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Drug resistance remains a major challenge in cancer treatment. Here, the authors identify Connexin43 as target that enhances BRAF/MEKi efficacy by interfering with DNA repair pathways, overcoming drug resistance. They develop an mRNA therapy that improves efficacy and sensitizes resistant cells.

High-dimensional datasets derived from time-resolved live imaging of leukocytes in mice were used to identify leukocyte identities and dynamic neutrophil states with high cellular resolution.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

TOI-500 hosts at least four planets, the innermost of which is an Earth-sized ultra-short-period body with a density similar to Earth. The architecture of the TOI-500 system can be explained by a slow, secular, low-eccentricity migration scenario.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

Tropical forest leaves are expected to absorb more of the Sun’s energy with climate warming, which could further increase global temperatures.

Hyperbolic phonon polaritons occurring in anisotropic materials exhibit strong light confinement and propagation directionality. Matson et al. report real-space imaging and control of recently discovered hyperbolic shear phonon-polaritons in beta-Ga2O3, arising from symmetry breaking in the dielectric response.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

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.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

Guillaume Lettre, Alexander Reiner, George Diaz and colleagues use an exome array to identify rare and low-frequency coding variants influencing hematological traits. They find several missense variants in CXCR2 associated with reduced white blood cell counts, and, in a separate family-based study, they identify a homozygous CXCR2 frameshift mutation in two siblings with congenital neutropenia.

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.

Here, the authors describe the global distribution of crAssphage, its presence in Old-World and New-World primates, and its association with gut bacterial communities and dietary factors, providing insights into the origin, evolution and epidemiology of human gut crAssphage.

The Large Hadron Collider beauty collaboration reports a test of lepton flavour universality in decays of bottom mesons into strange mesons and a charged lepton pair, finding evidence of a violation of this principle postulated in the standard model.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

A pan-cancer epigenetic and transcriptomic atlas identifies epigenetic drivers associated with cancer transitions.

How the immune response is involved in the response to multiple myeloma after treatment is not fully understood. Here the authors investigate how lenalidomide treatment in newly diagnosed MM patients affects the immune microenvironment in the blood and bone marrow and compare between responses to treatment.

Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Planar cell polarity (PCP) regulates hair cell orientation in the zebrafish lateral line. Here, the authors show that mutating Wnt pathway genes (wnt11f1, fzd7a/b, and gpc4) causes concentric hair cell patterns not regulated by PCP, thus showing PCP/Wnt pathway genes have different consequences on hair cell orientation.

Ji et al. identify an idiopathic generalised epilepsy network that links heterogeneously distributed brain abnormalities to a common brain network and deep brain stimulation sites which reduce generalised seizures.

Markov, Ren, Senkow and colleagues report that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterized patients who recovered, whereas responses against nonstructural proteins and activation of NF-κB were associated with poor outcomes.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Many island plant species share a syndrome of characteristic phenotype and life history. Cerca et al. find the genomic basis of the plant island syndrome in one of Darwin’s giant daisies, while separating ancestral genomes in a chromosome-resolved polyploid assembly.

Human brain structure changes throughout the lifespan. Brouwer et al. identified genetic variants that affect rates of brain growth and atrophy. The genes are linked to early brain development and neurodegeneration and suggest involvement of metabolic processes.

The LHCb collaboration reports an improved measurement of the oscillation frequency of mesons consisting of a bottom quark and strange quark, which is then combined with previous results.

The directional propagation of phonon polaritons has been demonstrated in various twisted van der Waals materials. Here, the authors report a complementary type of directional polariton propagation by visualizing unidirectional ray polaritons in twisted asymmetric stacks of α-MoO3 and/or β-Ga2O3.

Analyses of five treponemal genomes representing ancient relatives of Treponema pallidum suggest that this pathogen originated in the Americas.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

SAMHD1 catalyses the dephosphorylation of deoxynucleotide triphosphates (dNTPs) and has antiretroviral activity. Here, the authors present the crystal structures of SAMHD1-oligonucleotide complexes, which reveal that the allosteric binding sites of SAMHD1 are plastic and can fit oligonucleotides in place of the two allosteric activators GTP and dNTP, and they also show that SAMHD1 recognises GpsN phosphorothioation modifications in nucleic acids, which is of interest in drug design.

Alternative stable states in forests have implications for the biosphere. Here, the authors combine forest biodiversity observations and simulations revealing that leaf types across temperate regions of the NH follow a bimodal distribution suggesting signatures of alternative forest states.

Leukemias with ambiguous lineage require further characterisation. Here, the authors perform epigenomic and transcriptomic analysis of a subgroup of such leukemias with CpG Island Methylator Phenotype and propose that epigenetic dysregulation and not genetic lesions explains their mixed phenotype.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

The existence and properties of tetraquark states with two heavy quarks and two light antiquarks have been widely debated. Here, the authors use a unitarized model to study the properties of an exotic narrow state compatible with a doubly charmed tetraquark.

A genomic, transcriptomic and epigenomic analysis of chronic lymphocytic leukemia identifies genetic drivers and molecular subtypes associated with clinical outcomes.

Ultra-sensitive cell-free DNA (cfDNA) sequencing uncovers clonal hematopoiesis as a major source of somatic cfDNA variants in healthy individuals and patients with cancer, and underscores the importance of matched white blood cell DNA sequencing in liquid biopsy procedures.

CP violation has deep implications for particle physics and cosmology. Previously observed only in meson decays, signs of CP violation have now been spotted in baryon decays by analysing the proton–proton collision data from the LHCb detector.

Programmable, RNA-guided nucleases are diverse enzymes that have been repurposed for biotechnological applications. Here, the authors mine an extensive genome-resolved metagenomics database and identified uncharacterized families of RNA-guided, compact nucleases.

The authors show in a preclinical large animal model that in utero delivery of FVIII-secreting human placental cells is feasible, safe, and yields elevated plasma FVIII activity for at least three years without triggering immunity, affirming prenatal treatment of hemophilia A.

Interactions of atmospheric neutrinos with quantum-gravity-induced fluctuations of the metric of spacetime would lead to decoherence. The IceCube Collaboration constrains such interactions with atmospheric neutrinos.

There is currently no disease-modifying treatment for Parkinson’s disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome.

By demonstrating a computational approach to restore the clinical efficacy of a COVID-19 antibody, the potential to rapidly update clinical antibodies is explored.

Performing multiple histological stains on a biopsy can be costly and time consuming. Here the authors present a method for the digital transformation of H&E stained tissue into special stains (e.g., PAS, Masson’s Trichrome and Jones silver stain), and demonstrate that it improves diagnoses over the use of H&E only.

Untreated, postconsumer-PET from 51 different thermoformed products can all be almost completely degraded by FAST-PETase in 1 week and PET can be resynthesized from the recovered monomers, demonstrating recycling at the industrial scale.

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.

Taxonomical complexity has muddled the classification of clinically relevant Enterobacter species. Authors carry out a genome-based study on clinical isolates to investigate colistin resistance and heteroresistance in Enterobacter.