Search

Ambrosia artemisiifolia is an invasive weed and primary cause of pollen-induced hayfever. Here, the authors report its chromosome-level phased genome assembly, examine genome-wide variation among modern and historic accessions, and identify large haploblocks underling rapid adaptation.

Nicole Soranzo and colleagues report a meta-analysis of genome-wide association datasets identifying 22 associations to 8 clinically relevant hematological traits. They also identify a long-range haplotype at 12q24 that includes variants associated with platelet counts as well as coronary artery disease and shows evidence of a selective sweep in Europeans.

Multielectron quantum dots offer a promising platform for high-performance spin qubits; however, previous demonstrations have been limited to single-qubit operation. Here, the authors report a universal gate set and two-qubit Bell state tomography in a high-occupancy double quantum dot in silicon.

The app-based COVID Symptom Study was launched in Sweden in April 2020 to contribute to real-time COVID-19 surveillance using daily symptom reports from study participants. Here, the authors show how syndromic surveillance can be used to estimate regional COVID-19 prevalence and to predict later COVID-19 hospital admissions.

This study finds that CRISPR-knockout phenotypes from genome-wide screens systematically show increased similarity to knockouts of unrelated genomically proximal genes located on the same chromosome arm. Multiple lines of evidence suggest that this proximity bias is caused by telomeric truncations of chromosome arms and is consistent across cell types, labs and Cas9 delivery methods.

The authors cracked P2Y14’s “sweet tooth”: structures bound to UDP-glucose and MRS2905 decode hexose and uracil nucleotide selectivity. A bipartite binding pocket with distinct nucleotide and hexose subpockets divided by V93 enables rational therapeutic design.

Terrestrial ecosystem productivity is widely accepted to be nutrient limited. A series of standardized nutrient addition experiments, carried out on grasslands on five continents, suggests aboveground grassland productivity is commonly limited by multiple nutrients, including potassium and micronutrients.

Bacterial cell shape is dependent on the formation of the extracellular sugar polymer called peptidoglycan. Here the authors describe RodA-PBP2, the enzymatic core of the elongasome, which is the complex responsible peptidoglycan synthesis, and utilize an integrated approach to investigate the mechanism of peptidoglycan biosynthesis.

Systematic studies are needed to discover molecular determinants of blood brain barrier dysfunction in Alzheimer’s disease. This study identifies perturbed pericytic SMAD3-astrocytic VEGFA interactions as a potential driver of this dysfunction.

Silicon-based spin qubits are promising candidates for a scalable quantum computer. Here the authors demonstrate the violation of Bell’s inequality in gate-defined quantum dots in silicon, marking a significant advancement that showcases the maturity of this platform.

The authors present 7 cryo-EM structures of hallucinogenic and non-hallucinogenic compounds across multiple chemotypes bound to the 5-HT2A receptor, shedding light onto ligand specificity and signaling bias.

Through analyses of ancient and modern human genomes, the authors show that previously reported Holocene-era admixture has masked more than 50 historic hard sweeps in modern European genomes.

Eutrophication has been shown to weaken diversity-stability relationships in grasslands, but it is unclear whether the effect depends on scale. Analysing a globally distributed network of grassland sites, the authors show a positive role of beta diversity and spatial asynchrony as drivers of stability but find that nitrogen enrichment weakens the diversity-stability relationships at different spatial scales.

The genomic landscape of diffuse gliomas remains to be characterised. Here, the authors perform whole genome sequencing of 403 tumours and identify recurrent coding and non-coding genetic mutations, their associations with clinical outcomes and potential therapeutic targets.

δ-Opioid receptors (δOR) are promising targets for pain management with reduced side effects. Here, the authors use a structure-based approach to design and characterize C6-Quino, a selective δOR partial agonist, highlighting its potential therapeutic relevance.

Global control of a qubits using a single microwave field is a promising strategy for scalable quantum computing. Here the authors demonstrate individual addressability vial local electrodes and two-qubit gates in an array of Si quantum dot spin qubits dressed by a global microwave field and driven on-resonance.

Despite advances in GPCR structures and peptide design, creating high-affinity ligands remains a challenge. Here the authors develop a computational method, successfully identifying peptide-based molecules for KOR: their platform shows promise for streamlined GPCR ligand discovery.

Initialization and operation of spin qubits in silicon above 1 K reach fidelities sufficient for fault-tolerant operations at these temperatures.

Many neurotransmitters act on receptors coupled to GTP-binding G proteins. Here authors report the structure and activity of a mutant that locks the nucleotide-free and receptor-bound state of the G protein, leading to a rare neurological disorder.

Swapan Nath, Sang-Cheol Bae and colleagues report the results of a large-scale association study of systemic lupus erythematosus in individuals of Asian ancestry. They identify several new susceptibility loci and find enrichment for signals near genes implicated in B cell and T cell function.

Remotely sensed NDVI data and contemporary field data from 84 grasslands on 6 continents show increasing divergence in aboveground plant biomass between sites in different bioclimatic regions.

The cryo-EM structures of MRGPRX1–Gq complexes are reported, which revealed the activation and allosteric modulation mechanism of human MRGPRX1 receptor, which may enable the structure-based identification of novel analgesics.

For solid-state qubits, the material environment hosts sources of errors that vary in time and space. This systematic analysis of errors affecting high-fidelity two-qubit gates in silicon can inform the design of large-scale quantum computers.

Structural studies of the itch receptors MRGPRX2 and MRGPRX4 in complex with endogenous and synthetic ligands provide a basis for the development of therapeutic compounds for pain, itch and mast cell-mediated hypersensitivity.

Understanding the microscopic variability of CMOS spin qubits is crucial for developing scalable quantum processors. Here the authors report a combined experimental and numerical study of the effect of interface roughness on variability of quantum dot spin qubits formed at the Si/SiO₂ interface.

Here the authors assess neutralizing antibody (nAb) levels as correlate of protection in a monoclonal antibody prevention trial and a vaccine trial for COVID-19 and show that nAb titers correlate with clinical protection against COVID-19 supporting nAb titer as a surrogate endpoint for authorization of monoclonal antibodies.

High-performance all-electrical control is a prerequisite for scalable silicon quantum computing. The switchable interaction between spins and orbital motion of electrons in silicon quantum dots now enables the electrical control of a spin qubit with high fidelity and speed, without the need for integrating a micromagnet.

Active-state structures of the κ-opioid receptor in complexes with the G-protein heterotrimers G_i1, G_oA, G_z and G_g provide insights into the actions of hallucinogenic opioids and G-protein-coupling specificity at the κ-opioid receptor.

This comprehensive study of the most enigmatic serotonin receptor 5-HT_5AR includes lots of pharmacological investigations, inactive and active state structures with antagonist, partial agonist and full agonists. Also, a highly potent and selective antagonist was developed.

The mechanism of action of muscarinic receptor-based DREADDs, important chemogenetic tools in neuroscience and cellular signalling research, are described in molecular detail.

Quantum biological electron transfer has potential in diagnostic and therapeutic settings. Here the authors report the triggered apoptosis of cancer cells using electricical input to wirelessly induce redox interactions at bio-nanoantennae in proximity to cancer cells.

This study elucidates how long-range chromatin loops are altered during short- and long-term changes in neural activity, and analyzes the interplay between the 3D genome and the linear epigenome during activity-dependent transcriptional responses.

A NutNet global grassland study finds that leaf N, P and K consistently respond to soil nutrient additions, but leaf morphological traits, such as specific leaf area, are inconsistent indicators of anthropogenic perturbations.

Here, a cross of Plasmodium vivax malaria parasites links a chloroquine resistance (CQR) phenotype to a 76 kb region of chromosome 1 and greater expression of pvcrt, an ortholog of the Plasmodium falciparum CQR transporter gene.

It remains unclear whether exotic and native species are functionally different. Using a global grassland experiment, Seabloomet al. show that native and exotic species respond differently to two globally pervasive environmental changes, addition of mineral nutrients and alteration of herbivore density.

Analysis of 65 grasslands worldwide from the Nutrient Network experiment reveals that plant communities with higher α- and β-diversity have higher levels of ecosystem multifunctionality, and that this effect is amplified across scales.

Analysis of multi-year nutrient enrichment experiments carried out on 45 global grassland sites show that an addition of an increasing number of nutrients leads to a reduction in plant species diversity, and competition for multiple belowground resources promotes plant species diversity.

Recombinant T-cells receptors can redirect naïve T cells but often have low or uneven expression. Here, the authors model mutations in TCR constant domains to increase T cell receptor expression, assembly, and stability and generate bispecific molecules.

How corticostriatal connections of different pyramidal cell types are organized, particularly in convergent circuits, has not been evaluated in detail. Here, cell type-specific Cre-driver mice reveal that pyramidal tract-type corticostriatal projections, though broadly similar to intratelencephalic-type projections from the same cortical region, are generally more restricted and variable in their topographic termination patterns.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

Identifying regions of the human genome that have been subject to selection is key to understanding our evolution, and provides insights into the genetic basis of disease. However, important caveats require consideration when interpreting the results of attempts to identify selected regions.

The National Cancer Institute (NCI) Genomic Data Commons (GDC) contains more than 2.9 petabytes of genomic and associated clinical data from more than 60 NCI-funded and other contributed cancer genomics research projects. The GDC consists of five applications over a common data model and a common application programming interface.