As the SARS-CoV-2 pandemic evolves, new variants continue to emerge. Some highly transmissible variants, such as Delta, also raised concerns about the effectiveness provided by current vaccines. Understanding immunological correlates of protection and how laboratory findings correspond to clinical effectiveness is imperative to shape future vaccination strategies.

Rhinoceroses are facing an uncertain future due to human-induced population-size reductions. In this issue of Cell, Liu et al. analyze rhinoceros genomes to study their past and find support for an early divergence between African and Asian species, signatures of past hybridization, and evidence of loss of genetic diversity.

Centromeres are specialized regions on chromosomes recruiting a set of proteins required for faithful chromosome segregation. Differences in centromere strength can potentially bias chromosome segregation toward one of the daughter cells during division. Kumon et al. propose a new model of evolutionary impact on the balance of centromere strength.

Directed evolution of AAV capsids has been a successful strategy for generating bespoke serotypes to target gene therapies more specifically to the intended tissue. This has now been achieved for the largest organ, skeletal muscle, by selecting for an RGD containing integrin binding heptamer in a hypervariable region of the capsid of AAV9.

Since the first reports of a novel severe acute respiratory syndrome (SARS)-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population. Recent debate has coalesced around two competing ideas: a “laboratory escape” scenario and zoonotic emergence. Here, we critically

The hidden world of amyloid biology has suddenly snapped into atomic-level focus, revealing over 80 amyloid protein fibrils, both pathogenic and functional. Unlike globular proteins, amyloid proteins flatten and stack into unbranched fibrils. Stranger still, a single protein sequence can adopt wildly different two-dimensional conformations, yielding distinct fibril polymorphs. Thus, an amyloid protein

A bank of 59 well-characterised prostate cancer patient-derived xenografts was established, including 17 classed as research-ready covering the disease-spectrum which, plus associated resources (organoids, serum, DNA/RNA profiles, tissue), are available for collaborative projects. This eagerly-anticipated resource will facilitate pre-clinical prostate cancer therapy studies.

The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte

Traditional 3D printing based on Digital Light Processing Stereolithography (DLP-SL) is unnecessarily limiting as applied to microfluidic device fabrication, especially for high-resolution features. This limitation is due primarily to inherent tradeoffs between layer thickness, exposure time, material strength, and optical penetration that can be impossible to satisfy for microfluidic features. We

The maintenance of genomic stability requires the coordination of multiple cellular tasks upon the appearance of DNA lesions. RNA editing, the post-transcriptional sequence alteration of RNA, has a profound effect on cell homeostasis, but its implication in the response to DNA damage was not previously explored. Here we show that, in response to DNA breaks, an overall change of the Adenosine-to-Inosine

Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells in vivo, leading to discoveries that may not be translated to the clinic. Intestinal organoids are increasingly used to model human disease and are amenable to genetic engineering

Application of an electric stimulus to a material with a metal-insulator transition can trigger a large resistance change. Resistive switching from an insulating into a metallic phase, which typically occurs by the formation of a conducting filament parallel to the current flow, is a highly active research topic. Using the magneto-optical Kerr imaging, we found that the opposite type of resistive switching

Valley anisotropy is a favorable electronic structure feature that could be utilized for good thermoelectric performance. Here, taking advantage of the single anisotropic Fermi pocket in p-type Mg3Sb2, a feasible strategy utilizing the valley anisotropy to enhance the thermoelectric power factor is demonstrated by synergistic studies on both single crystals and textured polycrystalline samples. Compared

Macromolecular dynamics manifest as disorder in structure determination, which is subsequently accounted for by displacement parameters (also called temperature factors, or B-factors) or alternate conformations. Though B-factors contain detailed information about structural dynamics, they are the total of multiple sources of disorder, making them difficult to interpret and thus little-used in structural

The incorporation of orthophosphate from scarce geochemical sources into the organic compounds essential for life under mild conditions is a fundamental challenge for prebiotic chemistry. Here we report a prebiotic system capable of overcoming this challenge by taking inspiration from extant life’s recycling of orthophosphate via its conversion into kinetically stable thermodynamically activated (KSTA)

Monolayer transition-metal dichalcogenides (TMDCs) show a wealth of exciton physics. Here, we report the existence of a new excitonic species, the high-lying exciton (HX), in single-layer WSe2 with an energy of ~3.4 eV, almost twice the band-edge A-exciton energy, with a linewidth as narrow as 5.8 meV. The HX is populated through momentum-selective optical excitation in the K-valleys and is identified

RNA polymerase inhibition plays an important role in the regulation of transcription in response to environmental changes and in the virus-host relationship. Here we present the high-resolution structures of two such RNAP-inhibitor complexes that provide the structural bases underlying RNAP inhibition in archaea. The Acidianus two-tailed virus encodes the RIP factor that binds inside the DNA-binding

Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the

Early transitional metal carbides are promising catalysts for hydrogenation of CO2. Here, a two-dimensional (2D) multilayered 2D-Mo2C material is prepared from Mo2CTx of the MXene family. Surface termination groups Tx (O, OH, and F) are reductively de-functionalized in Mo2CTx (500 °C, pure H2) avoiding the formation of a 3D carbide structure. CO2 hydrogenation studies show that the activity and product

Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus placebo that was conducted in 100 subjects with fatty

Under the Baltimore nucleic acid-based virus classification scheme, the herpesvirus human cytomegalovirus (HCMV) is a Class I virus, meaning that it contains a double-stranded DNA genome—and no RNA. Here, we report sub-particle cryoEM reconstructions of HCMV virions at 2.9 Å resolution revealing structures resembling non-coding transfer RNAs (tRNAs) associated with the virion’s capsid-bound tegument

Soluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) in human. It is an important validated drug target for cardiovascular diseases. sGC can be pharmacologically activated by stimulators and activators. However, the detailed structural mechanisms, through which sGC is recognized and positively modulated by these drugs at high spacial resolution, are poorly understood. Here, we present

PTEN promoter hypermethylation is nearly universal and PTEN copy number loss occurs in ~25% of fusion-negative rhabdomyosarcoma (FN-RMS). Here we show Pten deletion in a mouse model of FN-RMS results in less differentiated tumors more closely resembling human embryonal RMS. PTEN loss activated the PI3K pathway but did not increase mTOR activity. In wild-type tumors, PTEN was expressed in the nucleus

Antibody engineering technologies face increasing demands for speed, reliability and scale. We develop CeVICA, a cell-free nanobody engineering platform that uses ribosome display for in vitro selection of nanobodies from a library of 1011 randomized sequences. We apply CeVICA to engineer nanobodies against the Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein and identify >800 binder families

Recruitment of RNA polymerase and initiation factors to the promoter is the only known target for transcription activation and repression in archaea. Whether any of the subsequent steps towards productive transcription elongation are involved in regulation is not known. We characterised how the basal transcription machinery is distributed along genes in the archaeon Saccharolobus solfataricus. We discovered

Natural killer (NK) cells exert critical roles in anti-tumor immunity but how their functions are regulated by epitranscriptional modification (e.g., N6-methyladenosine (m6A) methylation) is unclear. Here we report decreased expression of the m6A “writer” METTL3 in tumor-infiltrating NK cells, and a positive correlation between protein expression levels of METTL3 and effector molecules in NK cells

Porous electrodes with extraordinary capacitances in liquid electrolytes are oftentimes incompetent when gel electrolyte is applied because of the escalating ion diffusion limitations brought by the difficulties of infilling the pores of electrode with gels. As a result, porous electrodes usually exhibit lower capacitance in gel electrolytes than that in liquid electrolytes. Benefiting from the swift

Purely-organic clusterization‐triggered emission (CTE) has displayed promising abilities in bioimaging, chemical sensing, and multicolor luminescence. However, it remains absent in the field of circularly polarized luminescence (CPL) due to the difficulties in well-aligning the nonconventional luminogens. We report a case of CPL generated with CTE using the solid phase molecular self-assembly (SPMSA)

Harmful algal and bacterial blooms linked to deforestation, soil loss and global warming are increasingly frequent in lakes and rivers. We demonstrate that climate changes and deforestation can drive recurrent microbial blooms, inhibiting the recovery of freshwater ecosystems for hundreds of millennia. From the stratigraphic successions of the Sydney Basin, Australia, our fossil, sedimentary and geochemical

Since the variables inherent to various diseases cannot be controlled directly in humans, behavioral dysfunctions have been examined in model organisms, leading to better understanding their underlying mechanisms. However, because the spatial and temporal scales of animal locomotion vary widely among species, conventional statistical analyses cannot be used to discover knowledge from the locomotion

Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated

Human shelterin components POT1 and TPP1 form a stable heterodimer that protects telomere ends from ATR-dependent DNA damage responses and regulates telomerase-dependent telomere extension. Mice possess two functionally distinct POT1 proteins. POT1a represses ATR/CHK1 DNA damage responses and the alternative non-homologous end-joining DNA repair pathway while POT1b regulates C-strand resection and

Wear-related energy and material loss cost over 2500 Billion Euro per year. Traditional wisdom suggests that high-strength materials reveal low wear rates, yet, their plastic deformation mechanisms also influence their wear performance. High strength and homogeneous deformation behavior, which allow accommodating plastic strain without cracking or localized brittle fracture, are crucial for developing

Phycobilisomes (PBS) are the major light-harvesting machineries for photosynthesis in cyanobacteria and red algae and they have a hierarchical structure of a core and peripheral rods, with both consisting of phycobiliproteins and linker proteins. Here we report the cryo-EM structures of PBS from two cyanobacterial species, Anabaena 7120 and Synechococcus 7002. Both PBS are hemidiscoidal in shape and

Perilla is a young allotetraploid Lamiaceae species widely used in East Asia as herb and oil plant. Here, we report the high-quality, chromosome-scale genomes of the tetraploid (Perilla frutescens) and the AA diploid progenitor (Perilla citriodora). Comparative analyses suggest post Neolithic allotetraploidization within 10,000 years, and nucleotide mutation in tetraploid is 10% more than in diploid

Basaltic crystal cargoes often preserve records of mantle-derived chemical variability that have been erased from their carrier liquids by magma mixing. However, the consequences of mixing between similarly primitive but otherwise chemically variable magmas remain poorly understood despite ubiquitous evidence of chemical variability in primary melt compositions and mixing-induced disequilibrium within

Sessile plants encode a large number of small peptides and cell surface-resident receptor kinases, most of which have unknown functions. Here, we report that the Arabidopsis receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2) recognizes the conserved signature motif of SERINE-RICH ENDOGENOUS PEPTIDEs (SCOOPs) from Brassicaceae plants as well as proteins present in fungal Fusarium

Fibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different

Understanding the atomic structure and structural instability of organic-inorganic hybrid perovskites is the key to appreciate their remarkable photoelectric properties and understand failure mechanism. Here, using low-dose imaging technique by direct-detection electron-counting camera in a transmission electron microscope, we investigate the atomic structure and decomposition pathway of CH3NH3PbI3

Science, Volume 373, Issue 6561, Page 1319-1321, September 2021.

Science, Volume 373, Issue 6561, Page 1312-1314, September 2021.

Science, Volume 373, Issue 6561, Page 1285-1285, September 2021.

Science, Volume 373, Issue 6561, Page 1298-1299, September 2021.

Science, Volume 373, Issue 6561, Page 1300-1303, September 2021.

Science, Volume 373, Issue 6561, Page 1299-1299, September 2021.

Science, Volume 373, Issue 6561, Page 1297-1297, September 2021.

Science, Volume 373, Issue 6561, Page 1296-1297, September 2021.