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Rai et al. report that CAMSAPs can bind to minus ends of microtubules attached to γ-tubulin ring complex (γ-TuRC) and drive microtubule release. They show that CDK5RAP2, but not CLASP2, inhibits CAMSAP-mediated microtubule release from γ-TuRC.

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.

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

Glucocorticoid receptor (GR) agonists - used in the treatment of solid malignant tumors to reduce inflammation - could potentially affect the anti-tumor activity of chemotherapy. Here, the authors identify a mechanism of cisplatin resistance observed with GR agonist treatment, and show the binding and activation of GR by cisplatin, which leads to MAST1 activation and subsequent MAPK re-activation.

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. Here the authors demonstrate that hematopoietic stem cells with short telomeres induced by mutations affecting telomerase complex genes undergo differentiation towards megakaryopoiesis through the activation of the IFI16-mediated interferon response.

Metabolomic profiling identified widespread adrenal insufficiency in patients with asthma receiving inhaled corticosteroids, which is a mainstay of asthma treatment, arguing for the need for regular monitoring of such patients to avoid adverse effects of adrenal suppression.

Dysregulated phosphorylation is well-known in cancers, but it has largely been studied in isolation from mutations. Here the authors introduce HotPho, a tool that can discover spatial interactions between phosphosites and mutations, which are associated with activating mutation and genetic dependencies in cancer.

Protein immunofluorescence imaging and affinity purification–mass spectrometry are combined to create a unified map of human cell architecture across scales, which the authors call the multi-scale integrated cell (MuSIC).

The systemic immune features that distinguish COVID-19 from common infections remain incompletely elucidated. Here McClain et al. compare RNA sequencing in peripheral blood between subjects with SARS-CoV-2 and other respiratory infections and demonstrate dysregulated immune responses in COVID-19 with both heterogeneous and conserved components.

Quantum supremacy is demonstrated using a programmable superconducting processor known as Sycamore, taking approximately 200 seconds to sample one instance of a quantum circuit a million times, which would take a state-of-the-art supercomputer around ten thousand years to compute.

Deforestation causes elevation-dependent warming over tropical mountain regions, according to high-resolution climate simulations.

Patients with BRAF^V600E-mutated colorectal cancer have encouraging overall response rates to inhibition of PD-1, BRAF and MEK, with translational analyses suggesting that induction of tumor-intrinsic programs and immune programs contributes to improved outcomes via MAPK inhibition.

ProBDNF can have drastic effects on synaptic function that are quite different from those of mature BDNF. It is, however, controversial whether proBDNF is ever released in amounts that are sufficient to affect normal synaptic plasticity. Here, Yang and colleagues have detected the release of proBDNF from hippocampal neurons using newly developed knock-in mice and antibodies.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

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.

An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Relevant features of T cell repertoire in human cancer remain to be delineated. Here the authors show, by TCR sequencing in a large cohort of lung cancer patients, that while a majority of T cell clones are shared between tumor and adjacent lung tissue, less frequent tumor-unique T cell clones correlate with worse prognosis.

The Sonic Hedgehog subgroup of medulloblastoma are characterised by the high infiltration of tumour-associated macrophages (TAMs). Here, the authors show that TAM numbers in patients are associated with better prognosis and that, consistently, in a murine model of medulloblastoma, these TAMs have anti-tumoural properties.

Nature’s oxygen-evolving complex of photosystem II is a multinuclear manganese cluster. Whether mononuclear manganese can also efficiently catalyse water oxidation has been a long-standing question. Now, Li and co-workers show that single atoms of manganese can be anchored on nitrogen-doped graphene to catalyse the oxygen evolution reaction. Credit: Water image Frankie Angel / Alamy Stock Photo.

Sequence depth and read length determine the quality of genome assembly. Here, the authors leverage a set of PacBio reads to develop guidelines for sequencing and assembly of complex plant genomes in order to allocate finite resources using maize as an example.

Genomic analyses of major clades of huge phages sampled from across Earth’s ecosystems show that they have diverse genetic inventories, including a variety of CRISPR–Cas systems and translation-relevant genes.

Hu, Tan, Chia et al. identify negative elongation factor A as one of the earliest drivers of the mouse embryonic 2-cell-like state through interaction with Top2a, which mediates Dux expression.

The dearth of glioblastoma model systems that accurately recapitulate the disease remains a challenge. Here, the authors develop cancer avatars using genetically engineered human induced pluripotent cells.

Stress kinases are activated in peripheral ischemic tissues in the presence of vascular diseases. Here the authors show that inhibition of the neural JNK3 kinase improves recovery from hind limb ischemia in animals through activation of the transcription factors Egr1/Creb1 and upregulation of growth factors.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

Studies have shown that breast cancer prognosis is hereditary. Here the authors show that a genetic variant in CCL20, a chemokine ligand involved in immune response, is significantly associated with breast cancer survival and may therefore represent an important therapeutic or prognostic target.

Massively parallel DNA sequencing allows entire genomes to be screened for genetic changes associated with tumour progression. Here, the genomes of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer were analysed. The samples came from peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The findings indicate that cells with a distinct subset of the primary tumour mutation might be selected during metastasis and xenografting.

Patient-derived xenografts recapitulate major genomic signatures and transcriptome profiles of their original tumours. Here, the authors, performing proteomic and phosphoproteomic analyses of 24 breast cancer PDX models, demonstrate that druggable candidates can be identified based on a comprehensive proteogenomic profiling.

Analysis of 60 sites in three ocean basins suggests that overgrowth of fleshy algae on coral reefs supports higher microbial abundances dominated by copiotrophic, potentially pathogenic bacteria via the provision of dissolved inorganic carbon.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Insulin therapies for patients with diabetes have challenges, including diminished hepatic preference of insulin action compared with endogenous insulin. Here the authors characterize insulin dimers that function as insulin receptor partial agonists, and exhibit hepatic and adipose tissue preference of insulin action and metabolic benefits in preclinical models.

An ultra-high-throughput multiplex protein–DNA binding assay is used to assess binding of 270 human transcription factors to 95,886 noncoding variants in the human genome, providing data to improve prediction of the effects of noncoding variants on transcription factor binding and thereby increase understanding of molecular pathways involved in diverse human traits and genetic diseases.

The female reproductive tract constitutes the ovary, fallopian tubes, uterus, and cervix, but it is challenging to engineer this systemin vitro. Here, the authors develop a microfluidic device (EVATAR) with reproductive tract and peripheral tissues to replicate hormone release of a 28-day menstrual cycle.

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.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

Here, the authors assess performance and limitations to polygenic risk scores in different race/ethnic groups. They find that polygenic risk score performance improves with diverse training data, and a better understanding of varying genetic backgrounds, social and environmental factors, and gene-environment interactions, is needed to enhance PRS performance for all groups.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

Self-renewing cells play an important role in initiation, progression, and therapy resistance in glioblastoma. Here, the authors identify histone variant macroH2A2 as a regulator of chromatin organisation resulting in the suppression of transcriptional programs of self-renewal in glioblastoma.

A quantum error correction scheme is demonstrated in a system of superconducting qubits, and repeated quantum non-demolition measurements are used to track errors and reduce the failure rate; increasing the system size from five to nine qubits improves the failure rate further.

A digitized approach to adiabatic quantum computing, combining the generality of the adiabatic algorithm with the universality of the digital method, is implemented using a superconducting circuit to find the ground states of arbitrary Hamiltonians.

A universal set of logic gates in a superconducting quantum circuit is shown to have gate fidelities at the threshold for fault-tolerant quantum computing by the surface code approach, in which the quantum bits are distributed in an array of planar topology and have only nearest-neighbour couplings.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.