The catalytic asymmetric construction of Csp3–Csp3 bonds remains one of the foremost challenges in organic synthesis.1 Metal-catalyzed cross-electrophile couplings (XEC) have emerged as a powerful tool for C–C bond formation.2-5 However, coupling two distinct Csp3-electrophiles with high cross- and stereoselectivity continues as an unmet challenge. Here, we report a highly chemo- and enantioselective

Accurate and timely detection of recombinant lineages is crucial for interpreting genetic variation, reconstructing epidemic spread, identifying selection and variants of interest, and accurately performing phylogenetic analyses 1–4. During the SARS-CoV-2 pandemic, genomic data generation has exceeded the capacities of existing analysis platforms, thereby crippling real-time analysis of viral evolution

The SARS-CoV-2 Delta variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. Delta’s emergence in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 virus genomes from England together with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction

Direct molecular editing of heteroarene carbon-hydrogen (C–H) bonds through consecutive selective C–H functionalization has the potential to grant rapid access into diverse chemical space; a valuable but often challenging venture to achieve in medicinal chemistry1. Contrasting with electronically-biased heterocyclic C–H bonds2-9, remote benzocyclic C–H bonds on bicyclic aza-arenes are especially difficult

The SARS-CoV-2 RNA genome contains a 5′-cap that facilitates translation of viral proteins, protection from exonucleases and evasion of the host immune response1-4. How this cap is made in SARS-CoV-2 is not completely understood. Here, we reconstitute the SARS-CoV-2 7MeGpppA2′-O-Me-RNA cap using virally encoded non-structural proteins (nsps). We show that the kinase-like NiRAN domain5 of nsp12 transfers

Thyroid hormones are vital to metabolism, growth and development1. Thyroid hormone synthesis is controlled by thyrotropin (TSH), which acts at the thyrotropin receptor (TSHR)2. Autoantibodies that activate the TSHR pathologically increase thyroid hormones in Graves’ disease3. How autoantibodies mimic TSH function remains unclear. We determined cryogenic-electron microscopy structures of active and

On the evening of 15 January 2022, the Hunga Tonga-Hunga Ha’apai volcano1 unleashed a violent underwater eruption, blanketing the surrounding land masses in ash and debris2, 3. The eruption generated tsunamis observed around the world. An event of this type last occurred in 1883 during the eruption of Krakatau4, and thus we have the first observations of a tsunami from a large emergent volcanic eruption

Thyroid stimulating hormone (TSH), through activation of its G protein-coupled thyrotropin receptor (TSHR), controls the synthesis of thyroid hormone (TH), an essential metabolic hormone1-3. Aberrant signaling of TSHR by autoantibodies causes Graves’ disease and hypothyroidism that affect millions of patients worldwide4. Here we report the active structures of TSHR with TSH and an activating autoantibody

Identifying the factors underlying severe COVID-19 in the host genetics is an emerging issue1–5. We conducted a genome-wide association study (GWAS) involving 2,393 Japanese COVID-19 cases collected in initial pandemic waves with 3,289 controls, which identified a variant on 5q35 (rs60200309-A) near DOCK2 associated with severe COVID-19 in younger (<65 ages) patients (nCase=440, odds ratio=2.01, P=1

Highly pathogenic coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2, Middle East respiratory syndrome coronavirus (MERS-CoV)3, and SARS-CoV-14 vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5-7 and in patient tissues8-10, suggesting a potential link between apoptosis and

Polar auxin transport (PAT) is unique to plants and coordinates their growth and development1,2. The PIN-FORMED (PIN) auxin transporters with remarkable asymmetrical localizations at the plasma membrane drive PAT3,4, however, their structures and transport mechanisms remain largely unknown. Here, we report three inward-facing conformation structures of the major member of the PIN family, PIN1 in Arabidopsis

The PIN-FORMED (PIN) protein family of auxin transporters mediates the polar auxin transport and plays crucial roles in plant growth and development1,2. Here we present cryo-EM structures of PIN3 from Arabidopsis thaliana (AtPIN3) in the apo state and in complex with its substrate indole-3-acetic acid (IAA) and the inhibitor N-1-naphthylphthalamic acid (NPA) at 2.6–3.0 Å resolution. AtPIN3 exists as

Digital logic circuits are based on complementary pairs of n- and p-type field effect transistors (FETs) via complementary metal oxide semiconductor (CMOS) technology. In three dimensional (3D or bulk) semiconductors, substitutional doping of acceptor or donor impurities is used to achieve p- and n-type FETs. However, the controllable p-type doping of low-dimensional semiconductors such as two-dimensional

Anorexia and fasting are host adaptations to acute infection, inducing a metabolic switch towards ketogenesis and the production of ketone bodies, including β-hydroxybutyrate (BHB) 1-6. However, whether ketogenesis metabolically influences the immune response in pulmonary infections remains unclear. Here we report impaired production of BHB in humans with SARS-CoV-2-induced but not influenza-induced

Single atoms or ions on surfaces affect processes from nucleation1 to electrochemical reactions2 and heterogeneous catalysis3. Transmission electron microscopy (TEM) is a leading approach for visualizing single atoms on a variety of substrates4,5. It conventionally requires high vacuum conditions, but has been developed for in situ imaging in liquid and gaseous environments6,7 with a combined spatial