Search

In a phase 1 trial testing healthy donor fecal microbial transplantation with immune checkpoint blockade in patients with previously untreated renal cell carcinoma, treatment was safe with an encouraging response signal and microbiome analyses, suggesting specific donor taxa associations with toxicity.

This multicenter study demonstrates use of dried and capillary blood as a minimally invasive, scalable approach for Alzheimer’s biomarker testing in research, with potential as a widely scalable population-based research approach, especially in resource-limited settings.

Differential isoform usage is identified with high statistical power from spatial transcriptomics data.

Here the authors show that gut metagenomes of Indigenous Australian infants living remotely, display greater diversity and abundance of bacteria, viruses and fungi, compared to non-Indigenous infants living in urban Australia, suggesting that while having access to Western foods, the infants start life with a gut microbiome that retains key features of pre-industrialized societies.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

PU.1^low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunotherapeutic approaches for treatment.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Detecting dilute airborne biomarkers is important in healthcare but is limited by the low sensitivity of current gas sensors. A portable, low-cost device is introduced that uses water condensation to enrich airborne biomarkers into a concentrated liquid, enabling existing liquid sensors to detect biomarkers with high sensitivity and broad accessibility.

Shaw et al identify the neonatal Fc receptor (FcRn) as a host factor required for infection of cells by several divergent arteriviruses, and demonstrate that anti-FcRn antibodies can be used to block arterivirus infection.

SEEKR is a method that deconstructs linear sequence relationships between lncRNAs and evaluates similarity on the basis of abundance of short motifs called k-mers. LncRNAs of related function often have similar k-mer profiles despite lacking linear homology.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

While learning a typing task, epilepsy patients show higher hippocampal ripple rates during brief rest breaks than while typing. These ‘offline’ ripples predict gains in speed, suggesting that ripples contribute to motor learning during wakeful rest.

A streamlined sequencing process enables identification of disease-causing variants in the clinic within 8 hours.

Here the authors show that rehabilitating nuclear speckles, membraneless organelles involved in mRNA processing and gene regulation, can boost protein quality control and reduce toxic protein buildup, as well as ameliorate models of diseases like tauopathy and retinal degeneration.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

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.

There is increasing evidence of a functional interaction between acute myeloid leukemia (AML) and immune cells, influencing disease outcome. Here the authors study how distinct oncogenes differentially affect the host immune response to leukemic cells in preclinical models of AML.

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.

The archaeological site Shinfa-Metema 1 in the lowlands of northwest Ethiopia provides early evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow.

The transmission spectrum of the exoplanet WASP-39b is obtained using observations from the Single-Object Slitless Spectroscopy mode of the Near Infrared Imager and Slitless Spectrograph instrument aboard the JWST.

Here the authors use positron emission tomography to visualize fibroblasts in patients with arthritis and combined with spatial transcriptomic data show that these cells undergo a phenotypic shift upon resolution of inflammation. A CD200⁺DKK3⁺ fibroblast subset promotes this resolution by inhibiting tumor necrosis factor and interleukin-17A.

HIV envelope is a target for vaccine development, but induction of broadly neutralizing antibodies has been difficult. Here, the authors show that electroporation with a synthetic DNA vaccine construct allows in vivo production of HIV envelope native like trimers to induce autologous tier-2 neutralizing antibodies targeting a C3/V5 epitope in mice.

Parhizkar et al. show that lemborexant, an orexin receptor antagonist, protects against neurodegeneration in male tau transgenic mice by preventing tau protein build-up and inflammation, highlighting its potential for preventing neurodegeneration.

Analysis of shared chromosomal segments is applied to identify distantly related, previously undiagnosed carriers of a rare KCNE1 variant. The carriers are shown to have the Long QT Syndrome phenotype with incomplete penetrance.

Cas9 is a powerful genome-manipulation enzyme, although how its catalytic activity is controlled is not completely solved. Now, cryo-electron microscopy structures of Acidothermus cellulolyticus Cas9 provide atomic-level insights into its activation involving DNA binding, conformational changes and the formation of its two active sites.

Sex differences in a mouse model of synucleinopathy reveals female resilience to disease progression despite early brain pathology, contrasting with accelerated disease in male mice after alpha-synuclein preformed fibril injection.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

A brain-imaging study in humans demonstrates that older age brain network decline varies in relation to an individual’s education and predicts future dementia severity beyond other markers of Alzheimer’s disease-related genetic risk and pathology.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

It is not clear to what degree activity in dorsal premotor cortex (PMd) reflects perceptual-deliberation versus action-selection aspects of decision-making. Here, the authors report that monkey PMd neurons do not express correlates of the perceptual decision independently of the action choices.

Ader et al. find a grommet-like role for ESCRTs distinct from their nuclear envelope sealing function after spindle pole body extrusion. The grommet works with spindle pole body components that establish a diffusion barrier to maintain compartmentalization.

Ticks inject evasins at the bite site to bind multiple redundant chemokines and inhibit inflammation allowing blood feeding. Here, the authors identify evasin derived short peptides with broad spectrum anti-chemokine activity that could be used to develop new treatments for inflammatory disease.

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.

MKL1 is a key transcriptional co-activator of actin cytoskeleton genes. Here the authors show that MKL1 activation in somatic cells reduces chromatin accessibility and hinders full reprogramming to pluripotency. Reduction of MKL1, disruption of actin cytoskeleton and its links to the nucleus relieve this repression.

The authors present the largest genome-wide association study to date for a rare Parkinsonian disorder, progressive supranuclear palsy (PSP). They include follow-up investigations of the identified susceptibility loci, functional consequences, and cell-specific pathologies, providing insights into genetic and molecular mechanisms underlying PSP.

SpaGFT is a spatial omics representation method. It identifies spatially variable genes, enhances gene imputation, detects immunological regions, and characterises variations in secondary lymphoid organs. This method improves predictive power in wide downstream machine-learning tasks.

The response of prostate cancer cells to androgens depends on the dose. Here, the authors show that low levels of androgens function through androgen receptor (AR) monomers to activate mTOR and promote cell proliferation, while high dose androgens induce AR dimerization to inhibit c-MYC expression and facilitate cell differentiation.

A multiomics single-cell atlas of the human maternal–fetal interface including the myometrium, combining spatial transcriptomics data with chromatin accessibility, provides a comprehensive analysis of cell states as placental cells infiltrate the uterus during early pregnancy.

Mouse models often combine mutant alleles to accelerate cancer development, limiting oncogenic diversity. Here the authors show that sporadic MYC activation in Vk*MYC mice is sufficient to induce tumors with a variety of secondary mutations that mirror the genetic heterogeneity of human myeloma.

The Atr-Check1 pathway is involved in cell cycle and the DNA damage response. Here, the authors show that the Atr-Check1 pathway can inhibit axon regeneration in response to Piezo-mediated mechanosensation, affecting functional recovery.

Derivation of human primordial germ cell-like cells (hPGCLCs) is critical for reproductive medicine. Here, authors report the induction of hPGCLCs in a bioengineered human pluripotent stem cell culture that mimics peri-implantation human development.

Optimizing study design is critical for increasing standardized effect sizes and replicability, and the features that increase replicability in cross-sectional and longitudinal brain-wide association studies are explored.

Amyloid-like proteins are central to age-related diseases, such as Alzheimer’s and Parkinson’s. Here, the authors show that transcription errors can produce mutant proteins with enhanced amyloid- and prion-like properties in human cells.