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While autoinhibited architectures of talin are known from cryo-electron microscopy, its behaviour in solution has remained underexplored. Here, the authors use size-exclusion chromatography coupled with in-line small-angle X-ray scattering, Monte Carlo modeling and AlphaFold predictions to determine the conformational landscape of full-length talin in solution, showing that this cytoplasmic adapter protein does not adopt a single compact structure but instead populates a broad, flexible conformational ensemble characterized by R3 subdomain repositioning and partial F3-R9 subdomain disengagement.

Using viral barcode tracing to detect interactions between glioblastoma cells and non-malignant astrocytes in patient samples, investigators discovered a pathway that reduces tumour-specific immunity and identified potential therapeutic targets.

The authors observe a reduction in thermal conductivity when transitioning from single to multi-cation oxides, exploring the role of local bonding distortions in phonon scattering and thermal transport.

BPTF is known to regulate chromatin accessibility and self-renewal in mammary epithelial stem cells. Here, the authors discover that BPTF inhibition delays tumor formation, re-activates ERα expression, increases sensitivity to tamoxifen treatment, and inhibits metastatic development.

Understanding mechanisms for obtaining low thermal conductivity without degraded electrical properties remains a challenge. Here, the authors reveal a mechanism for thermal conductivity reduction in a Zintl phase thermoelectric based on length scales for disorder in Eu₂ZnSb₂.

WNT/β-catenin signaling is an essential regulator of many developmental processes. Here, the authors provide evidence that activation of the WNT in human pluripotent stem cells leads to expression WNT target gene SP5, which then acts to diminish expression of active WNT target genes.

Materials with tunable thermal properties enable on-demand control of temperature and heat flow. Here, the authors demonstrate how thermal conductivity of an antiferroelectric solid can be bi-directionally switched to 10% lower and 25% higher values without any moving components.

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.

Sun and Jin et al. report that a population of neurons in the subiculum form a pathway for visual information to reach the hippocampus and impact place-specific activity. Activation of these neurons promotes the formation of object-location memories.

Sex pheromones that increase mating have been reported across a number of different species, yet there is little known about pheromones that suppress female mating drive. This study reports that juvenile female mice release a pheromone, ESP22, which suppresses sexual receptivity of adult female mice by evoking a robust rejection behavior upon male mounting.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Ten people who mattered this year.

The multipass membrane transporter MFSD6 localizes to the plasma membrane and acts as a host entry factor for enterovirus D68 (EV-D68) by binding directly to EV-D68 particles through its extracellular, third loop, offering a potential target to combat infections by this emerging pathogen.

Urinary tract infections (UTIs) can elicit systemic host-responses. Here the authors report that, in a mouse model, unresolved UTI is associated with alterations of the mammary tissue, including collagen deposition and hyperplasia.

Viruses are transduced to single cells in tissues, organoids and in the mouse brain using mechanical carriers.

Of 12 serology assays tested, four detect antibodies in more than 80% of patients with COVID-19.

The central amygdala relies on inhibitory circuitry to encode fear memories, but how this information is acquired and expressed in these connections is unknown. Two new papers use a combination of cutting-edge technologies to reveal two distinct microcircuits within the central amygdala, one required for fear acquisition and the other critical for conditioned fear responses. Understanding this architecture provides a strong link between activity in a specific circuit and particular behavioural consequences.

Developmental disorders (DDs) are more prevalent in males, thought to be due to X-linked genetic variation. Here, the authors investigate the burden of X-linked coding variants in 11,044 DD patients, showing that this contributes to ~6% of both male and female cases and therefore does not solely explain male bias in DDs.

Structural and functional studies reveal how viral proteins trigger the phage antirestriction induced system (PARIS) to degrade host tRNA and how viral tRNAs suppress the PARIS nuclease and thereby overcome this phage defense system.

Deborah Mackay and colleagues identify mutations in ZFP57, encoding a zinc-finger transcription factor, in families with transient neonatal diabetes and additional clinical features. Affected individuals have a variable pattern of DNA hypomethylation at multiple imprinted loci.

By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.

Growing demand for food is confronting constraints to its sustainable production. This study finds that intercropping increases grain yields and their stability and that yield benefits increase over time.

Mesoscale connectomic mapping of the cortico–basal ganglia–thalamic network reveals key architectural and information processing features.

We report on the promising thermoelectric performance of p-type polycrystalline BiCuSeO, which is a layered oxyselenide composed of conductive (Cu₂Se₂)²⁻ layers that alternate with insulating (Bi₂O₂)²⁺ layers. Electrical transport properties can be optimized by substituting Bi³⁺ with Ca²⁺. Moreover, BiCuSeO shows very low thermal conductivity in the temperature ranges of 300 (∼0.9 W m⁻¹K⁻¹) to 923 K (∼0.45 W m⁻¹ K⁻¹). These intrinsically low thermal conductivity values may result from the weak chemical bonds of the material as well as the strong anharmonicity of the bonding arrangement. The combination of the optimized power factor and the intrinsically low thermal conductivity results in a high ZT of ∼0.9 at 923 K for Bi_0.925Ca_0.075CuSeO.

Somatic mutations drive the clonal proliferation of myeloproliferative neoplasms. Here the authors conduct a genome-wide association study and identify germline variation at multiple loci associated with the development and disease phenotype of these cancers.

The authors use chronic in vivo imaging to study pyramidal neurons before and after deletion of the tumor suppressor gene Pten in mature neurons of the mouse cortex. They find that Pten/mTOR signaling only regulates growth of layer 2/3 apical dendrites.

In mouse, an axonal connectivity map showing the wiring patterns across the entire brain has been created using an EGFP-expressing adeno-associated virus tracing technique, providing the first such whole-brain map for a vertebrate species.

Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.

It has been thought that blue-yellow color opponent cells in the primate retina receive little input from rods. Here, the authors report that rod and cone signals are multiplexed in blue-yellow cells and that this may be the source of the blue hue bias in night vision.

An atomic force microscope and confocal microscope set-up that allows nanomechanical mapping of virus binding under cell culture conditions shows that the first binding steps of a virus to a cell surface receptor are specific and weak, but affinity increases as more bonds are formed between the virus and cell surface receptors.

Eukaryotes acquired their prokaryotic genes in two episodes of evolutionary influx corresponding to the origin of mitochondria and plastids, respectively, followed by extensive differential gene loss, uncovering a massive imprint of endosymbiosis in the nuclear genomes of complex cells.

Computationally designed icosahedral protein-based assemblies can protect their genetic material and evolve in biochemical environments, suggesting a route to the custom design of synthetic nanomaterials for non-viral drug delivery.

A database of known drug-gene interactions, with information derived from many public sources, allows the identification of genes that are currently targeted by a drug and the membership of genes in a category, such as kinase genes, that have a high potential for drug development.

An analysis of 101 ancient human genomes from the Bronze Age (3000–1000 bc) reveals large-scale population migrations in Eurasia consistent with the spread of Indo-European languages; individuals frequently had light skin pigmentation but were not lactose tolerant.

Hexagonal boron nitride has been theoretically predicted to have high values for its thermal conductivity which would make it useful for thermal management of devices but these values have not been experimentally achieved. The authors manipulate the isotope concentration of B to increase the thermal conductivity and reach these predicted values.

The ability to target and manipulate specific neuronal populations is crucial for understanding brain function. In this report, the authors describe a novel virus that restricts gene expression to telencephalic GABAergic interneurons, allowing for morphological visualization, activity monitoring and functional manipulation of interneurons in mice and in non-genetically tractable species.

This paper demonstrates that orientation maps, as found in the cortex of higher mammals, are likely to arise from the spatial layout of retinal ganglion cell receptive fields in the retina. The predictions of this model are borne out in four different species.

Analysis of mitochondrial replacement therapy shows, even with efficient mutant mitochondrial DNA replacement and maintenance in embryonic stem cells, a gradual loss of donor mitochondrial DNA in some lines owing to a polymorphism in the D-loop, potentially causing preferential replication of specific mitochondrial DNA haplotypes.