-line osimertinib (EGFR inhibitor) plus savolitinib (c-MET inhibitor) in patients with MET-aberrant, EGFR-mutant advanced NSCLC.

How the complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth is explored.

Möhring et al. assess the expected effects of a global transformation of agricultural pest management. They find positive contributions to multiple sustainability challenges, assess drivers and discuss necessary steps for a transformation.

Vaginal birth, exclusive breastfeeding and early contact with siblings promote colonization of the infant gut with bifidobacteria capable of producing aromatic lactates, a microbial and metabolite signal that is inversely related to the risk of allergen-specific sensitization and dermatitis later in life.

Research in the tropics is unevenly distributed across regions and biomes. Here, the authors find that moist broadleaf forests account for 73% of all tropical citations but cover 29% of the land area, while drier, climate-vulnerable areas with fewer trees remain under-sampled and under-cited.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Understanding the growth dynamics of GBMs can help expand therapeutic options. Here, authors use a cross-species computational approach to compare GBM cells to healthy neural stem cells, identifying predictors and modulators of tumour growth, including the Wnt antagonist, SFRP1, which stalls growth in preclinical xenograft models.

The neural mechanisms driving seizure development in peritumoral brain regions remain incompletely defined. Here, using patient tissue, glioma mouse model, and computational simulation, the authors identify early pathological activities that are predictive of tumor-associated seizures.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Consensus exists on the urgent need for food systems to be more sustainable, but defining their environmentally safe operating space is challenging. This study proposes food system boundaries as a share of planetary boundaries, defining budgets across nine boundaries and revealing where boundary transgression is most critical.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Pretrained on SpatialCorpus-110M, a curated resource of vast and diverse transcriptomes of dissociated and spatially resolved cells from both human and mouse, Nicheformer advances toward building foundation models for spatial single-cell analysis.

We can often observe only a small fraction of a system, which leads to biases in the inference of its global properties. Here, the authors develop a framework that enables overcoming subsampling effects, apply it to recordings from developing neural networks, and find that neural networks become critical as they mature.

Single crystal X-ray diffraction is an invaluable tool for molecular structure determination, but growing single crystals is often an arduous process. Here the authors find that the structures of a wide array of molecules can be determined by SCXRD when included in hydrogen-bonded guanidinium organosulfonate host frameworks in a single-step crystallization.

By learning a differentiation potential using an optimal transport-based approach, STORIES models and infers cell fate trajectories using spatiotemporal omics data.

Exome sequencing of 851 trios from more than 2,500 individuals finds 187 genes with de novo mutations that contribute to meningomyelocele (spina bifida) and highlights critical pathways required for neural tube closure.

A millimetre-scale bioresorbable optoelectronic system with an onboard power supply and a wireless, optical control mechanism is developed for general applications in electrotherapy and specific uses in temporary cardiac pacing.

Understanding human preimplantation development is invaluable for human reproduction and stem cell research. By employing single-cell RNA sequencing in oocytes, zygotes and single blastomeres, Töhönen et al.identify new regulatory factors and sequences that drive early human preimplantation development.

Transcriptional cell states can drive treatment resistance in cancer. Here, the authors develop ReSisTrace to predict cell states that are primed to resist ovarian cancer treatment and validate their findings using small molecule inhibitors.

This work presents scEpi²-seq, a method for simultaneous single-cell profiling of DNA methylation and histone modifications, enabling direct investigation of the interplay between these two epigenomic marks.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

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.

Alison Dunning, Stacey Edwards and colleagues analyze 3,872 common variants across the ESR1 locus in 118,816 women. They find five independent variants within regulatory regions that associate with different breast cancer–related phenotypes and regulate the expression of ESR1, RMND1 and CCDC170.

Random segregation of extrachromosomal DNA contributes to intratumoral heterogeneity and facilitates the rapid adaptation of human tumor cells to anticancer drugs.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

In this genomic analysis of peripheral blood samples of the phase 3 CheckMate-067 trial of ipilimumab (IPI) versus nivolumab (NIVO) versus ipilimumab and nivolumab (IPI-NIVO) in melanoma, the status of certain mitochondrial haplogroups in patients was associated therapeutic resistance to NIVO or IPI-NIVO, a finding validated in an independent cohort.

Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.

A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.

BRCA-deficient breast cancer is characterised by homologous recombination deficiency. Here, the authors show that hypermethylated BRCA1 phenotypically copies mutated BRCA1 in triple negative breast cancers.

To survive and evade host responses, malaria parasites export several hundred proteins into the host cell on infection. A feature of these proteins is a conserved, pentameric motif that is cleaved by an unknown protease before export. This is one of two independent studies revealing the identity of the protease as plasmepsin V, an aspartic acid protease located in the endoplasmic reticulum. This enzyme is essential for parasite viability and is an attractive candidate for drug development.

Direct interaction between the small GTPase Rab7a and the cation channel TPC2 has been reported but the functional regulation is less clear. Here, the authors show that Rab7a enhances the activity of TPC2 to promote melanoma progression through the GSK3β/β-Catenin/MITF axis.

A series of genetic studies have led to the discovery of novel independent loci and candidate genes associated with red blood cell phenotype; for a proportion of these genes potential single-nucleotide genetic variants are also identified, providing new insights into genetic pathways controlling red blood cell formation, function and pathology.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.