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Single atom catalysts, comprising minute amounts of transition metals dispersed on inert substrates, have emerged as prominent materials in heterogenous catalysis but their precise arrangement on surfaces is challenging. Here, the authors introduce the on-surface synthesis of a single atom platform wherein atoms are firmly anchored to specific coordination sites evenly distributed along carbon-based polymers.

Mutations in elongation factor G protect bacteria from aminoglycoside antibiotics through unknown mechanisms. Here, the authors show that the mutations selectively slow the movement of antibiotic-bound ribosomes along mRNA, which prevents error-prone protein synthesis and thus membrane damage and antibiotic uptake.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Recent studies have traced haematopoiesis at the clonal level but lack a way to extract dynamical information. Here, authors develop CLADES, a tool to estimate cellular kinetics and the number of divisions to produce mature cells for each clone, in human cord blood and adult mouse haematopoiesis.

Trypanosomes evade the immune response through antigenic variation of a surface coat containing variant surface glycoproteins (VSG). They also express invariant surface glycoproteins (ISGs), which are less well understood. Here, Macleod et al. show that ISG65 of T. brucei is a receptor for complement component 3. They provide the crystal structure of T. brucei ISG65 in complex with complement C3d and show evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance in vivo.

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.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

During pregnancy, maternal cells are transferred to the fetus, where they can reach the developing brain. In this study, the authors demonstrate that these maternal cells play an important role in neurodevelopment.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

The identification of two cryptic species of the fungal pathogen that causes white-nose disease in bats highlights the need to integrate studies of genetic variability in pathogens into disease surveillance, management and prevention strategies.

Bronchopulmonary dysplasia and chronic obstructive pulmonary disease are marked by neutrophilic inflammation and microbial changes. Here, the authors show the efficacy of an inhaled live biotherapeutic in reducing inflammation and improving tissue structure across models of respiratory disease.

Extrachromosomal circular DNAs (eccDNAs) affect gene expression and tumour progression. Here, the authors report a method, scCircle-seq, for eccDNA profiling in single cells, demonstrating the stochasticity, cell type specificity, and dynamics of eccDNAs in cell lines and primary tumour samples.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

High-fat diet (HFD) increases the risk of insulin resistance and non-alcoholic steatohepatitis (NASH). Here the authors report that the heat shock proteins HSP70 and GRP78 are increased in the jejunum of rats on HFD, and their continuous infusion leads insulin resistance and NASH, while in rats on a high-fat diet infused with monoclonal antibodies against HSP70 and GRP78 these phenotypes are reversed.

Here, the authors show that short-term consumption of energy-dense diets deficient in fiber, similar to eating patterns for many people today, results in a transient depression of the mucosal and systemic immune systems such that susceptibility to bacterial infection is increased.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

The cryo-EM structures of ESCRT-III CHMP2A and CHMP3 filaments reveal their mode of polymerization and interaction with negatively curved membrane. VPS4 constricts and cleaves the ESCRT-III CHMP2A–CHMP3 membrane tubes, thus acting as a minimal membrane fission machinery.

Phytoplankton blooms provoke bacterioplankton blooms, from which bacterial biomass (necromass) is released via zooplankton grazing and viral lysis. Here, Beidler et al. show that the bacterial biomass, including alpha-glucan polysaccharides generated from the consumption of algal organic matter, is reused by microbes in vitro and during a diatom-dominated bloom.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

Human primary and metastatic tumors harbor CD4⁺ T_reg cells that can suppress antitumor immune responses. Bonnal et al. identify an intratumoral type 1 T_reg-like CD4⁺ T cell subset that expresses the transcription factor EOMES, granzyme K and CHI3L2. This EOMES⁺ T cell subset correlates with disease progression but is responsive to PD-1 checkpoint blockade immunotherapy.

The authors present a public collection of 117 bacterial isolates from the pig gut, including the description of 38 novel taxa. Interesting functions discovered in these organisms include a new fucosyltransferease and sactipeptide-like molecules encoded by biosynthetic gene clusters.

The authors determined high-resolution cryo-EM structures of the lentiviral intasome — the nucleoprotein complex that inserts viral DNA into a host chromosome — and show that the architecture comprising 16 integrase subunits is critical for its function.

How intracellular cAMP activate PKA is well-characterized, but PKA inactivation remains poorly understood. Here, Rinaldi et al. show that CHIP/HSP70 ubiquitinates the catalytic subunit of PKA, with implications for the human disease spinocerebellar ataxia 16, as patients often have CHIP mutations.

The use of time-bin entangled qudits is hindered by the phase instability, timing inaccuracy and low scalability of current interferometric schemes. Here, the authors show a fiber-pigtailed photonic chip for generating and processing picosecond-spaced time-bin entangled qudits and utilize the system to implement a quantum key distribution protocol.

Mutations in proteins that localize to primary cilia cause devastating diseases, yet the primary cilium is a poorly understood organelle. Here the authors use interaction proteomics to identify a network of human ciliary proteins that provides new insights into several biological processes and diseases.

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.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

During cellular senescence in human and mouse cells, L1 transposons become transcriptionally derepressed and trigger a type-1 interferon response, which contributes to age-associated inflammation and age-related phenotypes.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Bhattacharjee and Schaeffer et al. map exclusive breastfeeding (EBF) in 94 low- and middle-income countries (LMICs), finding increased EBF practice and reduced subnational variation across the majority of LMICs from 2000 to 2018. However, only six LMICs will meet WHO’s target of ≥70% EBF by 2030 nationally, and only three will achieve this in all districts.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

Activation of brown adipose tissue (BAT) reduces the development of atherosclerosis in animal models. Here the authors show that BAT activation also increases reverse cholesterol transport and turnover of high-density lipoprotein, which likely contributes to the anti-atherosclerotic effect of BAT activation.

Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Vascular endothelial cell (EC) dysfunction contributes to the occurrence of diabetic complications. Here the authors report that in diabetic conditions, upregulation of the RNA binding protein QKI-7 in ECs due to the imbalance of RNA splicing factors CUG-BP and hnRNPM contributes to EC dysfunction, and that in vivo QKI-7 silencing improves blood flow recovery in diabetic mice with limb ischemia.

How Roquin controls expression of the inducible costimulator ICOS remains unclear. Heissmeyer and co-workers now show that Roquin binds to the 3' untranslated region of ICOS mRNA and interacts with proteins that confer post-transcriptional repression.

The connection between DNA replication timing and changes that occur to the epigenome in cancer are still poorly understood. Here, the authors perform Repli-Seq and integrated epigenome analyses and find that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Tissue fibrosis is a major contributor to mortality in the developed world. Here, the authors identify a genetic variant in the intronic region of interferon-λ4 that is a strong predictor of hepatic inflammation and fibrosis, independent of liver disease aetiology

Lyl-1 is a transcription factor expressed in hematopoietic progenitors. Goodell and colleagues show that Lyl-1 is required for lymphoid specification and the maintenance of early T lineage progenitors.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Power exhaust is one of the biggest challenges stopping fusion energy. This article shows experimental evidence for strategically shaping the power exhaust region as a solution to this challenge, utilising physics understanding to strike a balance between engineering complexity and power exhaust benefits, consistent with reduced models and simulations.

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.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

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.