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

Specialised ribonucleoprotein (RNP) granules are a hallmark of polarized cells, like neurons and germ cells. Among their main functions is the spatial and temporal modulation of the activity of specific mRNA transcripts that allow specification of primary embryonic axes. While RNPs composition and role are well established, their regulation is poorly defined. Here, we demonstrate that Hecw, a newly

The Xanthomonas outer protein C2 (XopC2) family of bacterial effectors is widely found in plant pathogens and Legionella species. However, the biochemical activity and host targets of these effectors remain enigmatic. Here we show that ectopic expression of XopC2 promotes jasmonate signaling and stomatal opening in transgenic rice plants, which are more susceptible to Xanthomonas oryzae pv. oryzicola

By analyzing structural and electronic properties of more than a hundred predicted hydrogen-based superconductors, we determine that the capacity of creating an electronic bonding network between localized units is key to enhance the critical temperature in hydrogen-based superconductors. We define a magnitude named as the networking value, which correlates with the predicted critical temperature better

Natural observations suggest that in safe environments, organisms avoid competition to maximize gain, while in hazardous environments the most effective survival strategy is to congregate with competition to reduce the likelihood of predatory attack. We probed the extent to which survival decisions in humans follow these patterns, and examined the factors that determined individual-level decision-making

Evolutionary constraints may significantly bias phenotypic change, while “breaking” from such constraints can lead to expanded ecological opportunity. Ray-finned fishes have broken functional constraints by developing two jaws (oral-pharyngeal), decoupling prey capture (oral jaw) from processing (pharyngeal jaw). It is hypothesized that the oral and pharyngeal jaws represent independent evolutionary

Energy efficiency is motivating the search for new high-temperature (high-T) metals. Some new body-centered-cubic (BCC) random multicomponent “high-entropy alloys (HEAs)” based on refractory elements (Cr-Mo-Nb-Ta-V-W-Hf-Ti-Zr) possess exceptional strengths at high temperatures but the physical origins of this outstanding behavior are not known. Here we show, using integrated in-situ neutron-diffraction

Dual-energy X-ray absorptiometry (DXA) is underutilized to measure bone mineral density (BMD) and evaluate fracture risk. We present an automated tool to identify fractures, predict BMD, and evaluate fracture risk using plain radiographs. The tool performance is evaluated on 5164 and 18175 patients with pelvis/lumbar spine radiographs and Hologic DXA. The model is well calibrated with minimal bias

Sea spray aerosol (SSA) formation have a major role in the climate system, but measurements at a global-scale of this micro-scale process are highly challenging. We measured high-resolution temporal patterns of SSA number concentration over the Atlantic Ocean, Caribbean Sea, and the Pacific Ocean covering over 42,000 km. We discovered a ubiquitous 24-hour rhythm to the SSA number concentration, with

Intraspecific competition is a major force in mediating population dynamics, fuelling adaptation, and potentially leading to evolutionary diversification. Among the evolutionary arms races between parasites, one of the most fundamental and intriguing behavioural adaptations and counter-adaptations are superparasitism and superparasitism avoidance. However, the underlying mechanisms and ecological contexts

Implant related infections are the most common cause of joint arthroplasty failure, requiring revision surgeries and a new implant, resulting in a cost of $8.6 billion annually. To address this problem, we created a class of coating technology that is applied in the operating room, in a procedure that takes less than 10 min, and can incorporate any desired antibiotic. Our coating technology uses an

Magic-angle twisted bilayer graphene has recently become a thriving material platform realizing correlated electron phenomena taking place within its topological flat bands. Several numerical and analytical methods have been applied to understand the correlated phases therein, revealing some similarity with the quantum Hall physics. In this work, we provide a Mott-Hubbard perspective for the TBG system

Expanding the chemical space for designing novel anionic redox materials from oxides to sulfides has enabled to better apprehend fundamental aspects dealing with cationic-anionic relative band positioning. Pursuing with chalcogenides, but deviating from cationic substitution, we here present another twist to our band positioning strategy that relies on mixed ligands with the synthesis of the Li2TiS3-xSex

Chromosomal instability (CIN) is a hallmark of cancer1. Yet, many childhood cancers, such as Ewing sarcoma (EwS), feature remarkably ‘silent’ genomes with minimal CIN2. Here, we show in the EwS model how uncoupling of mitosis and cytokinesis via targeting protein regulator of cytokinesis 1 (PRC1) or its activating polo-like kinase 1 (PLK1) can be employed to induce fatal genomic instability and tumor

A fundamental question in community ecology is the role of predator–prey interactions in food-web stability and species coexistence. Although microbial microcosms offer powerful systems to investigate it, interrogating the environment is much more arduous. Here, we show in a 1-year survey that the obligate predators Bdellovibrio and like organisms (BALOs) can regulate prey populations, possibly in

Treatment and prevention of human immunodeficiency virus type one (HIV-1) infection was transformed through widespread use of antiretroviral therapy (ART). However, ART has limitations in requiring life-long daily adherence. Such limitations have led to the creation of long-acting (LA) ART. While nucleoside reverse transcriptase inhibitors (NRTI) remain the ART backbone, to the best of our knowledge

Acetylcholine release in the hippocampus plays a central role in the formation of new memory representations. An influential but largely untested theory proposes that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3. Here, we show that excitatory inputs from entorhinal

Rotating cilia at the vertebrate left-right organizer (LRO) generate an asymmetric leftward flow, which is sensed by cells at the left LRO margin. Ciliary activity of the calcium channel Pkd2 is crucial for flow sensing. How this flow signal is further processed and relayed to the laterality-determining Nodal cascade in the left lateral plate mesoderm (LPM) is largely unknown. We previously showed

The control of light-matter interaction at the most elementary level has become an important resource for quantum technologies. Implementing such interfaces in the THz range remains an outstanding problem. Here, we couple a single electron trapped in a carbon nanotube quantum dot to a THz resonator. The resulting light-matter interaction reaches the deep strong coupling regime that induces a THz energy

Eukaryotic phytoplankton are responsible for at least 20% of annual global carbon fixation. Their diversity and activity are shaped by interactions with prokaryotes as part of complex microbiomes. Although differences in their local species diversity have been estimated, we still have a limited understanding of environmental conditions responsible for compositional differences between local species

To address the global water shortage crisis, one of the promising solutions is to collect freshwater from the environmental resources such as fog. However, the efficiency of conventional fog collectors remains low due to the viscous drag of fog-laden wind deflected around the collecting surface. Here, we show that the three-dimensional and centimetric kirigami structures can control the wind flow,

Numerous studies have focused on the need to expand production of ‘blue foods’, defined as aquatic foods captured or cultivated in marine and freshwater systems, to meet rising population- and income-driven demand. Here we analyze the roles of economic, demographic, and geographic factors and preferences in shaping blue food demand, using secondary data from FAO and The World Bank, parameters from

Topological photonics has revolutionized our understanding of light propagation, providing a robust way to manipulate light. So far, most of studies in this field are focused on designing a static photonic structure. Developing a dynamic photonic topological platform to switch multiple topological functionalities at ultrafast speed is still a great challenge. Here we theoretically propose and experimentally