Search

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Here, the authors develop novel dynamical methods to model brain regions’ intrinsic neural timescales (INTs) from data, and find that they couple whole-brain structural connectivity to dynamic switching between brain activity states, and correlate with genetic markers.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

Human and rodent supragranular pyramidal neurons differ in HCN channel-related properties. Comparison across primates reveals robust HCN1 expression and HCN channel-dependent physiology, with cell type dependent differences in macaques versus humans.

Longitudinal cerebrospinal fluid proteomics in multiple sclerosis uncovers dynamic antiviral immune activity, sex-based differences in damage and repair, and evolving myeloid-stromal cell interactions that correlate with disability development.

The authors mapped the dendritic morphology of thousands of striatal D1-type and D2-type medium spiny neurons in healthy and Huntington’s disease mouse brains, revealing dendritic modules with distinct neuronal shapes, spatial distributions and cortical inputs.

The authors previously pinpointed OLAH (oleoyl-ACP-hydrolase) as a driver of life-threatening viral diseases. Here, the authors identify increased IL-18Rα expression on CD8⁺ T cells, which acquire a reduced cytotoxic signature, correlates with severe respiratory viral infection of influenza A virus, RSV and COVID-19.

Confocal Airy beam integrated with single-photon oblique light-sheet tomography (CAB-OLST) is a high-throughput imaging approach for brain-wide mapping of neurons, as demonstrated in cleared mouse brains.

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.

RFdiffusion2, an extension of the RFdiffusion framework, builds de novo enzyme active sites using atom-level functional group constraints.

The textile industry’s reliance on synthetic dyes is an important source of greenhouse gas emissions. Here the authors describe a process involving sustainable solvents that allows the extraction, purification, and reuse of dyes, as well as the recycling of dye-free fabrics.

Pcm1 bridges centrosome asymmetry and polarized endosome trafficking to regulate radial glia progenitor fate decisions, balancing self-renewal and differentiation in zebrafish and human cortical organoids.

Tangram is a versatile tool for aligning single-cell and single-nucleus RNA-seq data to spatially resolved transcriptomics data using deep learning.

The protein p53 responds to DNA damage and intracellular infection by activating pathways that arrest the cell cycle, repair DNA, and elicit apoptosis. Here, Allen et al. show that the obligate intracellular bacterium Orientia tsutsugamushi inhibits p53 expression and protects host cells from DNA damage, thus delaying apoptosis and favouring bacterial replication.

A generative artificial intelligence-powered method enables de novo design of highly active enzymes based on information about the geometry of residues in the active site, without requiring protein backbone or sequence information.

A complementary metal–oxide–semiconductor (CMOS) imager that has a 512-pixel silicon image sensor post-processed into a 4.1-mm-long, 120-μm-wide shank with a collinear fibre for illumination can be used to record transient fluorescent signals in deep brain regions at 400 frames per second.

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.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

Here, the authors systematically interrogate the impact of acute stress on the sexually-dimorphic ventral subiculum circuitry and identify sex-specific synaptic and behavioral adaptations. Critically, these sex-specific adaptations are driven by distinct signaling pathways.

Combining brain imaging, genetics and behavioral data, this study shows that distinct brainwide distributions of serotonin receptors explain the known division of serotonin effects on human impulsivity and aversive processing.

The mechanisms underlying neuron specification and maturation are unclear. Here the authors provide an integrated epigenomic and transcriptomic analysis of mouse and marmoset neocortical neuronal classes. Pan-neuronal programs active during early development are more evolutionary conserved but not neuron-specific, whereas pan-neuronal programs active during later stages of maturation are more neuron- and species-specific.

¹³⁴Ce and ¹³⁴La have great potential as companion diagnostic isotopes for radiotherapeutics labelled with α-emitting ²²⁵Ac and ²²⁷Th. Now, by controlling the Ce^III/Ce^IV redox couple, the large-scale production, purification and characterization of ¹³⁴Ce- and ¹³⁴La-based radiolabels has been achieved and their use for in vivo positron emission tomography is demonstrated.

Transferrin receptor (TfR) and CD98hc are increasingly used to enable more effective drug delivery to the central nervous system. Here, the authors reveal comprehensive and distinct brain cellular and whole body biodistribution patterns of TfR- and CD98hc-binding molecules.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

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.

The collapse of tropical forests during the Permian–Triassic Mass Extinction weakened carbon sequestration, sustaining high CO2 and extreme global warmth for millions of years: an example of a runaway feedback in Earth’s climate-carbon system.

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.

Enzymatic recycling is an emerging technology to circularize the ubiquitous polyester poly(ethylene terephthalate). Here the authors evaluate and implement multiple process changes to improve the scalability and viability of this recycling technology. Process modeling demonstrates that these changes could enable cost competitiveness and greatly reduce overall life cycle impacts.

CD388 is a first-in-class antiviral drug–Fc conjugate engineered for extended half-life that demonstrates potent prophylactic and therapeutic efficacy against lethal influenza A and B challenge in mice.

Current cell annotation methods using high-plex spatial proteomics data are resource intensive and demand iterative expert input. Here, the authors present MAPS (Machine learning for Analysis of Proteomics in Spatial biology), an approach that facilitates rapid and precise cell type identification with human-level accuracy from spatial proteomics data.

A lightweight three-photon miniature microscope allows imaging neuronal activity throughout the cortex in freely moving mice.

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

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.

Selective neurodegeneration is a critical causal factor in Alzheimer’s disease. Zalocusky et al. demonstrate a causal chain linking neuronal ApoE expression to MHC-I expression and, subsequently, to tau pathology and selective neurodegeneration.

Viruses and bacteria are known to subvert the immune system using mimic or inhibitory proteins. Here the authors show that the protein Ank5 from the bacterium Orientia tsutsugamushi inhibits nuclear translocation and promotes proteasomal degradation of the MHC class I gene transactivator NLRC5.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

Inflammatory bowel diseases (IBD) are associated with increased faecal N-acylethanolamines (NAEs), which are primarily host-produced signalling lipids, in patients and a mouse model of colitis. These metabolites can enhance the growth of bacterial species enriched in IBD faecal samples and are associated with the expression of respiratory chain genes necessary for microbial metabolism of NAEs.

The understanding of defects in bromide-based perovskites remains elusive. Electric biasing and introducing bromide in the precursor solution during crystal growth is shown to significantly reduce defects in formamidinium lead bromide.