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KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

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.

This study releases a very high-resolution migration dataset that reveals trends that shape daily life: rising moves into high-income neighborhoods, racial gaps in upward mobility, and wildfire-driven moves.

In this study, Dahmane et al use a method called cryo-electron tomography to uncover new details of how tick-borne flaviviruses transform cells into virus factories.

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.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

Short-circuiting during fast charging through lithium dendrite intrusion into electrolytes is a major challenge in solid-state batteries. Here, using thermally annealed 3-nm-thick Ag coatings, lithium penetration into brittle electrolyte Li_6.6La₃Zr_1.6Ta_0.4O₁₂ is inhibited at local current densities of 250 mA cm⁻² due to an increase in surface fracture toughness.

Pertpy serves as a one-stop and performant framework for single-cell perturbation data analysis.

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.

Instabilities in chiral plasmas can amplify electromagnetic waves, raising the question of whether chiral solids behave similarly. Now a magneto-chiral instability is demonstrated in tellurium, observed as growing terahertz emission after photoexcitation.

Coordinated gene segment rearrangement across a long genomic distance is essential for antibody gene production, but how this is regulated at the chromatin level is still unclear. Here the authors show that an architectural protein, CTCF, modulates both chromatin loop extrusion and diffusion to enforce diverse Vκ gene segment utilization for a diverse Igκ repertoire.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

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 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.

Moiré superlattices offer a tunable platform for studying charge and spin phenomena in correlated solid-state systems. Here, the authors explore spin transport in twisted WSe₂/WS₂ superlattices and find signatures of spin–charge transport decoupling.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

Laryngeal echolocation occurs in two separate groups of bats, so it is not clear if this is an example of convergent evolution or if those bats that cannot echolocate previously lost the ability. Here, a study of cochlear development in bats and other mammals supports a single origin of echolocation.

Many premalignant colorectal polyps in familial adenomatous polyposis arise polyclonally rather than from a single mutated cell, showing diverse early evolutionary trajectories that frequently occur without clonal APC or KRAS driver events.

Scaling Si spin qubits relies on the uniform control of qubit-host interactions. This work finds correlations in qubit energy levels across a manufactured device arising from placement of Ge in the quantum well, consistent with atomistic modeling.

A key challenge for compact accelerators is boosting an electron beam’s energy without

sacrificing its brightness. Here, the authors demonstrate the concept of a plasma wakefield

‘dual transformer’, which simultaneously increases both beam energy and brightness of an

electron bunch injected from the plasma at SLAC.

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.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

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.

Circulating tumor cell (CTC) clusters are much more likely to produce viable metastasis than single CTCs. Here the authors find that the transmembrane protein Plexin-B2 (PLXNB2) mediates homotypic and heterotypic CTC cluster formation, driving lung metastasis in breast cancer mouse models.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

Neuroinflammation following intracortical microelectrode implantation impairs long-term brain-machine interface performance. Here, the authors developed a nanoparticle-based therapy that improves local hemostasis and delivers dexamethasone, reducing inflammation.

The clinical outcomes of esophageal squamous cell carcinoma (ESCC) remain poor, and thus it remains critical to find prognostic molecular markers. Here, the authors identify prognostic ESCC subtypes based on bulk and single-cell RNA-seq combined with histology AI in samples from patients with more than four years of follow-up, and find markers associated with immune evasion.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

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.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

A graph neural network framework enables individualized genetic risk prediction at the single-cell level.

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.

Nature catches up with some past fraud investigations — and finds that, whether researchers are found to be guilty or innocent, the wounds are slow to heal.

Banerjee et al. report that the Vps13-like lipid transport protein BLTP2 regulates plasma membrane fluidity by maintaining phosphatidylethanolamine homeostasis. BLTP2 also facilitates breast cancer cell growth, suggesting a separate role in tumorigenesis.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

The current crisis in worldwide food prices reinforces the need for more productive agriculture. Emma Marris meets five ambitious scientists determined to stop the world from going hungry.

Genome-wide sgRNA libraries based on rules for on-target activity improve results of Cas9-based screens and facilitate a further refinement of on- and off-target prediction algorithms.

Integrated structural biology approach leveraging in situ cryo-electron tomography reveals molecular details of the native malarial translation elongation cycle and its perturbation by cabamiquine, a potent antimalarial drug candidate.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Youti yuanshi is a euarthropod species newly described from a fossilized larva from Yunnan Province, China dating approximately to late Atdabanian stage, Cambrian period, and provides insights into the evolution of arthropods.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.