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Connectomics, the comprehensive mapping of neural circuits at nanoscale resolution, has historically relied on electron microscopy (EM), both transmission (TEM) and scanning (SEM). However, as connectomics scales towards larger brain volumes and whole mammalian brains, substantial technical challenges emerge. Here, we highlight key challenges and advancing approaches that hold promise, particularly those that integrate three-dimensional, multi-resolution and time-resolved imaging to capture both long-range and local wiring, down to supramolecular resolution.

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

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

In this case series of patients with T cell acute lymphoblastic leukemia (T-ALL), therapy with CD7-directed CAR T cells that express an anti-CD7 protein expression blocker to prevent CAR T-induced fratricide showed encouraging rates of clinical response and persistence of circulating CAR T cells.

We use connectomics to compare the wiring logic of premotor circuits controlling the Drosophila leg and wing, finding that both premotor networks cluster into modules that link motor neurons innervating muscles with related functions.

Sequencing analysis of tamoxifen-associated uterine cancers and further in vivo analyses suggest that the drug tamoxifen can activate the PI3K pathway in the absence of oncogenic mutations.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

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.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

A multi-modal analysis of pre-metastatic liver biopsies from patients with localized pancreatic cancer with a minimum of 3 years of follow-up shows that immunological, proliferative and metabolomic features distinguish patients who develop metastases from disease-free survivors and can be used to predict outcomes.

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.

Comprehensive profiling of a circumventricular organ with leaky blood vessels, and comparison to cortex vasculature reveal that blood–brain barrier heterogeneity reflects differences in endothelial cells and their interactions with perivascular cells.

A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

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 sarcoplasmic (SR) and endoplasmic reticulum (ER) are involved in heart development but how this arises is unclear. Here, the authors show that loss of a SR/ER protein REEP5 causes membrane destabilization and decreased cardiac myocyte contractility, with cardiac dysfunction in mutant mouse and zebrafish models.

Seismic imaging of subducted plates offers a way to improve plate tectonic reconstructions. Here, Braszus et al. use new ocean-bottom seismometer data from the Lesser Antilles to locate subducted spreading centres and faults thus providing a new understanding of the evolution of the Caribbean plate.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

Infusion of virus-specific T (VST) cells is used for treating drug-resistant viremia. Here the authors report, as part of the clinical trial, NCT03475212, a lethal case of unexpected bone marrow graft loss and chimerism reversal that is induced by the infusion of third-party VST intended to treat transplantation-related cytomegalovirus viremia.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Relating T cell receptor (TCR) sequencing to antigen specificity is a challenge especially when TCR specificity is unclear. Here the authors use a low dimensional generative approach to model TCR sequence similarity and to associate TCR sequences with the same specificity.

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.

Hong Kong experienced a severe wave of SARS-CoV-2 in early 2022. Here, the authors use genomic and serosurveillance data and show that this wave was dominated by the Omicron BA.2 sublineage, and that low protective immunity, particularly in older age groups, contributed to its severity.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Long-term tracking of learned actions in mouse motor cortex shows that learned actions are retained with their context, and learning new tasks creates new memories, which do not overwrite or modify existing representations.

By implementing random circuit sampling, experimental and theoretical results establish the existence of transitions to a stable, computationally complex phase that is reachable with current quantum processors.

Three electron microscopy datasets are combined to provide a complete connectomic description of the neural circuitry that makes up the neck connective in Drosophila, including the descending neurons, ascending neurons and sensory ascending neurons.

A study reports single-cell RNA-sequencing profiles for more than 1.6 million cell nuclei from 101 whole mouse embryos including 22 mutant and 4 wild-type genotypes, from one experiment.

SynapShot combines ddFPs with engineered synaptic adhesion molecules for real-time observation of the structural plasticity of synapses in cultured cells and animals.

Excitatory pyramidal neurons preferentially target inhibitory interneurons with the same selectivity and, in turn, inhibitory interneurons preferentially target pyramidal neurons with opposite selectivity, forming an opponent inhibition motif that supports decision-making.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

The antibody response to COVID-19 vaccines varies among individuals. Here the authors find that older age, male sex, smoking, higher BMI, vaccine type, and certain comorbidities are associated with lower anti-S1 antibody levels after COVID-19 vaccinations, indicating that certain groups might benefit from higher frequency or doses of vaccination.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

A study reports the development and validation of a wrist-worn, consumer wearable-based system that identifies sudden loss of pulse events with a performance profile suitable for societal-scale use.

Coastal upwelling regions are among the most productive marine ecosystems but may be threatened by amplified ocean acidification. Here the authors show from community to molecular levels that phytoplankton in an upwelling region respond to short-term acidification exposure with iron uptake pathways and strategies that reduce cellular iron demand.

RAG2-SCID is a primary immunodeficiency caused by mutations in Recombination-activating gene 2 (RAG2). Here the authors report a RAG2 correction strategy that replaces the entire endogenous coding sequence (CDS) to maintain the endogenous spatiotemporal gene regulation and locus architecture.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

Here authors show that machine learning derives the degree of background retinal pigmentation with more nuance than self-described ethnicity. Retinal pigment scores are associated with genes linked to melanin and may improve algorithmic fairness.