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Engineered aminoacyl-tRNA synthetase (aaRS) mutants have been developed that facilitate ultrafast bioorthogonal noncanonical amino acid tagging (BONCAT) of newly synthesized proteins in diverse bacteria, including ESKAPE pathogens. The substrate polyspecificity of the aaRS mutants enables pulse-chase BONCAT and differential tagging of temporally distinct nascent proteomes in cells.

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.

Doerig, Kietzmann and colleagues show that the brain’s response to visual scenes can be modelled using language-based AI representations. By linking brain activity to caption-based embeddings from large language models, the study reveals a way to quantify complex visual understanding.

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.

By analysing the smartphone data of 2,112,288 participants, in particular observing and comparing the activity of the same individual in two different environments, we find that increases in the walkability of environments result in increases in daily physical activity, providing evidence of the importance of the built environment on physical health.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

A large language model designed for health monitoring provides personalized sleep and fitness predictions, insights and advice.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

The expression of each of the roughly 22,000 genes of the mouse genome has been mapped, at cellular resolution, across all major structures of the mouse brain, revealing that 80% of all genes appear to be expressed in the brain.

Accounting for water hosted in serpentinsed peridotites (not preferentially located near fracture zones) increases by 50% the budget of water subducted by Atlantic crust, according to assessment of P- and S-wave seismic velocities.

A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders.

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.

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

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The newest chapter in James Lovelock's Gaia saga holds out hope, finds Tim Lenton.

Tim Radford reassesses the independent scientist’s groundbreaking body of writing.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

Using transcriptomic data from human brain cells, the authors show that the expression patterns of the genes implicated in human cognition and brain evolution overlap in specific neuron types, and relate to cellular function and structure.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Kidney transplantation usually relies on hypothermia to safely preserve the graft. Here, the authors show that keeping kidneys at 37°C, using a machine to supply them with blood, oxygen, and nutrition, is feasible for up to 24 hours, and may be useful for testing and treating them pre-transplant.

Pycytominer is a user-friendly, open-source Python package that carries out key bioinformatics steps in image-based profiling.

Group 2 Innate lymphoid cells (ILC2) are a source of type 2 cytokines, such as interleukin-5 (IL-5). Here Troch, Jakob et al. show a non-redundant role of ILC2-derived IL-5 required for the development and function of a subset of murine B cells.

VIP interneurons have been shown to disinhibit pyramidal neurons by inhibiting other interneuron types. Here, the authors report that ChAT-VIP subtype of interneurons directly excite pyramidal neurons in multiple layers via fast cholinergic neurotransmission.

Discovering that nociceptive sensory neurons express the receptor for anthrax toxin, Yang et al. show that anthrax toxin can induce potent analgesia in mice and facilitate the delivery of potentially analgesic cargo proteins into nociceptive neurons.

Gouwens et al. established a morpho-electrical taxonomy of cell types for the mouse visual cortex via unsupervised clustering analysis of multiple quantitative features from 1,938 neurons available online at the Allen Cell Types Database.

Gaia Vince takes an enjoyable sprint through human evolution — Tim Radford reviews.

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Gene selection for spatial transcriptomics is currently not optimal. Here the authors report PERSIST, a flexible deep learning framework that uses existing scRNA-seq data to identify gene targets for spatial transcriptomics; they show this allows you to capture more information with fewer genes.

Combined analysis of new genomic data from 116 ancient hunter-gatherer individuals together with previously published data provides insights into the genetic structure and demographic shifts of west Eurasian forager populations over a period of 30,000 years.

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.

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.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

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.

Mammalian cortex comprises a variety of cells, but the extent of this cellular diversity is unknown. The authors defined cell types in the primary visual cortex of adult mice using single-cell transcriptomics. This revealed 49 cell types, including 23 GABAergic, 19 glutamatergic and 7 non-neuronal types.

This paper discusses how experimental and computational studies integrating multimodal data, such as RNA expression, connectivity and neural activity, are advancing our understanding of the architecture, mechanisms and function of cortical circuits.

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.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Here, the authors design a multiplex serology platform to quantitatively measure antibodies against 20 infectious agents in UK Biobank participants and confirm associations of antibody responses with sociodemographic characteristics, HLA genetic variants, and disease outcomes.

Wolfram syndrome, caused by WFS1 or CISD2 gene mutations, disrupts ER Ca²⁺ regulation in neurons. Here, the authors show how these mutations impair ER-mitochondria interactions, compromise Ca²⁺ transfer and mitochondrial function, and lead to bioenergetic deficits and oxidative stress.

By comparing neural responses to diverse visual stimuli measured with a standardized two-photon imaging pipeline, the authors reveal response specializations within the mouse visual cortex.