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In many neurodegenerative disorders, the spread of protein aggregates underlies disease progression in the brain. A receptor molecule has now been found that mediates the neuronal uptake of one such harmful protein. See p.381

With ageing, normal human tissues experience an expansion of somatic clones that carry cancer mutations(1-7). However, whether such clonal expansion exists in the non-neoplastic intestine remains unknown. Here, using whole-exome sequencing data from 76 clonal human colon organoids, we identify a unique pattern of somatic mutagenesis in the inflamed epithelium of patients with ulcerative colitis. The affected epithelium accumulates somatic mutations in multiple genes that are related to IL-17 signalling-including NFKBIZ, ZC3H12A and PIGR, which are genes that are rarely affected in colon cancer. Targeted sequencing validates the pervasive spread of mutations that are related to IL-17 signalling. Unbiased CRISPR-based knockout screening in colon organoids reveals that the mutations confer resistance to the proapoptotic response that is induced by IL-17A. Some of these genetic mutations are known to exacerbate experimental colitis in mice(8-11), and somatic mutagenesis in human colon epithelium may be causally linked to the inflammatory process. Our findings highlight a genetic landscape that adapts to a hostile microenvironment, and demonstrate its potential contribution to the pathogenesis of ulcerative colitis.

Using annual projections of temperature and precipitation to estimate when species will be exposed to potentially harmful climate conditions reveals that disruption of ecological assemblages as a result of climate change will be abrupt and could start as early as the current decade.

A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world(1-3). Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor(4). Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses(1-3,5). The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.

When a magnetic impurity exists in a metal, conduction electrons form a spin cloud that screens the impurity spin. This basic phenomenon is called the Kondo effect(1,2). Unlike electric-charge screening, the spin-screening cloud(3-6) occurs quantum coherently, forming spin-singlet entanglement with the impurity. Although the spins interact locally around the impurity, the Kondo cloud can theoretically spread out over several micrometres. The cloud has not so far been detected, and so its physical existence-a fundamental aspect of the Kondo effect-remains controversial(7,8). Here we present experimental evidence of a Kondo cloud extending over a length of micrometres, comparable to the theoretical length xi(K). In our device, a Kondo impurity is formed in a quantum dot(2,9-11), coupling on one side to a quasi-one-dimensional channel(12) that houses a Fabry-Perot interferometer of various gate-defined lengths L exceeding one micrometre. When we sweep a voltage on the interferometer end gate-separated by L from the quantum dot-to induce Fabry-Perot oscillations in conductance we observe oscillations in the measured Kondo temperature T-K, which is a signature of the Kondo cloud at distance L. When L is less than xi(K) the T-K oscillation amplitude becomes larger as L becomes smaller, obeying a scaling function of a single parameter L/xi(K), whereas when L is greater than xi(K) the oscillation is much weaker. Our results reveal that xi(K) is the only length parameter associated with the Kondo effect, and that the cloud lies mostly within a length of xi(K). Our experimental method offers a way of detecting the spatial distribution of exotic non-Fermi liquids formed by multiple magnetic impurities or multiple screening channels(13-16) and of studying spin-correlated systems.