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Pancreatic cancer is not caused by a specific series of genetic alterations that occur sequentially but by one, or few, catastrophic events that result in simultaneous oncogenic genetic rearrangements, giving rise to highly aggressive tumours.

Missegregated chromosomes that are sequestrated in micronuclei are subject to changes in histone modifications leading to abnormalities in chromatin accessibility that remain long after the chromosomes have been reincorporated into the primary nucleus.

Whether invasive species must first establish in conditions within their native climatic niche before spreading remains largely untested. This study presents the Niche Margin Index for estimating climatic niche-matching of alien mammal species to a particular site, which could be used to help predict the success of invasions.

The pilot phase of PigGTEx, re-analyzing 5,457 published RNA-seq samples, presents a pan-tissue catalog of molecular quantitative trait loci. Cross-species comparisons identify traits with shared genetic regulation in humans.

Computational, experimental and structural analyses reveal an abundant, nucleoid-associated histone and an alternative mode for DNA binding in vitro in the bacterium Bdellovibrio bacteriovorus.

Enzymatic catalytic processes have great industrial potential, although their application is hampered by stability and reuse issues. Here, the authors report metal-organic frameworks with rationally designed single-molecule traps for enzyme encapsulation, and evaluate the activity of the confined enzymes.

SARS-CoV-2 variants with mutations in spike have emerged during the pandemic. Magaret et al. show that in Latin America, efficacy of the Ad26.COV2.S vaccine against moderate to severe–critical COVID-19 varied by sequence features, antibody escape scores, and neutralization impacting features of the SARS-CoV-2 variant.

An analysis of fish and macroinvertebrate communities in European rivers over 32 years shows that inland ship traffic is associated with declining taxonomic richness, diversity and trait richness and with increased taxonomic evenness.

The giant planet 8 Ursae Minoris b seems to have avoided engulfment by its giant host star through a stellar merger that either affected the evolution of the host star or produced 8 Ursae Minoris b as a second-generation planet.

Meningococcus utilizes β-arrestin selective activation of endothelial cell β2 adrenergic receptor (β2AR) to cause meningitis in humans. Here authors report that Meningococcus triggers β2AR signaling by exerting forces on β2AR glycans that terminally expose N-acetyl-neuraminic acid (sialic acid, Neu5Ac) residues.

MADS transcription factors regulate multiple aspects of plant development. Here the authors show that the intervening I domain is conserved in both type I and type II plant MADS lineages and contributes to the functional identity of the protein by influencing both DNA binding activity and dimerisation specificity.

A mouse mutagenesis screen identifies CYRI (FAM49B) as a host protection factor against Salmonella infection. CYRI negatively regulates RAC1 signalling to interfere with bacterial entry and dissemination.

By comparing the metabolomes, transcriptomes and epigenomes of human pluripotent stem cell lines, Sperber et al. show that interplay between the metabolome and histone modifications drives the metabolic switch from naive to primed pluripotency.

Directed cell movement known as durotaxis, typically associated with cellular migration in response to a substrate gradient of increasing stiffness, is now shown to also occur in the opposite direction, following a gradient of decreasing stiffness.

RIPK1 kinase activity is known to transduce a death signal, but the molecular mechanisms that normally prevent RIPK1 activation are unclear. Here, the authors report that IKK-mediated phosphorylation on RIPK1 Ser25 directly represses its enzymatic activity and thus RIPK1-dependent cell death.

Cilia are composed of cytoskeletal filaments and molecular motors and are characterized by a wave-like motion. Here the authors show that this motion is reconstituted in vitro from the self-assembly of polymerizing actin filaments and myosin motors.

Despite functional optimisation during evolution of parasitism, most members of a calcium dependent protein kinase (CDPK) family show genetic redundancy in Plasmodium. Here, the authors screen 294 genetic interactions among protein kinases in Plasmodium and show how some CDPKs functionally interact to control motility and host cell invasion.

Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth.

Hybridization can contribute to diversity from the genomic to the species level. Here, Eberlein, Hénault et al. investigate genomic, transcriptomic and phenotypic variation among wild lineages of the yeast Saccharomyces paradoxus and suggest that an incipient species has formed by recurrent hybridization.

In electromechanical devices, nonlinear radiation-pressure interaction can lead to significant changes in the dynamics from just few photons. Here, by enhancing the light-matter coupling in a cavity electromechanical device, the author show the onset of mechanical instabilities with less than a single photon in the cavity.

Genetic variants in RP1 can cause hereditary retinal degeneration (HRD). Here, in a genomic screen of 331 Japanese HRD patients, the authors identify a near-polymorphic RP1 variant that causes Mendelian HRD in trans with an Alu insertion and otherwise is associated with HRD according to a complex model of inheritance.

Detailed atomic models of axonemes from algal flagella and human respiratory cilia, which are hair-like protrusions from cells that enable motility and clear mucus from human airways, could provide insights into how they function.

The Aurora kinases orchestrate chromosome segregation and cell division. Zeeshan et al. studied divergent Plasmodium ARK2 and EB1 using live cell imaging, proteomics and functional genetics. These are critical components for atypical spindle dynamics during transmission stages.

This directory was made possible by a unique international collaboration between the 633 scientists whose names appear below. It represents both the first published description of the complete sequence of most chromsomes from Saccharomyces cerevisiae, and the first published overview of the entire sequence. As such, the authors would like future papers referring to the entire sequence and/or its contents to cite this directory; future papers referring to the sequence of individual chromosomes should refer to the papers listed at the head of page 9. The authors’ affiliations appear in the papers describing the individual chromosomes.

Pain experience is highly individual, but its individual-specific brain features remain unclear. The authors identify brain regions with consistent versus variable representations of pain across a large sample of individuals.

Pugh and colleagues use single-cell RNA sequencing, CRISPR screens and functional assays to define a gradient of developmental and wound-response cell states in glioblastoma stem cells, revealing insights into glioblastoma origins and potential therapeutic targets.

Receptor interacting protein kinase 1 (RIPK1) regulates cell death and inflammatory responses. Here the authors show that autophosphorylation at Ser166 is required for RIPK1-mediated cell death and inflammation in mouse models of inflammatory pathologies, making Ser166 phosphorylation a possible biomarker for RIPK1-mediated inflammatory diseases.

Expanding pore sizes and volumes in metal-organic frameworks is challenging, but crucial for the encapsulation of larger guest molecules. Here, Zhou and colleagues report a linker labilization strategy to construct MOFs containing hierarchical pore architectures with dimensions ranging from 1.5 to 18 nm.

Genomes of three Tuberaceae species and two related truffle species reveal genetic similarities across symbiotic truffle-forming fungi, including high expression of genes involved in volatile organic compound metabolism.

Creatine can be used for thermogenesis in adipocytes. Here Kazak et al. show that creatine uptake is required to sustain this thermogenic pathway. Knockdown of the creatine transporter, CrT, in adipocytes decreases thermogenesis and energy expenditure, whereas creatine supplementation increases energy expenditure in mice fed a high-fat diet.

The long non-coding RNA locus Maenli controls mouse limb development by regulating En1 activity, and the absence of the homolgous MAENLI locus is associated with severe congenital limb defects in humans.

Metal-organic framework glasses are gaining interest, but large samples are difficult to fabricate and mechanical properties are not well understood. Here, the authors use experiments and simulations to assess fracture toughness and flexural strength of a zeolitic imidazolate framework glass.

The regulation of gene expression underlies many forms of learning and behaviour in the mammalian brain. Carpenter et al. define a molecular mechanism whereby Nr4a1 activation leads to persistent changes in gene expression, chromatin and behaviour, in the context of cocaine abstinence.

FOXA1 pioneer transcription factor is recurrently mutated in primary and metastatic prostate tumors. Here, authors identify a set of six cis-regulatory elements in the FOXA1 regulatory plexus harboring somatic SNVs in primary prostate tumors and characterize their role in regulating FOXA1 expression and prostate cancer cell growth.

Alkaline ceramidases (ACERs) are a class of poorly understood transmembrane enzymes controlling the homeostasis of ceramides. Here authors solve the Xray structure of human ACER3 and uncover a Ca2+ binding site providing an explanation for the known regulatory role of Ca2+ on ACER3 activity.

Numerous strategies exist to limit the off-target activity of CRISPR-Cas9 nucleases. Here the authors co-administer truncated gRNAs that block both Cas9 and high-fidelity Cas9 variants from cleaving at off-target sites.

Ocean sediment records suggest that the modern Antarctic Circumpolar Current did not exist before the late Miocene cooling, indicating its origin is linked to the expansion of the Antarctic Ice Sheet.

White-tailed deer are a potential reservoir of SARS-CoV-2 variants.

Phospholamban (PLN) is a regulator of heart contractility. Here the authors show that cardiomyocytes derived from induced pluripotent stem cells of a cardiomyopathy patient with mutant PLN exhibit functional defects consistent with the disease, and that this mutation can be functionally corrected by genome editing and gene therapy.

Nature uses out-of-equilibrium systems to control hierarchical assembly. Now, a dissipative chemical system has been shown to slowly release monomer DNA strands from a high-energy reservoir, regulating self-assembly by switching the mechanism of supramolecular polymerization at the single-molecule level. This process heals fibre defects, converting branched, heterogeneous networks into nanocable superstructures.

Here the authors report that DNA:RNA hybrid-containing R-loop structures are sensed by the ssDNA-binding protein RPA, triggering their relocation to nuclear pore complexes and attenuating transcription-associated genetic instability.

Multiple alternative splicing events in CD19 mRNA have been associated with resistance/relapse to CD19 CAR-T therapy in patients with B cell malignancies. Here, by combining patient data and a high-throughput mutagenesis screen, the authors identify single point mutations and RNA-binding proteins that can control CD19 splicing and be associated with CD19 CAR-T therapy resistance.

ABACUS2 Förster resonance energy transfer biosensors allow an unparalleled view of abscisic acid accumulations and depletions in living plants. Well-watered roots accumulate abscisic acid in growing cells upon shoot dehydration and this is essential to maintain root growth under low humidity.