Search

Climate warming increases evapotranspiration (ET) more in boreal peatlands than in forests. Observations show that peatland ET can exceed forest ET by up to 30%, indicating a stronger warming response in peatlands. Earth system models do not fully account for peatlands and hence may underestimate future boreal ET.

Nelson Freimer and colleagues analyze gene expression data from multiple tissue samples combined with genotype data from vervet monkeys to catalog expression quantitative trait loci (eQTLs). They generate a transcriptome resource analogous to the GTEx project and perform comparative and eQTL enrichment analyses for various traits.

New evidence identifies γδ T cells as key players in both epithelial defense and the regulation of innate and acquired immune responses.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

Tumour-infiltrating lymphocytes (TILs) can be suppressed by the tumour, but how this occurs is not clear. Here the authors show that the miR-200 family, which suppresses epithelial–mesenchymal transition, also targets tumour cell PD-L1 and thereby intratumoral immunosuppression and metastasis.

Two de novo designed protein classes that link phosphorylation by tyrosine and serine kinases to protein-protein association provide potential new avenues to regulating cell function.

The results of scientific studies should be accompanied by information that individuals can use to make uncertainty judgements. By including this information, we might increase trust in the scientific process. We advocate for scientists to use quantitative uncertainty informative data to provide this information when reporting results.

This study uses zinc-finger nucleases to target an inducible XIST transgene into chromosome 21 from trisomic Down’s syndrome pluripotent stem cells; the XIST RNA coats one copy of chromosome 21 and triggers whole chromosome silencing, suggesting the potential of this approach for studying chromosomal disorders such as Down’s syndrome and for research into gene therapies.

A versatile electrokinetic trap overcomes rotational and translational Brownian motion for simultaneously controlling the two-dimensional position with a precision of up to 20 nm and 0.5° in the three-dimensional angle of an untethered nanowire under an optical microscope.

The mechanism of U6 small nuclear ribonucleoprotein (snRNP) biogenesis is not well understood. Here the authors characterize the enzymatic activities and structures of yeast and human U6 RNA processing enzyme Usb1, reconstitute post-transcriptional assembly of yeast U6 snRNP in vitro, and propose a model for U6 snRNP assembly.

Many patients fail to respond to T cell based immunotherapies. Here, the authors, through a high-throughput screening, identify HSP90 inhibitors as a class of preferred drugs for treatment combination with immunotherapy.

A wealth of gene expression data is publicly available, yet is little use without additional human curation. Ma’ayan and colleagues report a crowdsourcing project involving over 70 participants to annotate and analyse thousands of human disease-related gene expression datasets.

An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits.

Prediction of genetic values using whole-genome markers has been successfully applied in commercial breeding. This article outlines the use of this method for predicting health-related outcomes in humans.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

Results from a phase 1 clinical trial show that a broadly neutralizing, HIV-specific antibody is durably expressed in vivo from a viral vector, highlighting an alternate approach for the delivery of antibodies in humans.

The liver is an important regulator of glucose homeostasis. Here, the authors provide insight into the molecular signalling pathways controlling hepatic gluconeogenesis by showing that SIK protein kinases suppress gluconeogenesis, and that glucagon—but not insulin—regulates phosphorylation of SIK2.

Stuart Cook and colleagues study the role of TTN (titin)-truncating variants using a combination of heart physiology experiments in rats and genomic analysis in humans. Their data show that TTN variants are associated with a range of cardiac phenotypes in healthy individuals and in patients with dilated cardiomyopathy.

DNA methylation in the brain is a dynamic process, but gene-specific regulation of this process is poorly understood. Here, Day and colleagues show that extra-coding RNAs interact with DNA methyltransferases and regulate neuronal DNA methylation to control gene expression in locus-specific manner in neurons.

Here, the authors show that real-world extraordinary altruists, including heroic rescuers and altruistic kidney donors, are distinguished by unusually unselfish traits and decision-making patterns. This pattern was not predicted by a general sample of adults who were asked what traits would characterize altruists.

Parkinson’s disease (PD) is a common neurodegenerative disorder with a complex etiology involving genetics and the environment. Here, Vallerga et al. identify two CpG probes associated with PD in a blood cell type-corrected epigenome-wide meta-analysis, implicating the SLC7A11 gene as a plausible biological target.

Proteomic analysis of cerebrospinal fluid from individuals with autosomal dominant Alzheimer’s disease reveals how this complex and chronic disease evolves over many decades.

Bensinger and colleagues show that interferons promote host cell resistance to bacterial cytolysins by decreasing cholesterol synthesis and promoting the esterification of cholesterol, which alters the availability of this pool of ‘free’ cholesterol needed for pore formation.

Iron is essential during pregnancy for embryo and placental development and maternal health. However, in this study using mouse models, the authors demonstrate that excess maternal iron causes adverse embryo outcomes in pregnancies with underlying systemic inflammation.

Here, the authors show that SARS-CoV-2 infection causes gut microbiome dysbiosis and gut epithelial cell alterations in a mouse model, and correlate dysbiosis observed in COVID-19 patients with blood stream infections, matching reads of bacterial sequences from stool samples to organisms found in the blood.

Quantum dots with different size emit light at different wavelengths but also different brightness, which complicates analysis of fluorescence images. Here, the authors synthesize multicolour brightness-equalized quantum dots by controlling the composition and structure of core-shell HgCdSeS-CdZnS nanocrystals.

High arousal enables young people to better detect salient stimuli. In older people, arousal leads to increased processing of all stimuli. This difference can be explained by age-related changes in how the locus coeruleus–noradrenaline system interacts with cortical attention networks.

Altered epigenetics is a feature of cancer but whether these changes occur early in tumour development is unclear. Here, the authors analyse methylation events in breast cancer and adjacent normal pairs, and show that methylation changes in the normal tissue are also found in the tumour, suggesting that some of these events occur early in cancer.

Malignant phenotypes in the mammary epithelium have been correlated to increases in extracellular matrix stiffness. It is now shown that the effect of matrix stiffness in normal mammary epithelial cells can be offset by an increase in basement-membrane ligands and that both the stiffness and composition of the matrix are sensed by the β4 integrin. The results suggest that the relationship between matrix stiffness and composition is a more relevant predictor of breast-cancer progression.

Perceiving objects as lifelike is an inferential process but whether it occurs quickly and how it applies to groups of objects is not well understood. Here the authors show that observers’ percepts of crowd lifelikeness are fast and represent the average of the individual objects comprising that crowd.

The performance of large language models (LLMs) is often compared to human performance on decision-making tasks. In this Review, Brady and colleagues examine LLM outputs through the lens of dual-process theory, considering the hallmarks of System 1 and System 2 human decision-making.

This study has developed the first small molecule NEDD8-activating enzyme (NAE) inhibitor, which induces cancer cell death and exerts anti-tumour activity in preclinical mouse models. This work establishes NAE as an anti-cancer target and may lead to new anti-cancer therapeutics.

Wnt receptor levels drive signaling. Here the authors find that precise signaling in the Wnt morphogen gradient relies on Usp46, a deubiquitylase that enhances target cells sensitivity by increasing cell surface levels of the Wnt receptor Arrow/LRP6.

The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

Chemically inducible protein dimerization serves as a useful tool to investigate biological systems and construct synthetic circuits. Optimization of a protein-protein interaction dependent on the plant hormone gibberellin yields a portable dimerization system that can be combined with rapamycin to assemble logic gates.

The authors used deep learning to derive a biological clock based on routine blood markers in mice that distinguishes slow-aging from fast-aging animals. Drawing on data from the NIH Study of Longitudinal Aging in Mice and a study of aging at The Jackson Laboratory, this clock reveals that platelets are key in predicting biological age.

Rapid extracellular antigen profiling of a cohort of 194 individuals infected with SARS-CoV-2 uncovers diverse autoantibody responses that affect COVID-19 disease severity, progression and clinical and immunological characteristics.

The LITMUS consortium provides a resource of rodent MASLD models benchmarked against metabolic, histologic and transcriptomic features that are relevant for human MASLD. The work is useful for selecting relevant rodent models for studying this common disease.

Aging is associated with various changes in the brain, including transcription alteration. Here, Bradshaw and colleagues describe the transcriptome of aged human cortical microglia, and show age-related gene expression as related to neurodegeneration.

In a retrospective analysis of patients with Lynch syndrome and primary cancers treated with immune checkpoint inhibitors, 12% developed subsequent malignancies, suggesting that this treatment may not eliminate risk in individuals predisposed to mismatch repair-deficient cancers, and ongoing surveillance is warranted.