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The involvement of cell death pathways in the early stage of pancreatic ductal adenocarcinoma (PDAC) development, especially KRAS-dependent acinar-to-ductal metaplasia (ADM), remains to be investigated. Here, the authors find that TAK1 mediates cell survival during ADM transdifferentiation through suppression of apoptosis and necroptosis, which could be targeted for prevention and treatment of PDAC.

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

The authors generate ~1-km² growth curves for aboveground live carbon in regrowing forests, globally. They show that maximum carbon removal rates can vary by 200-fold spatially and with age, with the greatest rates estimated at about 30 ± 12 years, highlighting the role of secondary forests in carbon cycling.

In response to the emergence of H5N1 influenza A viruses as a novel pathogen of cattle, this study shows that pasteurisation of cows’ milk should effectively inactivate the virus, but that it remains infectious in unpasteurised milk.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

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.

Nanobodies are normally made from immunized camelids, Ig transgenic mice or synthetic libraries. In this study, the authors introduce the llama Ig heavy chain locus into mice lacking this locus, thereby generating a line in which nanobodies can be made by direct immunization in the absence of an endogenous antibody repertoire.

Combining a large-scale dataset of 23 ungulate species (in which newborns follow contrasting tactics of predator avoidance) with continuous-time stochastic movement models, the authors reveal that there are multiple dimensions of maternal movement behaviour and space use.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

This study reveals that the varying responses of plant biomass to phosphorus addition across plant functional groups align with the leaf economics spectrum, with plants characterized by more acquisitive traits exhibiting stronger responses to phosphorus addition.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Carbynes are bulk linear chains of carbon atoms that can be stabilized inside carbon nanotubes. Here the authors show that while electronic states of tube and chain are decoupled, their vibrational structure is strongly altered by anharmonic interactions.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

Here, using human liver chimeric mice, the authors describe perturbation of the diurnal transcriptome and epigenome of human hepatocytes during hepatitis C virus infection, affecting pathways mediating metabolic alterations, fibrosis, and cancer, and further show that the pathways remain affected in patients with advanced liver disease.

This study shows that Crimean-Congo hemorrhagic fever virus (CCHFV) recruits apoE, an exchangeable apolipoprotein that mediates LDL/LDL-R interaction, to promote virion entry via the LDLR. Molecules that down-regulate LDL-R inhibit CCHFV infection.

Analysis of a multicenter cohort of kidney transplants shows that mismatches in the MICA locus and the presence of anti-MICA donor-specific antibodies are associated with reduced graft survival and increased rejection.

A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

Closely related plant species can have drastically different abundances of transposable elements. Now it is shown that the genome of Arabis alpina has experienced a striking expansion of retrotransposons, probably shaped by reduced DNA methylation.

Precise control of charge and spin states in quantum dots is often challenging. Here, the authors show systematic manipulation of the electron occupation in graphene nanoribbons laying on MgO.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

A label-free and low-cost sensor capable of detecting several biomarkers in parallel is a sought-after medical tool. Here, the authors describe an approach exploiting both photonic and electrochemical properties of silicon to build a multi-domain biosensor for label-free and multiplexed detection.

Examination of archaeological pottery residues and modern genes suggest that environmental conditions, subsistence economics and pathogen exposure may explain selection for lactase persistence better than prehistoric consumption of milk.

Joint initiatives by state and non-state actors launched at climate summits are expected to enhance climate governance. However, those launched at earlier summits often perform better, as do initiatives in areas such as transport, energy and industry and ones with robust institutional arrangements.

The influence of Li occupancy on electro-chemomechanical stability in Co-free Ni-rich layered oxides for Li-ion batteries has been overlooked. Here, authors investigate different Li structural units in the oxide lattice and show that tuning the Li occupancy improves battery cycling stability.

Roederer et al. estimate uptake of COVID-19 vaccines amongst migrants, homeless and precariously housed people in two regions of France with cross-sectional survey data. They also report sociodemographic factors and reasons associated with (non-)vaccination.

It has been proposed that phylogenetic diversity can be used as a proxy to estimate functional diversity and to predict ecosystem functioning. Here, the rapid evolutionary response of marine bacteria is used to study the positive effects of evolutionary history and species diversity on ecosystem productivity.

Three-dimensional genome organization is important for transcription regulation. Here the authors show that microRNA 9 mediates the formation of G-quadruplexes and the looping of promoters and super-enhancers in genes activated by transforming growth factor beta 1signaling.

Wood density is a key control on tree biomass, and understanding its spatial variation improves estimates of forest carbon stock. Sullivan et al. measure >900 forest plots to quantify wood density and produce high resolution maps of its variation across South American tropical forests.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

Twigstats, a method for ancestry reconstruction, provides high-resolution genetic histories and movement patterns of people living in Europe during the first millennium ce.

Mellman and colleagues present a multiomic single-cell analysis of the effects of combined anti-TIGIT and anti-PD-1 blockade on T cell populations trafficking from the draining lymph node to the blood and tumor.

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.

Healthy humans mount a protective immune response against Aspergillus fumigatus, an airborne opportunistic fungal pathogen, via interplay between their humoral pattern recognition molecules. Here, Dellière et al., probe the interaction between A. fumigatus and pentraxin 3 and show it restricts pro-inflammatory responses.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

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.

A significant proportion of individuals with inherited neuromuscular disease do not receive a genetic diagnosis. Here, the authors establish CCG expansions in the 5’ untranslated region of ABCD3 as a cause of oculopharyngodistal myopathy (OPDM) in individuals of European ancestry and identify increased expression of expansion-containing ABCD3 transcripts as a possible disease mechanism underlying muscle degeneration.

Strong intrinsic spin–orbit interaction unlocks the potential of circuit quantum electrodynamics with hole spins in silicon, resulting in strong spin–photon coupling of 300 MHz.

Native oyster reef ecosystems were decimated by human activities, with little known of their past extent. This study evaluates historical records to show that oyster reefs were once a dominant feature of European coastlines and provides perspectives for current management strategies.