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Non-variceal upper gastrointestinal bleeding is a medical emergency in which bleeding develops in the oesophagus, stomach or proximal duodenum and is often caused by peptic ulcers as a result of Helicobacter pylori infection, NSAID use or low-dose aspirin use. This Primer describes how these bleeding events occur and how to resolve this common clinical problem.

Nonvariceal upper gastrointestinal bleeding (UGIB) is a major cause of morbidity and mortality worldwide, and despite improvements in the management of patients with this condition, there have only been moderate improvements in mortality rates. This Review discusses the diagnosis of UGIB and describes the optimal management of patients with this condition, in accordance with the current consensus recommendations and contemporary literature. The authors examine endoscopy, management of bleeding and pharmacological therapy for patients with UGIB.

This study maps the connections of layer 5 pyramidal neurons in the mouse cortex, revealing distinct local and intercortical wiring patterns, and provides an open framework for exploring the connectivity of cell types.

The authors use Patch-seq and electron microscopy datasets to relate synaptic connectivity to the transcriptomic cell type of different types of inhibitory neuron.

Neural Decomposition (NEURD) is a software package that decomposes neuronal data from high-resolution electron microscopy volumes into feature-rich graph representations to facilitate analysis for neuroscience research.

Hagenbeek et al. identify a small-molecule pan-TEAD inhibitor that blocks the interaction between YAP/TAZ and TEAD proteins. They demonstrate that treatment with the inhibitor leads to antitumor activity and can synergize with KRAS G12C inhibition.

The MICrONS mouse visual cortex dataset shows that neurons with similar response properties preferentially connect, a pattern that emerges within and across brain areas and layers, and independently emerges in artificial neural networks where these ‘like-to-like’ connections prove important for task performance.

Excitatory neurons in the neocortex exhibit considerable morphological diversity, yet their organizational principles remain a subject of ongoing research. Here, the authors use unsupervised learning to show that most excitatory neuron morphologies in the mouse visual cortex form a continuum, with notable exceptions in deeper layers.

The Connectome Annotation Versioning Engine (CAVE) is a platform for proofreading, annotating and analyzing datasets reaching the petascale. Currently, CAVE is used for electron microscopy datasets, but it can potentially be used for other large-scale datasets.

Using volumetric electron microscopy, the authors map and analyze the structure of cortical inhibition with synaptic resolution across a column of visual cortex.

An analysis demonstrates that quantitative measurements of perisomatic ultrastructure features of neurons can be used to categorize them into cell types.

The 16p11.2 duplication confers risk for autism and schizophrenia, but the disease mechanisms are unknown. Here, the authors use proteomics to show dysregulation of synaptic and epilepsy-associated protein networks in the cortex of model mice, and demonstrate that correcting Prrt2 gene dosage rescues circuit hypersynchrony and behavioural phenotypes.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Functional miRNA targets are identified transcriptome-wide in single cells.

A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

The many strongly interacting degrees of freedom in transition metal oxides make it difficult to capture and describe the nature of their metal-insulator transitions. Li et al. show that a resonant magnetic X-ray nanoprobe gives access to local critical behavior that is difficult to detect otherwise.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

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.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

The first annotated chromosome-level reference genome assembly for pea, Gregor Mendel’s original genetic model, provides insights into legume genome evolution and the molecular basis of agricultural traits for pea improvement.

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.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

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.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Fungi originated in a freshwater environment and their evolution accompanied the rise of algae and land plants. In this Review, Berbee and colleagues examine the fossil and genomic record of ancient fungi and the inferences we can make about their lifestyle.

The authors pooled resources to identify best practices and develop a new standardized protocol for estimating functional connectivity in rats with magnetic resonance imaging.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

The morphology of dendrites and dendritic spines changes with development and as a result of activity-dependent plasticity mechanisms. Penzes and colleagues describe the altered dendritic structural plasticity that is associated with some neuropsychiatric disorders and consider the underlying molecular mechanisms, based on recent genetic discoveries.

An in vivo transposon screen in a pancreatic cancer model identifies frequent inactivation of Usp9x; deletion of Usp9x cooperates with Kras^G12D to accelerate rapidly pancreatic tumorigenesis in mice, validating their genetic interaction.