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10.1093/mnras/stz3223 | 82,990,974 | ABSTRACT We have conducted 19 state-of-the-art 3D core-collapse supernova simulations spanning a broad range of progenitor masses. This is the largest collection of sophisticated 3D supernova simulations ever performed. We have found that while the majority of these models explode, not all do, and that even models in t... | 10.1038/s41586-020-03059-w | The largest collection of full-physics 3D simulations published so far, describing the witnessed systematics with progenitor mass and initial core density structure |
10.1146/annurev-nucl-102115-044747 | 61,514,055 | Nonspherical mass motions are a generic feature of core-collapse supernovae, and hydrodynamic instabilities play a crucial role in the explosion mechanism. The first successful neutrino-driven explosions could be obtained with self-consistent, first-principles simulations in three spatial dimensions. But three-dimensio... | 10.1038/s41586-020-03059-w | A useful review of core-collapse systematics, with some insights into the possible effects of rapid rotation |
10.1093/mnrasl/sly059 | 82,992,108 | Abstract We study the final fate of a very massive star by performing full general relativistic (GR), three-dimensional (3D) simulation with three-flavour multi-energy neutrino transport. Utilizing a 70 solar mass zero-metallicity progenitor, we self-consistently follow the radiation-hydrodynamics from the onset of gra... | 10.1038/s41586-020-03059-w | An important study using a fully general-relativistic hydrodynamic and transport approach |
10.3847/1538-4357/aac2da | 103,795,070 | Abstract The density structure surrounding the iron core of a massive star when it dies is known to have a major effect on whether or not the star explodes. Here we repeat previous surveys of presupernova evolution with some important corrections to code physics and four to 10 times better mass resolution in each star.... | 10.1038/s41586-020-03059-w | An important source of 1D massive star progenitor models using a state-of-the-art stellar evolution code |
10.1126/science.aaw4913 | 123,045,860 | “Hidden phases” are metastable collective states of matter that are typically not accessible on equilibrium phase diagrams. These phases can host exotic properties in otherwise conventional materials and hence may enable novel functionality and applications, but their discovery and access are still in early stages. Usi... | 10.1038/s41563-022-01413-z | This report shows how resonant terahertz pulses can induce a transient polar displacement in SrTiO 3 |
10.1038/s41467-020-16912-3 | 81,756,458 | Abstract Advances in complex oxide heteroepitaxy have highlighted the enormous potential of utilizing strain engineering via lattice mismatch to control ferroelectricity in thin-film heterostructures. This approach, however, lacks the ability to produce large and continuously variable strain states, thus limiting the p... | 10.1038/s41563-022-01413-z | This article demonstrates how strain can be used to break symmetry and stabilize ferroelectricity in SrTiO 3 |
10.1126/science.aah5298 | 100,557,170 | A nonpathogenic virus can promote inflammatory immunity to dietary antigens and may be linked to the development of celiac disease. | 10.1038/s41575-018-0064-z | This study provides support for the concept that viruses can disrupt intestinal immune homeostasis and initiate loss of oral tolerance and T helper 1 cell immunity to dietary antigen |
10.1073/pnas.1412008111 | 104,437,689 | Significance The prevalence of food allergy is rising at an alarming rate; the US Centers for Disease Control and Prevention documented an 18% increase among children in the United States between 1997 and 2007. Twenty-first century environmental interventions are implicated by this dramatic generational increase. In th... | 10.1038/s41575-018-0064-z | In this study, selective colonization of gnotobiotic mice is used to demonstrate that the allergy-protective capacity is contained within the Clostridia class. Clostridia members induce IL-22 production, reducing uptake of orally administered dietary antigen into the systemic circulation and contributing to protection ... |
10.1073/pnas.0909122107 | 125,312,709 | To maintain intestinal health, the immune system must faithfully respond to antigens from pathogenic microbes while limiting reactions to self-molecules. The gastrointestinal tract represents a unique challenge to the immune system, as it is permanently colonized by a diverse amalgam of bacterial phylotypes producing m... | 10.1038/s41575-018-0064-z | Here, the immunomodulatory molecule polysaccharide A of Bacteroides fragilis is shown to mediate the conversion of CD4 + T cells into FOXP3 + regulatory T cells that produce IL-10 during commensal colonization B. fragilis co-opts the regulatory T cell lineage differentiation pathway in the gut to actively induce mucosa... |
10.1111/j.1600-065x.2006.00439.x | 38,230,981 | Summary: The eye is the prototypic immune‐privileged organ. Its antigens were once believed to be expressed exclusively in the eye, which resides behind an efficient blood–organ barrier, and were believed to be unknown to the immune system. Self‐tolerance to ocular components was therefore believed to be based not on i... | 10.1038/s41583-018-0070-8 | This paper is one of the first to argue for a re-evaluation of the benefits of CNS IP and the risks it carries as an immune defence mechanism |
10.1111/j.1750-3639.1992.tb00703.x | 38,401,046 | Cerebral extracellular fluids drain from brain to blood across the arachnoid villi and to lymph along certain cranial nerves (primarily olfactory) and spinal nerve root ganglia. Quantification of the connection to lymph in rabbit, cat and sheep, using radiolabeled albumin as a marker of flow, indicates that a minimum o... | 10.1038/s41583-018-0070-8 | This paper presents the first definitive report showing that the CNS communicates with secondary lymphoid organs — in this case, the deep cervical lymph nodes |
10.1128/cmr.00118-13 | 125,273,341 | SUMMARY The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a ... | 10.1038/s41583-018-0070-8 | This article provides a comprehensive review of the various routes through which pathogens gain access to the CNS parenchyma |
10.1126/scitranslmed.3009759 | 125,176,188 | The intestinal microbiota helps to maintain the integrity of the blood-brain barrier in fetal and adult mice. | 10.1038/s41583-018-0070-8 | This paper makes important initial observations on the effect of the microbiome on BBB function |
10.1126/science.aaz5626 | 62,328,391 | Cerebrospinal fluid (CSF) is a vital liquid, providing nutrients and signaling molecules and clearing out toxic by-products from the brain. The CSF is produced by the choroid plexus (ChP), a protective epithelial barrier that also prevents free entry of toxic molecules or drugs from the blood. Here, we establish human ... | 10.1038/s41583-021-00496-y | These authors create a choroid plexus organoid that produces cerebrospinal-like fluid and facilitates screening of drug permeation |
10.1073/pnas.1603529113 | 122,388,820 | Three-dimensional organoid constructs serve as increasingly widespread in vitro models for development and disease modeling. Current approaches to recreate morphogenetic processes in vitro rely on poorly controllable and ill-defined matrices, thereby largely overlooking the contribution of biochemical and biophysical e... | 10.1038/s41583-021-00496-y | This study uses synthetic biomaterials to systematically characterize the effects of distinct ECM-derived signalling cues on 3D neuroepithelial cysts |
10.1038/ncomms15982 | 100,529,888 | Abstract The native extracellular matrix is a space in which signals can be displayed dynamically and reversibly, positioned with nanoscale precision, and combined synergistically to control cell function. Here we describe a molecular system that can be programmed to control these three characteristics. In this approac... | 10.1038/s41583-021-00496-y | This study demonstrates a biomaterial approach to achieving temporally dynamic presentation of ECM-derived biochemical signals |
10.1073/pnas.1415330111 | 39,073,819 | Significance Human pluripotent stem (hPS) cells can self-renew indefinitely and differentiate into almost any cell type. Thus, hPS cells represent a potentially unlimited supply of cells for regenerative medicine, drug screening, and developmental studies. Realizing the full potential of hPS cells requires efficient pr... | 10.1038/s41583-021-00496-y | This study reveals that material stiffness can bias differentiation of human ES cells into a neural cell fate |
10.1002/stem.2489 | 19,671,078 | Abstract Stem cell differentiation can be highly sensitive to mechanical inputs from the extracellular matrix (ECM). Identifying temporal windows during which lineage commitment responds to ECM stiffness, and the signals that mediate these decisions, would advance both mechanistic insights and translational efforts. To... | 10.1038/s41583-021-00496-y | This study identifies a temporal window during which variations in ECM stiffness affected neural lineage commitment |
10.1073/pnas.1802568115 | 62,582,212 | Variations in a multitude of material microenvironmental properties have been observed across tissues in vivo, and these have profound effects on cell phenotype. Phenomenological experiments have suggested that certain of these features of the physical microenvironment, such as stiffness, could sensitize cells to other... | 10.1038/s41583-021-00496-y | This study reveals that culturing human NPCs in 3D biomaterials with different stress relaxation rates yields a high number of differentially expressed genes, highlighting the potential role of stress relaxation in NPC mechanosignalling |
10.1242/dev.109637 | 81,507,796 | Accumulating evidence implicates the significance of the physical properties of the niche in influencing the behavior, growth and differentiation of stem cells. Among the physical properties, extracellular stiffness has been shown to have direct effects on fate determination in several cell types in vitro. However, lit... | 10.1038/s41583-021-00496-y | The authors use atomic force microscopy to analyse the mechanical properties of the mouse embryonic cerebral cortex and find that stiffness changes over the course of development and across different subregions |
10.1126/science.aay4866 | 83,430,367 | The structural and functional complexity of multicellular biological systems, such as the brain, are beyond the reach of human design or assembly capabilities. Cells in living organisms may be recruited to construct synthetic materials or structures if treated as anatomically defined compartments for specific chemistry... | 10.1038/s41583-021-00496-y | The authors induce the polymerization of a CP on neural cell surfaces via genetic modification |
10.1038/s41467-018-05222-4 | 83,434,413 | Abstract Conductive and stretchable materials that match the elastic moduli of biological tissue (0.5–500 kPa) are desired for enhanced interfacial and mechanical stability. Compared with inorganic and dry polymeric conductors, hydrogels made with conducting polymers are promising soft electrode materials due to their ... | 10.1038/s41583-021-00496-y | The authors create mechanically tunable interpenetrating hydrogel networks with high conductivity |
10.1002/anie.199201531 | 29,322,918 | Abstract The control of crystal formation has been developed to a remarkable degree by many organisms. Oriented nucleation, control over crystal morphology, formation of unique composites of proteins and single crystals, and the production of ordered multicrystal arrays, are all well within the realm of biological capa... | 10.1038/s41585-021-00469-x | A review of the mechanisms by which organisms control the structure and mineralogy of crystallization |
10.1146/annurev-matsci-062910-095803 | 59,795,911 | A crystallization pathway describes the movement of ions from their source to the final product. Cells are intimately involved in biological crystallization pathways. In many pathways the cells utilize a unique strategy: They temporarily concentrate ions in intracellular membrane-bound vesicles in the form of a highly ... | 10.1038/s41585-021-00469-x | An evaluation of the mechanisms underlying the four most common biomineralization pathways observed in nature |
10.1002/ar.20580 | 124,133,522 | Abstract Although calcium oxalate (CaOx) renal stones are known to grow attached to renal papillae, and specifically to regions of papillae that contain Randall's plaque (interstitial apatite deposits), the mechanisms of stone overgrowth on plaque are not known. To investigate the problem, we have obtained biopsy speci... | 10.1038/s41585-021-00469-x | A detailed review of the mechanisms proposed for Randall’s plaque calcium oxalate kidney stone formation |
10.34067/kid.0006942020 | 59,512,288 | Background Human kidney stones form via repeated events of mineral precipitation, partial dissolution, and reprecipitation, which are directly analogous to similar processes in other natural and manmade environments, where resident microbiomes strongly influence biomineralization. High-resolution microscopy and high-fi... | 10.1038/s41585-021-00469-x | Provides direct evidence from both microscopy and molecular tools for entombment of a microbiome during in vivo kidney stone growth |
10.1002/jemt.22732 | 124,479,056 | Abstract The visualization of taxonomically diagnostic features of individual pollen grains can be a challenge for many ecologically and phylogenetically important pollen types. The resolution of traditional optical microscopy is limited by the diffraction of light (250 nm), while high resolution tools such as electron... | 10.1038/s41585-021-00469-x | A detailed description of the super-resolution autofluorescence (SRAF) technique, which has been applied to characterize kidney stone paragenetic sequences and diagenetic phase transitions |
10.1038/s41598-018-30717-x | 60,972,394 | Abstract Nephrocalcinosis often begins on a calcium phosphate deposit, at the tip of the medullo-papillary complex (MPC) known as Randall’s plaque (RP). Contextualizing proximally observed biominerals within the MPC has led us to postulate a mechanobiological switch that can trigger interstitial biomineralization at th... | 10.1038/s41585-021-00469-x | A description and proposed interpretation of the continuum of biomineralization events within the renal pyramid as detected with high-resolution micro-computed tomography (micro-CT) |
10.1111/j.1365-3091.2010.01209.x | 45,346,683 | Abstract Multiple abiotic and biotic factors combine in nature to influence the formation of calcium carbonate limestone deposits. Systems Geobiology studies of how micro‐organisms respond to, or sometimes even control, the coupled effects of environmental change and mineralization will permit more accurate interpretat... | 10.1038/s41585-021-00469-x | A comprehensive review of the physical, chemical and biological factors and mechanisms that control biomineralization in hot springs |
10.1002/chem.201601280 | 82,147,850 | Abstract Crystallization from amorphous phases is an emerging pathway for making advanced materials. Biology has made use of amorphous precursor phases for eons and used them to produce structures with remarkable properties. Herein, we show how the design of the amorphous phase greatly influences the nanocrystals forme... | 10.1038/s41585-021-00469-x | This study experimentally demonstrates the mineralization pathway from amorphous calcium phosphate and mixed amorphous calcium carbonate to apatite kidney stone formation |
10.1177/10454411920030010601 | 102,722,436 | Studies of apatite mineral formation are complicated by the possibility of forming several calcium phosphate phases. The least soluble, hydroxyapatite (HAP), is preferentially formed under neutral or basic conditions. In more acidic solutions phases such as dicalcium phosphate dihydrate (Brushite, DCPD) and octacalcium... | 10.1038/s41585-021-00469-x | A detailed theoretical and experimental summary of the diagenetic phase transitions is presented, from the unstable polymorphs of calcium phosphate to tricalcium phosphate and octacalcium phosphate |
10.1039/c9ce01587f | 121,740,319 | The development of a flow-cell platform is reported that utilizes basement membrane extract as a biologically relevant crystallization substrate to study the effect of urinary inhibitors on the in situ formation of calcium oxalate/phosphate. | 10.1038/s41585-021-00469-x | A microfluidic in vitro study of calcium phosphate and calcium oxalate crystal formation on the basement membrane and the impact of crystallization inhibitors |
10.1158/0008-5472.can-11-1154 | 20,033,559 | Abstract Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which ex... | 10.1038/s41585-019-0185-3 | This comparison of two different MS modalities measuring the same sample set reveals different metabolomic patterns |
10.1038/srep19763 | 20,376,915 | Abstract Hepatocarcinoma (HCC) is one of the deadliest cancers in the world and represents a significant disease burden. Better biomarkers are needed for early detection of HCC. Metabolomics was applied to urine samples obtained from HCC patients to discover noninvasive and reliable biomarkers for rapid diagnosis of HC... | 10.1038/s41585-019-0185-3 | This article shows the great potential of urinary metabolomics for cancer detection at an early stage and contains a thorough pathway analysis |
10.1002/jcsm.12246 | 60,986,018 | Abstract Background Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the ... | 10.1038/s41585-019-0185-3 | This paper shows that metabolomic biomarker panels can be useful not just for identifying cancer but also for identifying the condition of cachexia, which is associated with malignancies |
10.1101/2020.03.23.003749 | 100,192,704 | Abstract The alarmones pppGpp and ppGpp (collectively (p)ppGpp) protect bacterial cells from nutritional and other stresses. Here we demonstrate the physiological presence of pGpp as a third closely related alarmone in bacterial cells and also characterize and compare the proteomic targets of pGpp, ppGpp and pppGpp in ... | 10.1038/s41579-020-00470-y | The authors show the production of pGpp in vivo via the hydrolysis of (p)ppGpp |
10.1073/pnas.1505271112 | 41,134,604 | Nucleotide-based second messengers serve in the response of living organisms to environmental changes. In bacteria and plant chloroplasts, guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) [collectively named “(p)ppGpp”] act as alarmones that globally reprogram cellular physiology during various st... | 10.1038/s41579-020-00470-y | This article is the first to show allosteric regulation of an SAS, which had been previously overlooked due to the absence of a C-terminal regulatory region |
10.7554/elife.17029 | 81,549,652 | Stringent response is a conserved bacterial stress response underlying virulence and antibiotic resistance. RelA/SpoT-homolog proteins synthesize transcriptional modulators (p)ppGpp, allowing bacteria to adapt to stress. RelA is activated during amino-acid starvation, when cognate deacyl-tRNA binds to the ribosomal A (... | 10.1038/s41579-020-00470-y | This is one of three articles showing the structure of RelA in complex with the 70S ribosome |
10.1128/jb.00258-12 | 85,673,382 | ABSTRACT In the noninfectious soil saprophyte Mycobacterium smegmatis , intracellular levels of the stress alarmones guanosine tetraphosphate and guanosine pentaphosphate, together termed (p)ppGpp, are regulated by the enzyme Rel Msm . This enzyme consists of a single, bifunctional polypeptide chain that is capable of ... | 10.1038/s41579-020-00470-y | This article identifies the first RSH superfamily enzyme that has an enzymatic domain that is not involved in (p)ppGpp metabolism |
10.1073/pnas.1720406115 | 17,362,691 | Riboswitches are noncoding portions of certain mRNAs that bind metabolite, coenzyme, signaling molecule, or inorganic ion ligands and regulate gene expression. Most known riboswitches sense derivatives of RNA monomers. This bias in ligand chemical composition is consistent with the hypothesis that widespread riboswitch... | 10.1038/s41579-020-00470-y | This article is the first to show ppGpp binding of non-protein targets and suggests an evolutionary link between the stringent response and the RNA world |
10.1128/jb.01195-08 | 80,475,625 | ABSTRACT Bacteria respond to nutritional stress by producing (p)ppGpp, which triggers a stringent response resulting in growth arrest and expression of resistance genes. In Escherichia coli , RelA produces (p)ppGpp upon amino acid starvation by detecting stalled ribosomes. The SpoT enzyme responds to various other type... | 10.1038/s41579-020-00470-y | This article shows that SpoT mediates a response to fatty acid starvation through interaction with ACP |
10.1128/mmbr.00046-09 | 28,266,416 | SUMMARY Like for all microbes, the goal of every pathogen is to survive and replicate. However, to overcome the formidable defenses of their hosts, pathogens are also endowed with traits commonly associated with virulence, such as surface attachment, cell or tissue invasion, and transmission. Numerous pathogens couple ... | 10.1038/s41579-020-00470-y | This is an extensive review on the impact of the stringent response on pathogenicity in several bacterial species |
10.1002/mrm.21404 | 124,843,779 | Abstract The purpose of this analysis is to explore the potential diagnostic gain provided by the viscoelastic shear properties of breast lesions for the improvement of the specificity of contrast enhanced dynamic MR mammography (MRM). The assessment of viscoelastic properties is done via dynamic MR elastography (MRE) ... | 10.1038/s41586-020-2612-2 | These studies (Streitberger et al. (2014) and Sinkus et al. (2007)) utilized magnetic resonance elastography to analyse changes in tissue viscoelasticity during cancer, and find that there were striking differences in viscoelasticity between malignant and benign breast tumors, and between glioblastoma and healthy brain... |
10.1115/1.4038745 | 71,878,971 | Rotator cuff disorders are one of the most common causes of shoulder pain and disability in the aging population but, unfortunately, the etiology is still unknown. One factor thought to contribute to the progression of disease is the external compression of the rotator cuff tendons, which can be significantly increased... | 10.1038/s41586-020-2612-2 | This and earlier related studies emphasize the importance of poroelastic relaxation in the design of tissues and their changes with injury, disease and ageing |
10.1038/s41467-018-02906-9 | 20,462,633 | Abstract The mechanical properties of extracellular matrices can control the function of cells. Studies of cellular responses to biomimetic soft materials have been largely restricted to hydrogels and elastomers that have stiffness values independent of time and extent of deformation, so the substrate stiffness can be ... | 10.1038/s41586-020-2612-2 | This study reported a method of producing viscoelastic solid substrates with separately tunable elastic and viscous moduli and showed that several cell types respond to viscoelastic substrates as though they were softer than purely elastic substrates of the same elastic modulus |
10.1073/pnas.1716620115 | 20,462,647 | Recent evidence has shown that, in addition to rigidity, the viscous response of the extracellular matrix (ECM) significantly affects the behavior and function of cells. However, the mechanism behind such mechanosensitivity toward viscoelasticity remains unclear. In this study, we systematically examined the dynamics o... | 10.1038/s41586-020-2612-2 | This study used analytical and Monte Carlo methods to simulate the dynamics of motor clutches (focal adhesions) formed between the cell and a viscoelastic substrate, and found that that intermediate viscosity maximizes cell spreading on soft substrates, while cell spreading is independent of viscosity on stiff substrat... |
10.1073/pnas.1802568115 | 62,582,212 | Variations in a multitude of material microenvironmental properties have been observed across tissues in vivo, and these have profound effects on cell phenotype. Phenomenological experiments have suggested that certain of these features of the physical microenvironment, such as stiffness, could sensitize cells to other... | 10.1038/s41586-020-2612-2 | This work revealed that the transcriptional responses of cells in three-dimensional culture to stress relaxation, matrix stiffness and adhesion ligand density exhibit substantial independent effects and coupling among these properties, demonstrating a clear cell type and context dependence of viscoelasticity sensing |
10.1038/s41467-018-06641-z | 83,188,828 | Abstract Studies of cancer cell migration have found two modes: one that is protease-independent, requiring micron-sized pores or channels for cells to squeeze through, and one that is protease-dependent, relevant for confining nanoporous matrices such as basement membranes (BMs). However, many extracellular matrices e... | 10.1038/s41586-020-2612-2 | This study demonstrated that mechanical plasticity in nanoporous matrices allows protease-independent migration of cancer cells, with cells using invadopodial protrusions to mechanically open up micrometre-size channels to migrate through |
10.1073/pnas.1511304112 | 27,890,566 | Biomaterials that mimic aspects of the extracellular matrix by presenting a 3D microenvironment that cells can locally degrade and remodel are finding increased applications as wound-healing matrices, tissue engineering scaffolds, and even substrates for stem cell expansion. In vivo, cells do not simply reside in a sta... | 10.1038/s41586-020-2612-2 | This study examined how the viscoelastic properties of PEG hydrogels with degradable crosslinks were altered due to cellular degradation during migration of mesenchymal stem cells and found that the cells converted the elastic hydrogel into a viscoelastic fluid |
10.1038/s41467-019-08465-x | 83,366,760 | Abstract For mesenchymal stem cells (MSCs) cultured in three dimensional matrices, matrix remodeling is associated with enhanced osteogenic differentiation. However, the mechanism linking matrix remodeling in 3D to osteogenesis of MSCs remains unclear. Here, we find that MSCs in viscoelastic hydrogels exhibit volume ex... | 10.1038/s41586-020-2612-2 | This study identified the role of cell volume expansion and activation of mechanosensitive ion channels in mediating how mesenchymal stem cells sense matrix viscoelasticity |
10.1126/science.1093889 | 79,371,359 | Forkhead transcription factors play key roles in the regulation of immune responses. Here, we identify a role for one member of this family, Foxj1, in the regulation of T cell activation and autoreactivity. Foxj1 deficiency resulted in multiorgan systemic inflammation, exaggerated Th1 cytokine production, and T cell pr... | 10.1038/s41577-018-0048-9 | This paper demonstrates a role for FOXJ1 in T cell homeostasis |
10.1084/jem.20161263 | 102,499,744 | Germinal center (GC) B cells cycle between two states, the light zone (LZ) and the dark zone (DZ), and in the latter they proliferate and hypermutate their immunoglobulin genes. How this functional transition takes place is still controversial. In this study, we demonstrate that ablation of Foxo1 after GC development l... | 10.1038/s41577-018-0048-9 | References 68–70 reveal that FOXO1 is involved in the regulation of B cell GC reactions |
10.1038/s41419-020-2290-x | 60,682,928 | Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disease with a strong heritability, but recent evidence suggests that epigenetic dysregulation may also contribute to the pathogenesis of ASD. Especially, increased methylation at the MECP2 promoter and decreased MECP2 expression were observed in the brain... | 10.1038/s41583-020-0334-y | DNA methylation of the Mecp2 promoter in the hippocampus is achieved by targeting dCas9 fused to a DNMT catalytic domain to the locus. This action suppresses Mecp2 expression and is sufficient to induce autism-like behavioural phenotypes |
10.1038/ncomms15993 | 62,128,883 | Abstract Chromatin looping is key to gene regulation, yet no broadly applicable methods to selectively modify chromatin loops have been described. We have engineered a method for chromatin loop reorganization using CRISPR-dCas9 (CLOuD9) to selectively and reversibly establish chromatin loops. We demonstrate the power o... | 10.1038/s41583-020-0334-y | CRISPR tools are used to chemically induce, in a reversible manner, the chromatin looping between two genes |
10.1098/rstb.2014.0224 | 41,543,237 | Evolutionary considerations suggest that oncogenic infections should be pervasive among animal species. Infection-associated cancers are well documented in humans and domestic animals, less commonly reported in undomesticated captive animals, and rarely documented in nature. In this paper, we review the literature asso... | 10.1038/s41568-018-0045-0 | This paper reviews the diversity of known pathogen-derived neoplasms among all types of multicellular organisms and also addresses the challenges in recognizing cancer in nature |
10.1126/science.1152586 | 125,299,557 | Merkel cell carcinoma (MCC) is a rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin. We studied MCC samples by digital transcriptome subtraction and detected a fusion transcript between a previously undescribed virus T anti... | 10.1038/s41568-018-0045-0 | This paper uses a focused subtractive viral discovery scheme to find an integrated causative virus in the case of Merkel cell carcinoma of humans. The basis for the search was an association of the cancer with immunosuppression, which underscores the importance of host immunity in the case of viral-associated oncogenes... |
10.1128/mbio.02079-16 | 17,621,993 | ABSTRACT Merkel cell polyomavirus is the primary etiological agent of the aggressive skin cancer Merkel cell carcinoma (MCC). Recent studies have revealed that UV radiation is the primary mechanism for somatic mutagenesis in nonviral forms of MCC. Here, we analyze the whole transcriptomes and genomes of primary MCC tum... | 10.1038/s41568-018-0045-0 | This paper shows how oncogenic proteins of viruses, in this case the T Ag of PyVs, are powerful substitutes for the numerous genetic mutations that usually precede transformation in non-virus-associated cancers |
10.1128/jvi.01912-14 | 59,108,165 | ABSTRACT Raccoon polyomavirus (RacPyV) is associated with 100% of neuroglial tumors in free-ranging raccoons. Other tumor-associated polyomaviruses (PyVs), including simian virus 40 (SV40), murine PyV, and Merkel cell PyV, are found integrated in the host genome in neoplastic cells, where they constitutively express sp... | 10.1038/s41568-018-0045-0 | The data presented in this paper fulfil some of the criteria for viral causality in a wildlife cancer. The stability of the virus as an episome is considered a different oncogenic mechanism than that of the other known PyV associated with cancer (MCPyV) |
10.1098/rstb.2014.0228 | 84,497,581 | Naturally occurring cancers in non-laboratory species have great potential in helping to decipher the often complex causes of neoplasia. Wild animal models could add substantially to our understanding of carcinogenesis, particularly of genetic and environmental interactions, but they are currently underutilized. Studyi... | 10.1038/s41568-018-0045-0 | This study highlights how urogenital carcinomas in the California sea lion provide a remarkable model of the complex interaction of environment, pathogens and genetics that are likely involved in most wildlife cancers and that are among the most studied |
10.1146/annurev-virology-100114-055056 | 102,098,179 | A retroviral etiology for malignant neoplasias in koalas has long been suspected. Evidence for retroviral involvement was bolstered in 2000 by the isolation of a koala retrovirus (KoRV), now termed KoRV-A. KoRV-A is an endogenous retrovirus—a retrovirus that infects germ cells—a feature that makes it a permanent reside... | 10.1038/s41568-018-0045-0 | This paper reveals how koala retroviruses are likely in a unique transient state, as they are presently evolving into endogenous retroviruses, providing an opportunity to study this phenomenon |
10.1177/0300985815604726 | 104,327,220 | An isolated population of beluga ( Delphinapterus leucas) inhabits the St Lawrence Estuary, Quebec, Canada. This population has failed to recover despite the prohibition of hunting >30 years ago, suggesting the presence of other limiting factors. The authors summarize the reported causes of death and propose risk fa... | 10.1038/s41568-018-0045-0 | This study is important, given the multifactorial effects of toxins on cancer formation and reproductive health, as it identifies both malignant tumours and reproductive diseases as contributing to the declining numbers of beluga in this region, a species that, despite efforts of protection, has not recovered over the ... |
10.1158/2159-8290.cd-19-0442 | 101,113,783 | Abstract The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overex... | 10.1038/s41568-021-00412-7 | This study describes a large-scale umbrella trial for GC, allocating patients based on genomic biomarkers |
10.1093/pcmedi/pby007 | 67,418,856 | Abstract Cancer is a heterogeneous disease with unique genomic and phenotypic features that differ between individual patients and even among individual tumor regions. In recent years, large-scale genomic studies and new next-generation sequencing technologies have uncovered more scientific details about tumor heteroge... | 10.1038/s41568-021-00412-7 | Together with Janjigian et al (2018), this study describes inter-patient and intra-patient heterogeneity as a barrier to treatment responses and liquid biopsies as a potential strategy to circumvent this barrier |
10.1038/s41467-018-03828-2 | 62,194,882 | Abstract Tissue-specific driver mutations in non-coding genomic regions remain undefined for most cancer types. Here, we unbiasedly analyze 212 gastric cancer (GC) whole genomes to identify recurrently mutated non-coding regions in GC. Applying comprehensive statistical approaches to accurately model background mutatio... | 10.1038/s41568-021-00412-7 | This study describes frequent non-coding mutations at CTCF-binding sites in GC |
10.1038/ncomms12983 | 61,893,512 | Abstract Regulatory enhancer elements in solid tumours remain poorly characterized. Here we apply micro-scale chromatin profiling to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating 110 epigenomic profiles from primary GCs, normal gastr... | 10.1038/s41568-021-00412-7 | This study describes a genome-wide survey of altered enhancer and super-enhancer elements in GC |
10.1158/2159-8290.cd-16-1022 | 109,425,892 | Abstract Promoter elements play important roles in isoform and cell type–specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma, analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary gastric cancers, gastric cancer lines, and nonmalignant gastric tissues. We ident... | 10.1038/s41568-021-00412-7 | This study describes frequent usage of alternate promoters in GC and their contribution to immune evasion |
10.1136/gutjnl-2018-318070 | 122,460,208 | Objective Peritoneal carcinomatosis (PC) occurs frequently in patients with gastric adenocarcinoma (GAC) and confers a poor prognosis. Multiplex profiling of primary GACs has been insightful but the underpinnings of PC’s development/progression remain largely unknown. We characterised exome/transcriptome/immune landsca... | 10.1038/s41568-021-00412-7 | This study reports differences in the molecular profiles of primary GCs and peritoneal metastases |
10.1136/gutjnl-2020-322065 | 125,038,582 | Objective An unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with all stages of gastric cancer from a high-risk population. Design We conducted a three-phase, multicentre study comprising 5248 subjects from... | 10.1038/s41568-021-00412-7 | This study describes an miRNA blood panel for early GC detection in high-risk populations |
10.1073/pnas.1906958116 | 20,806,614 | Bacteria evolve by mutation accumulation in laboratory experiments, but tempo and mode of evolution in natural environments are largely unknown. Here, we study the ubiquitous natural process of host colonization by commensal bacteria. We show, by experimental evolution of Escherichia coli in the mouse intestine, that t... | 10.1038/s41579-021-00650-4 | Using the mouse microbiome as a study system, the authors show that rapid, phage-mediated HGT can transfer beneficial genes — already present in a resident strain — to an invading strain |
10.1073/pnas.1405336111 | 123,120,106 | Significance Several molecular systems with important adaptive roles have originated from the domestication of integrated phages (prophages). However, the evolutionary mechanisms and extent of prophage domestication remain poorly understood. In this work, we detected several hundred prophages originating from common in... | 10.1038/s41579-021-00650-4 | Although prophages can be considered parasitic, the authors show evidence of purifying selection within prophage genes, suggesting that they serve a beneficial purpose within their bacterial hosts |
10.21203/rs.3.rs-89984/v2 | 118,970,483 | Abstract The authors have requested that this preprint be withdrawn due to author disagreement. | 10.1038/s41585-018-0020-2 | This paper describes the intracardiac injection method of cancer cell inoculation, first described by Haq et al., that is a cornerstone method to produce bone metastases. |
10.1159/000131743 | 47,068,758 | Three SV40-transformed derivatives (Tl, T2, and T5) of human prostatic epithelial cells were analyzed karyotypically. For comparison, an SV40 derivative (TA) obtained from isogenic fibroblasts, was also studied. The chromosome complements of these cells, as well as a subclone of T2 isolated in soft agar (T2-A5), were a... | 10.1038/s41585-018-0020-2 | In this article, Kaighn et al. describe the predominant cell line in prostate cancer research, PC3. |
10.1126/science.1256478 | 41,657,302 | Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. We report that neutrophil polarization within activated venules served to organize a protr... | 10.1038/s41577-019-0202-z | The authors demonstrate that neutrophils scan the inflamed vasculature for activated platelets and show that the neutrophils’ bipolarity allows the integration of signals from the endothelium and the circulation |
10.1158/0008-5472.can-09-1370 | 47,619,003 | Abstract Solid tumors generate a prothrombotic environment capable of platelet activation. Recent findings indicate that the activated platelets are crucial regulators of tumor vascular homeostasis in that they prevent tumor hemorrhage. Surprisingly, this effect is independent of platelets' capacity to form thrombi and... | 10.1038/s41577-019-0202-z | The authors provide a comprehensive review of activated platelets as crucial regulators of tumour vascular homeostasis preventing tumour haemorrhage |
10.1182/blood-2007-09-113837 | 83,445,811 | Abstract Platelets, in addition to their function in hemostasis, play an important role in wound healing and tumor growth. Because platelets contain angiogenesis stimulators and inhibitors, the mechanisms by which platelets regulate angiogenesis remain unclear. As platelets adhere to activated endothelium, their action... | 10.1038/s41577-019-0202-z | The authors demonstrate that separate packaging of angiogenesis regulators into pharmacologically and morphologically distinct populations of α-granules in megakaryocytes and platelets provides a mechanism by which platelets can locally stimulate or inhibit angiogenesis |
10.1182/blood-2008-06-159541 | 104,262,454 | Abstract Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of ... | 10.1038/s41577-019-0202-z | This study identifies the ability of platelets to selectively take up angiogenesis regulators in cancer-bearing hosts |
10.1182/blood-2016-11-751099 | 41,702,281 | Key Points Platelet MPs infiltrate solid tumors and transfer platelet-derived miRNAs to tumor cells within solid tumors in vivo. Transfer of platelet miRNAs to tumor cells results in downregulation of tumor cell genes and inhibition of solid tumor growth. | 10.1038/s41577-019-0202-z | The authors show platelet-derived microparticles may shuttle platelet-derived microRNA to tumour cells in solid tumours, regulating tumour cell gene expression and modulating tumour progression |
10.1038/s41467-017-00201-7 | 124,827,722 | Abstract In mammals, megakaryocytes (MKs) in the bone marrow (BM) produce blood platelets, required for hemostasis and thrombosis. MKs originate from hematopoietic stem cells and are thought to migrate from an endosteal niche towards the vascular sinusoids during their maturation. Through imaging of MKs in the intact B... | 10.1038/s41577-019-0202-z | The authors provide evidence that megakaryocytes are largely sessile cells in close contact with the vasculature and homogeneously distributed in the bone marrow |
10.1038/s41467-017-00411-z | 82,905,312 | Abstract Thrombocytosis is present in more than 30% of patients with solid malignancies and correlates with worsened patient survival. Tumor cell interaction with various cellular components of the tumor microenvironment including platelets is crucial for tumor growth and metastasis. Although it is known that platelets... | 10.1038/s41577-019-0202-z | This study shows that platelets increase cancer metastasis by activating YAP1 through a RhoA signalling pathway |
10.1073/pnas.1719115115 | 123,202,093 | Proteins fold to their lowest free-energy structures, and hence the most straightforward way to increase the accuracy of a partially incorrect protein structure model is to search for the lowest-energy nearby structure. This direct approach has met with little success for two reasons: first, energy function inaccuracie... | 10.1038/s41580-019-0163-x | Heo et al. and Park et al. report substantial progress in refinement of protein structure models by physics-based simulations. |
10.1126/science.aav7541 | 103,726,720 | The features that stabilize the structures of membrane proteins remain poorly understood. Polar interactions contribute modestly, and the hydrophobic effect contributes little to the energetics of apolar side-chain packing in membranes. Disruption of steric packing can destabilize the native folds of membrane proteins,... | 10.1038/s41580-019-0163-x | This study reports on the design of helical membrane proteins with only apolar interactions between side chains, which demonstrates that hydrogen bonding between helices is not required for the folding and stability of membrane proteins. |
10.1126/science.aah4043 | 103,743,893 | Filling in the protein fold picture Fewer than a third of the 14,849 known protein families have at least one member with an experimentally determined structure. This leaves more than 5000 protein families with no structural information. Protein modeling using residue-residue contacts inferred from evolutionary data ha... | 10.1038/s41580-019-0163-x | This study shows that inclusion of sequence data from metagenomics triples the number of protein families for which accurate structural models can be built using folding simulations that incorporate covariation-derived residue–residue contact predictions. |
10.1126/science.aaf8818 | 83,178,010 | Designed to assemble Symmetric macromolecular structures that form cages, such as viral capsids, have inspired protein engineering. Bale et al. used pairwise combinations of dimeric, trimeric, or pentameric building blocks to design two-component, 120-subunit protein complexes with three distinct icosahedral architectu... | 10.1038/s41580-019-0163-x | One of several papers in which this team demonstrate that protein interface design combined with modelling of higher-order symmetries can be used to create large, multi-component protein cages. |
10.1136/jmedgenet-2019-106084 | 83,096,523 | Primary lymphatic anomalies may present in a myriad of ways and are highly heterogenous. Careful consideration of the presentation can lead to an accurate clinical and/or molecular diagnosis which will assist with management. The most common presentation is lymphoedema, swelling resulting from failure of the peripheral... | 10.1038/s41572-021-00309-7 | This review proposes an updated clinical classification algorithm for primary lymphoedema to assist diagnostic workup and patient management, based on age of onset, areas affected by swelling and associated clinical features, in agreement with the International Society for the Study of Vascular Anomalies 2018 classific... |
10.1126/scitranslmed.aax8013 | 82,624,456 | Primary lymphedema is caused by developmental and functional defects of the lymphatic vascular system that result in accumulation of protein-rich fluid in tissues, resulting in edema. The 28 currently known genes causing primary lymphedema can explain <30% of cases. Angiopoietin 1 (ANGPT1) and ANGPT2 function via th... | 10.1038/s41572-021-00309-7 | This is the most recent discovery of a novel gene causing primary lymphoedema with functional validation of the mutations in vitro and in a mouse model, underscoring the heterogeneity within genetic causes of PLE |
10.2458/lymph.4649 | 133,496,725 | THE DIAGNOSIS AND TREATMENT OF PERIPHERAL LYMPHEDEMA: 2020 CONSENSUS DOCUMENT OF THE INTERNATIONAL SOCIETY OF LYMPHOLOGY | 10.1038/s41572-021-00309-7 | This recent document integrates the broad spectrum of protocols and practices advocated around the world for the diagnosis and treatment of peripheral lymphoedema. It provides a current “Consensus view” of the international community based on various levels of evidence. |
10.1161/circresaha.121.318145 | 128,120,792 | Vascular and lymphatic malformations represent a challenge for clinicians. The identification of inherited and somatic mutations in important signaling pathways, including the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin), RAS (rat sarcoma)/RAF (rapidly accelerated fibrosa... | 10.1038/s41572-021-00309-7 | This recent review describes the genetic and pathophysiological discoveries in the field of vascular anomalies and the current status of repurposing of cancer drugs for their targeted management (theranostics). |
10.1161/circresaha.121.318142 | 128,121,234 | Lymphatic vessels maintain tissue fluid homeostasis by returning to blood circulation interstitial fluid that has extravasated from the blood capillaries. They provide a trafficking route for cells of the immune system, thus critically contributing to immune surveillance. Developmental or functional defects in the lymp... | 10.1038/s41572-021-00309-7 | This recent review portrays the numerous discoveries made on the genetic and pathophysiological bases of lymphatic malformations and understanding of the molecular and cellular mechanisms involved. It also illustrates the fast progress made in the repurposing of small molecule inhibitors developed for oncology for the ... |
10.1002/alr.22070 | 83,032,554 | Background The available allergic rhinitis (AR) literature continues to grow. Critical evaluation and understanding of this literature is important to appropriately utilize this knowledge in the care of AR patients. The International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR) has been pro... | 10.1038/s41572-020-00227-0 | In this critical review of the AR literature, the authors apply a systematic evidence-based approach to provide a comprehensive, clinical update on current knowledge of AR and to identify knowledge gaps for future studies |
10.1111/all.14314 | 19,084,857 | Abstract Background Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large‐scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes. Methods Integrated trans... | 10.1038/s41572-020-00227-0 | This MeDALL collaborative study represents the largest transcriptomics allergy dataset published to date and describes unique blood gene expression signatures in allergic multimorbidity versus rhinitis only |
10.1111/imr.12555 | 20,396,578 | Summary Allergy is a major public health problem with a high socio‐economic impact. The number of allergic patients is expected to reach to four billion within two decades when the World's population reaches to 10 billion. Our knowledge on the molecular mechanisms underlying allergic diseases and allergen tolerance ind... | 10.1038/s41572-020-00227-0 | This is a comprehensive review discussing the role of regulatory T and B cells in the induction and maintenance of tolerance in allergic diseases, including AR. A deeper analysis of the molecular mechanism governing the generation of regulatory T cells and B cells in tolerance and discussion of how this could be exploi... |
10.1111/cea.12780 | 103,082,121 | Summary Rhinitis is a heterogeneous condition that has been associated with inflammatory responses as in allergic rhinitis but can also occur in the absence of inflammation such as in so‐called idiopathic (previously ‘vasomotor’) rhinitis. Allergic rhinitis affects approximately one in four of the population of western... | 10.1038/s41572-020-00227-0 | This review illustrates key concepts of the pathogenesis of different forms of rhinitis. Environmental factors in association with imbalance in innate and adaptive immunity factors are likely to play major roles. Evidence for nasal priming and remodelling in AR are reviewed. Local AR in the absence of systemic IgE is d... |
10.1186/2045-7022-1-2 | 20,360,038 | Abstract This EAACI Task Force document aims at providing the readers with a comprehensive and complete overview of the currently available tools for diagnosis of nasal and sino‐nasal disease. We have tried to logically order the different important issues related to history taking, clinical examination and additional ... | 10.1038/s41572-020-00227-0 | A panel of European experts in the field of rhinology contributed to this consensus document on diagnostic tools in rhinology. This EAACI Task Force document aims at providing readers with a comprehensive and complete overview of currently available tools for diagnosis of nasal and sinonasal disease. The different impo... |
10.1038/s41558-022-01282-z | 128,026,808 | Abstract Sea surface temperature (SST) variability of El Niño–Southern Oscillation (ENSO) underpins its global impact, and its future change is a long-standing science issue. In its sixth assessment, the IPCC reports no systematic change in ENSO SST variability under any emission scenarios considered. However, comparis... | 10.1038/s41558-022-01406-5 | This paper reports a strong inter-model consensus on the projected increase of ENSO variability from the twentieth century to the twenty-first century under all plausible emission scenarios |
10.1038/s41467-021-22900-y | 2,445,517 | Abstract CRISPR-Cas systems provide adaptive immunity in bacteria and archaea, beginning with integration of foreign sequences into the host CRISPR genomic locus and followed by transcription and maturation of CRISPR RNAs (crRNAs). In some CRISPR systems, a reverse transcriptase (RT) fusion to the Cas1 integrase and Ca... | 10.1038/s41579-022-00739-4 | This work describes the structure of a Cas6–RT–Cas1–Cas2 complex, highlighting interactions between the three domains and the potential functional implications for CRISPR adaptation |
10.1038/s41586-022-04470-1 | 136,151,131 | Abstract CRISPR–Cas9 as a programmable genome editing tool is hindered by off-target DNA cleavage 1–4 , and the underlying mechanisms by which Cas9 recognizes mismatches are poorly understood 5–7 . Although Cas9 variants with greater discrimination against mismatches have been designed 8–10 , these suffer from substant... | 10.1038/s41579-022-00739-4 | This study demonstrates how excessive target mismatches inhibit DNA cutting by Cas9 and reveals a most comprehensive structure of Cas9 bound to the DNA cleavage product |
10.1126/science.abi8976 | 132,528,639 | Target site selection in CAST systems Exciting genomic engineering possibilities exist for natural integration systems called transposons, which have co-opted CRISPR/Cas systems. An unexplained feature of these systems involves how they direct insertions in a single orientation at a precise distance from the programmed... | 10.1038/s41579-022-00739-4 | This work provides mechanistic insights into subtype V-K CRISPR transposases by describing a transposition regulator, TnsC, from a subtype V-K CAST system and its interaction with TniQ and proposing a model for subtype V-K CAST transposition |
10.1542/peds.2007-1105 | 124,535,681 | OBJECTIVE. The purpose of this work was to determine the prevalence and predictors of diabetic ketoacidosis at the diagnosis of diabetes in a large sample of youth from the US population. PATIENTS AND METHODS. The Search for Diabetes in Youth Study, a multicenter, population-based registry of diabetes with diagnosis be... | 10.1038/s41572-020-0165-1 | This large dataset shows that, in the USA, 1 in 4 people <20 years of age presented with DKA at the time of diagnosis of diabetes mellitus |
10.1111/dme.12875 | 18,222,681 | Abstract Aim To examine, in a national survey, the outcomes of adult patients presenting with DKA in 2014, mapped against accepted UK national guidance. Methods Data were collected in a standardized form covering clinical and biochemical outcomes, risk and discharge planning. The form was sent to all UK diabetes specia... | 10.1038/s41572-020-0165-1 | This paper shows that the UK guideline works and that hypoglycaemia and hypokalaemia are common |
10.2337/dc15-0780 | 105,383,288 | OBJECTIVE Diabetic ketoacidosis (DKA) in children and adolescents with established type 1 diabetes is a major problem with considerable morbidity, mortality, and associated costs to patients, families, and health care systems. We analyzed data from three multinational type 1 diabetes registries/audits with similarly ad... | 10.1038/s41572-020-0165-1 | This very large dataset looks at the risk factors for developing DKA in children <18 years of age with established T1DM |
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