Global S&T Development Trend Analysis Platform of Resources and Environment
Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways(1). Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development(2,3). However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomaldominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients'
Primate inferotemporal cortex contains a coarse map of object space consisting of four networks, identified using functional imaging, electrophysiology and deep networks.
The inferotemporal (IT) cortex is responsible for object recognition, but it is unclear how the representation of visual objects is organized in this part of the brain. Areas that are selective for categories such as faces, bodies, and scenes have been found(1-5), but large parts of IT cortex lack any known specialization, raising the question of what general principle governs IT organization. Here we used functional MRI, microstimulation, electrophysiology, and deep networks to investigate the organization of macaque IT cortex. We built a low-dimensional object space to describe general objects using a feedforward deep neural network trained on object classification(6). Responses of IT cells to a large set of objects revealed that single IT cells project incoming objects onto specific axes of this space. Anatomically, cells were clustered into four networks according to the first two components of their preferred axes, forming a map of object space. This map was repeated across three hierarchical stages of increasing view invariance, and cells that comprised these maps collectively harboured sufficient coding capacity to approximately reconstruct objects. These results provide a unified picture of IT organization in which category-selective regions are part of a coarse map of object space whose dimensions can be extracted from a deep network.
The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-2(1). This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection(2).Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manisjavanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.
Quantum computation requires many qubits that can be coherently controlled and coupled to each other(1). Qubits that are defined using lithographic techniques have been suggested to enable the development of scalable quantum systems because they can be implemented using semiconductor fabrication technology(2-5). However, leading solid-state approaches function only at temperatures below 100 millikelvin, where cooling power is extremely limited, and this severely affects the prospects of practical quantum computation. Recent studies of electron spins in silicon have made progress towards a platform that can be operated at higher temperatures by demonstrating long spin lifetimes(6), gate-based spin readout(7) and coherent single-spin control(8). However, a high-temperature two-qubit logic gate has not yet been demonstrated. Here we show that silicon quantum dots can have sufficient thermal robustness to enable the execution of a universal gate set at temperatures greater than one kelvin. We obtain single-qubit control via electron spin resonance and readout using Pauli spin blockade. In addition, we show individual coherent control of two qubits and measure single-qubit fidelities of up to 99.3 per cent. We demonstrate the tunability of the exchange interaction between the two spins from 0.5 to 18 megahertz and use it to execute coherent two-qubit controlled rotations. The demonstration of '
Most magmatism occurring on Earth is conventionally attributed to passive mantle upwelling at mid-ocean ridges, to slab devolatilization at subduction zones, or to mantle plumes. However, the widespread Cenozoic intraplate volcanism in northeast China(1-3) and the young petit-spot volcanoes(4-7) offshore of the Japan Trench cannot readily be associated with any of these mechanisms. In addition, the mantle beneath these types of volcanism is characterized by zones of anomalously low seismic velocity above and below the transition zone(8-12) (a mantle level located at depths between 410 and 660 kilometres). A comprehensive interpretation of these phenomena is lacking. Here we show that most (or possibly all) of the intraplate and petit-spot volcanism and low-velocity zones around the Japanese subduction zone can be explained by the Cenozoic interaction of the subducting Pacific slab with a hydrous mantle transition zone. Numerical modelling indicates that 0.2 to 0.3 weight per cent of water dissolved in mantle minerals that are driven out from the transition zone in response to subduction and retreat of a tectonic plate is sufficient to reproduce the observations. This suggests that a critical amount of water may have accumulated in the transition zone around this subduction zone, as well as in others of the Tethyan tectonic belt(13) that are characterized by intraplate or petit-spot volcanism and low-velocity zones in the underlying mantle.
The widespread intraplate volcanism in northeast China and the unusual '
Cancer develops through a process of somatic evolution(1,2). Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes(3). Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)(4), we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.