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Metal carbenes are accessed using a metallaphotoredox platform that exploits iron carbene reactivity using readily available chemical feedstocks and α-elimination.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

A manufacturable platform for quantum computing with photons is introduced and a set of monolithically integrated silicon-photonics-based modules is benchmarked, demonstrating dual-rail photonic qubits with performance close to thresholds required for operation.

Recent studies revealed that G protein-coupled receptors rapidly interconvert between multiple states. Here, authors use the kappa opioid receptor (KOR) and show how two state-dependent nanobodies provide real-time reporting of ligand stabilized states with KOR and other GPCRs.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

A large-area fabrication approach to achieve three-dimensional architectured metamaterials, with structural features spanning seven orders of magnitude, results in advanced mechanical properties, including high elasticity.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

The complex band structure and carrier decay response upon photoexcitation of the chiral semiconductor tellurium remain to be unveiled. Here, the authors report unusual dynamic band modifications in Te near band-edge structure due to photoinduced symmetry breaking and strong anisotropy in carrier decay dynamics.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

Ageing increases the risk of many diseases. Here the authors compare blood cell transcriptomes of over 14,000 individuals and identify a set of about 1,500 genes that are differently expressed with age, shedding light on transcriptional programs linked to the ageing process and age-associated diseases.

In this alternative approach to quantum computation, the all-electrical operation of two qubits, each encoded in three physical solid-state spin qubits, realizes swap-based universal quantum logic in an extensible physical architecture.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

The GEMINI consortium sequenced 1,000 cases of idiopathic male infertility and identified a plausible Mendelian cause in 20% of cases. The infertility genes can be grouped by expression pattern, facilitating their interpretation and follow-up.

Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

Photoacoustic imaging offers higher spatial resolution than most optical imaging techniques, but contrast agents are needed because many diseases in their early stages do not display a natural photoacoustic contrast. Using single-walled carbon nanotubes conjugated with a peptide as a contrast agent allows the non-invasive photoacoustic imaging of tumours in animals.

Coupling advances in socioeconomic projections, climate models, damage functions and discounting methods yields an estimate of the social cost of carbon of US$185 per tonne of CO₂—triple the widely used value published by the US government.

White-tailed deer are a potential reservoir of SARS-CoV-2 variants.

The 1.8 Å high-resolution X-ray crystal structure of the human δ-opioid receptor is presented, with site-directed mutagenesis and functional studies revealing a crucial role for a sodium ion in mediating allosteric control in this receptor.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

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.

The contribution of astrocytic Ca²⁺ signaling to the modulation of sensory transmission in different brain states remains largely unknown. Here, the authors show two types of Ca²⁺ signals in the mouse barrel cortex with distinct function in sensory transmission during sleep and arousal states.

The SARS-CoV-2 variant expressing spike(D641G) shows increased infectivity in human lung epithelial cells and in hamster and primary human upper airway tissues, but is more susceptible to neutralization by antibodies raised against SARS-CoV-2.

During the Carboniferous–Permian transition, reduction of tropical wetlands accommodated emerging dryland-adapted amniote faunas from a western Pangaean epicentre.

IFN-λ has important innate immune system functions at mucosal surfaces, but its importance in adaptive immunity is largely unknown. Using an influenza infection model, Gale and colleagues demonstrate that IFN-λ is essential for effective adaptive cellular immunity in the lung.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

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.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

A monobody was identified that binds to an allosteric lobe at the α4-β6-α5 interface to block H- and K-RAS signaling and transformation by disrupting RAS dimerization and nanoclustering.

The crystal structure of the human κ-opioid receptor in complex with an antagonist, JDTic, is determined, with potential importance for the design of new therapeutic agents.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Antagonists of Smoothened, a class F GPCR involved in the hedgehog pathway, have been developed to treat some cancers. Here Wang et al.report structures of Smoothened in complex with antagonists and an agonist, and describe how mutations may result in resistance to anti-Smoothened treatment.

Highly selective activators of IRE1/XBP1 splicing pathway were identified via high-throughput screen, which promoted the degradation of APP and reduced APP-associated mitochondrial toxicity in an IRE1-dependent manner.

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a non-Hodgkin-type B cell lymphoma. Here, the authors identify two risk loci for WM/LPL in a two-stage GWAS involving a family-oversampling approach and provide evidence for a functional role of the non-coding SNP rs116446171.

Thompson and colleagues show that repetitive antigenic stimulation within the tumor environment triggers mitochondrial dysfunction by inhibiting oxidative phosphorylation, which leads to T cell exhaustion.

DNA sequencing of 3,864 individuals with ALS and 7,839 controls identified a novel disease gene, DNAJC7, which encodes a heat-shock protein. As DNAJC7 is an essential part of cell maintenance, mutations in DNAJC7 may lead to neurodegeneration.

Vicinity of small bodies might be dangerous to the spacecrafts and to their instrumentation. Here the authors show the operational environment of asteroid Bennu, validate its photometric phase function and demonstrate the accelerating rotational rate due to YORP effect using the data acquired during the approach phase of OSIRIS-REx mission.

Whether Alzheimer’s disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.