source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1182/blood-2012-01-405365 | 60,130,712 | Abstract Clinical-grade T cells are genetically modified ex vivo to express a chimeric antigen receptor (CAR) to redirect specificity to a tumor associated antigen (TAA) thereby conferring antitumor activity in vivo. T cells expressing a CD19-specific CAR recognize B-cell malignancies in multiple recipients independent... | 10.1038/s41573-019-0051-2 | This is a seminal study describing the development of allogeneic universal CAR T cells based on the elimination of the TCR by gene editing. |
10.1126/scitranslmed.aaj2013 | 45,559,873 | Universal gene-edited CAR19 T cells eliminate infant leukemia. | 10.1038/s41573-019-0051-2 | This article reports the first clinical results obtained with allogeneic gene-edited CAR T cells. |
10.1126/science.1076514 | 62,136,737 | We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cance... | 10.1038/s41573-019-0051-2 | This seminal study shows that a lymphodepleting chemotherapy allows efficient expansion of the administered T cells in patients, which is associated with clinical efficacy. |
10.5966/sctm.2015-0049 | 83,117,814 | Abstract Human embryonic stem cells (hESCs) are a promising source of cells for tissue regeneration, yet histoincompatibility remains a major challenge to their clinical application. Because the human leukocyte antigen class I (HLA-I) molecules are the primary mediators of immune rejection, we hypothesized that cells d... | 10.1038/s41573-019-0051-2 | Demonstration of the elimination of MHC class I molecule expression by disruption of the gene encoding β 2 -microglobulin. |
10.1098/rsta.1920.0009 | 38,396,502 | 1. The purpose of the expeditions was to determine what effect, if any, is produced by a gravitational field on the path of a ray of light traversing it. Apart from possible surprises, there appeared to be three alternatives, which it was especially desired to discriminate between— (1) The path is uninfluenced by gravi... | 10.1038/s41586-019-1129-z | This paper reported that observations of the 1919 solar eclipse confirmed Einstein’s prediction of gravitational light deflection. |
10.3847/1538-4357/aae9de | 104,137,474 | Abstract The multiwavelength nonthermal emission from the binary neutron star merger event GW170817/GRB170817A has raised a heated debate concerning the post-merger outflow structure. Both a relativistic structured jet viewed off-axis and a mildly relativistic quasi-spherical outflow can explain the observational data ... | 10.1038/s41586-019-1129-z | First detection of gravitational waves from a double neutron star binary. |
10.1038/s41586-020-1969-6 | 20,697,450 | Abstract Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale 1–3 . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-... | 10.1038/s41587-022-01552-3 | This consortium study reports the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumor types. |
10.1073/pnas.1809700115 | 82,861,331 | Lower respiratory tract infections (LRTIs) lead to more deaths each year than any other infectious disease category. Despite this, etiologic LRTI pathogens are infrequently identified due to limitations of existing microbiologic tests. In critically ill patients, noninfectious inflammatory syndromes resembling LRTIs fu... | 10.1038/s41576-019-0113-7 | This study integrates microbial metagenomic and host response NGS data to improve accuracy in diagnosing lower respiratory tract infections |
10.1101/330381 | 74,037,201 | ABSTRACT Metagenomic next-generation sequencing (mNGS) for pan-pathogen detection has been successfully tested in proof-of-concept case studies in patients with acute illness of unknown etiology, but to date has been largely confined to research settings. Here we developed and validated an mNGS assay for diagnosis of i... | 10.1038/s41576-019-0113-7 | This paper describes the clinical validation of an mNGS assay for diagnosis of meningitis and encephalitis from cerebrospinal fluid |
10.1126/scitranslmed.3004129 | 62,213,468 | Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing revealed its origin and probable modes of transmission. | 10.1038/s41576-019-0113-7 | This study is the first to demonstrate the potential of whole-genome bacterial sequencing using NGS to track transmission of a hospital outbreak of carbapenem-resistant K. pneumoniae |
10.1101/gr.171934.113 | 80,272,868 | Unbiased next-generation sequencing (NGS) approaches enable comprehensive pathogen detection in the clinical microbiology laboratory and have numerous applications for public health surveillance, outbreak investigation, and the diagnosis of infectious diseases. However, practical deployment of the technology is hindere... | 10.1038/s41576-019-0113-7 | This paper describes the sequence-based ultrarapid pathogen identification metagenomic analysis pipeline for use in infectious disease diagnostics |
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/s41576-019-0113-7 | This paper describes the discovery of a novel polyomavirus associated with a rare skin cancer using NGS |
10.1242/jcs.166157 | 40,430,574 | ABSTRACT Pluripotent embryonic stem cells (ESCs) exert low-traction forces on their niche in vitro whereas specification to definitive endoderm in vivo coincides with force-mediated motility, suggesting a differentiation-mediated switch. However, the onset of contractility and extent to which force-mediated integrin si... | 10.1038/s41580-022-00472-z | This study shows that high traction forces and high contractility promote definitive endoderm specification in mouse PSCs |
10.1038/s41467-018-03157-4 | 107,223,250 | Abstract Gut microbiota dysbiosis and metabolic dysfunction in infancy precedes childhood atopy and asthma development. Here we examined gut microbiota maturation over the first year of life in infants at high risk for asthma (HR), and whether it is modifiable by early-life Lactobacillus supplementation. We performed a... | 10.1038/s41577-020-00420-y | This study shows that early-life gut microbial development is distinct but plastic in infants at high risk of asthma |
10.1111/all.13257 | 19,051,292 | Abstract Asthma is responsible for approximately 25,000 deaths annually in Europe despite available medicines that maintain asthma control and reduce asthma exacerbations. Better treatments are urgently needed for the control of chronic asthma and reduction in asthma exacerbations, the major cause of asthma mortality. ... | 10.1038/s41577-020-00420-y | This review article from the EAACI Anti-infectives in Asthma and Asthma Exacerbations Task Force summarizes the potential of anti-infectives and immunomodulators in asthma |
10.1002/pip.892 | 20,596,005 | Abstract The first silicon solar cell was reported in 1941 and had less than 1% energy conversion efficiency compared to the 25% efficiency milestone reported in this paper. Standardisation of past measurements shows there has been a 57% improvement between confirmed results in 1983 and the present result. The features... | 10.1038/s41560-019-0463-6 | Outlines the historical development of silicon solar cell , with specific reference to the PERC cells that continue to hold the efficiency record for silicon devices with heavily dope , directly metallized contacts |
10.1063/1.96331 | 83,114,541 | For maximal performance solar cells should resemble semiconductor lasers, i.e., they should be constructed in the form of a double heterostructure. We have found rather good performance in SIPOS-crystalline silicon-SIPOS double heterostructure solar cells, where SIPOS≡SiOx. The processing of these solar cells gives ins... | 10.1038/s41560-019-0463-6 | Early demonstration of the surface passivation potential of doped poly-silicon or SIPOS-based contacts which would form the basis of extensive recent research for example in so-called TOPCon contacts |
10.1063/1.90646 | 26,444,130 | Major new results are reported for silicon MIS solar cells. Open-circuit voltages up to 655 mV (AM0, 25 °C) have been obtained for 0.1-Ω cm silicon wafers, substantially higher than previously reported for any other silicon solar cell. On an active-area basis, the efficiency of these high-output-voltage cells is close ... | 10.1038/s41560-019-0463-6 | Early demonstration of an archetypal silicon passivating contact solar cell using a thin silicon oxide layer to separate the absorber material from the metal contact resulting in a record open circuit voltage at the time of publication |
10.1063/1.4868880 | 103,800,953 | We explore substoichiometric molybdenum trioxide (MoOx, x < 3) as a dopant-free, hole-selective contact for silicon solar cells. Using an intrinsic hydrogenated amorphous silicon passivation layer between the oxide and the silicon absorber, we demonstrate a high open-circuit voltage of 711 mV and power conversio... | 10.1038/s41560-019-0463-6 | Exemplary dopant-free hole contact—common in organic electronics—applied to silicon, spurring further research into MoO x and other high/low work function, dopant free materials, including other transition metal oxides |
10.1126/science.1214935 | 125,167,861 | Enduring Tolerance During an infection, the host organism deploys multiple defense strategies. Disease resistance, the process by which the immune system decreases pathogen burden is perhaps the most well-known, and certainly the mechanism that is best studied and understood. Other defense strategies range from pathoge... | 10.1038/s41577-020-0301-x | This review introduces the concept of disease tolerance as a mechanism of host defence |
10.1126/science.aai8132 | 125,163,065 | Local macrophage clean-up Infection, especially by helminths or bacteria, can cause tissue damage (see the Perspective by Bouchery and Harris). Minutti et al. studied mouse models of helminth infection and fibrosis. They expressed surfactant protein A (a member of the complement component C1q family) in the lung, which... | 10.1038/s41577-020-0301-x | This study shows that apoptotic neutrophils synergize with type 2 cytokines to activate macrophages to adopt tissue repair properties |
10.1038/s41467-019-09982-5 | 104,343,575 | Abstract Many chromatin features play critical roles in regulating gene expression. A complete understanding of gene regulation will require the mapping of specific chromatin features in small samples of cells at high resolution. Here we describe Cleavage Under Targets and Tagmentation (CUT&Tag), an enzyme-tetherin... | 10.1038/s41587-022-01596-5 | This paper introduced the protein A–Tn5 transposase fusion protein for single-cell and low-input bulk profiling of histone modifications. |
10.1126/science.aax9553 | 104,365,050 | The social environment, both in early life and adulthood, is one of the strongest predictors of morbidity and mortality risk in humans. Evidence from long-term studies of other social mammals indicates that this relationship is similar across many species. In addition, experimental studies show that social interactions... | 10.1038/s41574-022-00746-8 | This paper demonstrates strong parallels in the consequences of social adversity between humans and other social mammals, and reviews studies in experimental animal models that show socially induced stress is, by itself, sufficient to damage health and shorten lifespan |
10.1111/acel.12778 | 20,690,853 | Summary Stress and low socioeconomic status in humans confer increased vulnerability to morbidity and mortality. However, this association is not mechanistically understood nor has its causation been explored in animal models thus far. Recently, cellular senescence has been suggested as a potential mechanism linking li... | 10.1038/s41574-022-00746-8 | A mouse model that demonstrates the adverse effect of subordinate social status on lifespan, implicating cellular senescence in ageing-associated diseases |
10.1126/science.aah3580 | 41,678,409 | Status alters immune function in macaques Rhesus macaques experience variable levels of stress on the basis of their position in the social hierarchy. To examine how stress affects immune function, Snyder-Mackler et al. manipulated the social status of individual macaques (see the Perspective by Sapolsky). Social statu... | 10.1038/s41574-022-00746-8 | By manipulating the social status of individual macaques this animal study examined how stress affects immune function, demonstrating that social status influences the immune system at multiple levels, from immune cell numbers to gene expression and signalling pathways |
10.1073/pnas.1118355109 | 62,221,643 | We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to down-regulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline anti... | 10.1038/s41574-022-00746-8 | The paper describes two viral challenge studies among people with and without stress, and provides support for the concept that prolonged exposure to a stressor can result in glucocorticoid receptor resistance and dysregulation of immune function, potentially contributing to the onset and progression of a wide range of... |
10.2337/dc13-2936 | 102,391,729 | OBJECTIVE The status of psychosocial stress at work as a risk factor for type 2 diabetes is unclear because existing evidence is based on small studies and is subject to confounding by lifestyle factors, such as obesity and physical inactivity. This collaborative study examined whether stress at work, defined as “job s... | 10.1038/s41574-022-00746-8 | In this individual participant meta-analysis of 124,808 adults without diabetes mellitus from 13 European cohort studies, job strain was associated with a 1.15-fold increased risk of incident T2DM, with no evidence of differences in the association by sex |
10.1002/cne.902730303 | 18,128,881 | Abstract We have employed immunohistochemical and morphometric procedures to study the distribution of monoamine‐synthesizing neurons in the medulla oblongata of the adult human, utilizing antibodies to tyrosine hydroxylase (TH), phenylethanolamine N‐methyltransferase (PNMT), and phenylalanine hydroxylase (PH8). In the... | 10.1038/s41583-019-0151-3 | This article presents the first immunohistological characterization of 5-HT neurons in the human medulla |
10.1002/cne.903010202 | 82,155,215 | Abstract Serial 50 μm Nissl‐stained sections through the midbrain and pontine central gray of four adult humans (mean age 56 years, mean postmortem delay 3 hours) were analysed and the subnuclei of the dorsal raphe nucleus (DR) delineated on the basis of neuronal morphology and density. Five subnuclei were apparent: th... | 10.1038/s41583-019-0151-3 | This paper presents one of the first immunohistological characterizations of 5-HT neurons in the human DR |
10.1002/syn.890070407 | 102,807,402 | Abstract We have employed immunohistochemical and morphometric procedures to study serotonin‐synthesizing (PH8‐immunoreactive) neurons in the pontine reticular formation of the adult human. PH8‐immunoreactive neurons were found in three cytoarchitectural regions: the median rahpe nucleus (MnR), oral pontine reticular n... | 10.1038/s41583-019-0151-3 | This article presents one of the first immunohistological characterizations of 5-HT neurons in the human MR |
10.1046/j.1365-2826.2002.00861.x | 42,543,745 | Abstract Serotonergic systems play an important role in the regulation of behavioural, autonomic and endocrine responses to stressful stimuli. This includes modulation of both the hypothalamic‐pituitary‐adrenal (HPA) axis and the hypothalamic‐spinal‐adrenal (HSA) axis, which converge at the level of the adrenal cortex ... | 10.1038/s41583-019-0151-3 | This influential perspective article hypothesizes the existence of topographically organized functionally distinct 5-HT subsystems |
10.1073/pnas.0504510102 | 41,662,510 | Serotonin (5HT) is a critical modulator of neural circuits that support diverse behaviors and physiological processes, and multiple lines of evidence implicate abnormal serotonergic signaling in psychiatric pathogenesis. The significance of 5HT underscores the importance of elucidating the molecular pathways involved i... | 10.1038/s41583-019-0151-3 | This paper describes the development of two Pet1–Cre driver mouse lines, allowing for genetic access to 5-HT neurons, either constitutively or in a tamoxifen-inducible manner |
10.1152/jn.00744.2003 | 79,370,237 | The dorsal (DR) and median raphe (MR) nuclei contain 5-hydroxytryptamine (serotonin, 5-HT) cell bodies that give rise to the majority of the ascending 5-HT projections to the forebrain limbic areas that control emotional behavior. In the past, the electrophysiological identification of neurochemically identified 5-HT n... | 10.1038/s41583-019-0151-3 | This study is one of the earliest to show the electrophysiological diversity of 5-HT neurons using patch clamp recordings in acute brain slices |
10.1111/j.1460-9568.2006.05276.x | 103,877,976 | Abstract Recent electrophysiological studies have discovered evidence of heterogeneity of 5‐hydroxytryptamine (5‐HT) neurons in the mesencephalic raphe nuclei. Of particular interest is a subpopulation of putative 5‐HT neurons that display many of the electrophysiological properties of presumed 5‐HT‐containing neurons ... | 10.1038/s41583-019-0151-3 | This study is one of the first to demonstrate distinct subtypes of 5-HT neurons on the basis of in vivo firing properties |
10.1126/science.1205295 | 4,905,684 | Inducible neuron inhibition reveals essential roles for serotonergic neurons in respiratory and body temperature homeostasis. | 10.1038/s41583-019-0151-3 | This is the first published study to use chemogenetics to study the in vivo functions of 5-HT neurons |
10.1073/pnas.2009316117 | 19,213,950 | In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characteriza... | 10.1038/s41576-021-00416-x | This study uncovers a direct interaction between the RFTS domain of DNMT1 and H3K9me3 |
10.1002/gene.10168 | 59,999,174 | Abstract Summary: Genome‐wide epigenetic reprogramming by demethylation occurs in early mouse embryos and primordial germ cells. In early embryos many single‐copy sequences become demethylated both by active and passive demethylation, whereas imprinted gene methylation remains unaffected. In primordial germ cells singl... | 10.1038/s41576-021-00416-x | This study is the first of many to show that specific TEs are resistant to DNA demethylation during epigenetic reprogramming in germ cells and the pre-implantation embryo |
10.1101/gr.133728.111 | 62,408,061 | Cross-talk between DNA methylation and histone modifications drives the establishment of composite epigenetic signatures and is traditionally studied using correlative rather than direct approaches. Here, we present sequential ChIP-bisulfite-sequencing (ChIP-BS-seq) as an approach to quantitatively assess DNA methylati... | 10.1038/s41576-021-00416-x | Using sequential ChIP-bisulfite sequencing, this study shows that H3K27me3 and DNAme are mutually exclusive at CGIs. In addition, it reveals altered H3K27me3 levels in Dnmt triple-knockout mESCs, indicating an antagonistic relationship between H3K27me3 and DNAme |
10.1073/pnas.1819029116 | 104,367,986 | Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2), the enzyme that catalyzes monomethylation, dimethylation, and trimethylation of lysine 27 on histone H3 (H3K27). Trimethylation at H3K27 (H3K27me3) is associated with transcriptional silencing of developmentally importan... | 10.1038/s41576-021-00416-x | This study demonstrates that EZH2 can sense the H3K36 methylation state, with unmodified H3K36 promoting PRC2 enzymatic activity towards H3K27 |
10.1126/sciadv.aau5935 | 83,398,178 | A methionine substitution at lysine-27 on histone H3 variants (H3K27M) characterizes ~80% of diffuse intrinsic pontine gliomas (DIPG) and inhibits polycomb repressive complex 2 (PRC2) in a dominant-negative fashion. Yet, the mechanisms for this inhibition and abnormal epigenomic landscape have not been resolved. Using ... | 10.1038/s41576-021-00416-x | This study shows that the loss of H3K27me3 observed in diffuse intrinsic pontine gliomas that harbour the H3K27M mutation is accompanied by a gain in H3K36me2 |
10.1126/science.1159292 | 83,477,549 | The ability to maintain interactions between soluble protein subunits in the gas phase of a mass spectrometer gives critical insight into the stoichiometry and interaction networks of protein complexes. Conversely, for membrane protein complexes in micelles, the transition into the gas phase usually leads to the disrup... | 10.1038/s41589-020-0574-1 | This is a report of a membrane protein complex ejected from a detergent micelle into the gas phase of a mass spectrometer with cytoplasmic and membrane domains intact |
10.1126/science.289.5480.739 | 41,560,733 | Heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structural features, including a bundle of seven transmembrane α helices connected by six loops of varying lengths. We determined the struc... | 10.1038/s41589-020-0574-1 | This study reports the structure of an unmodified wild-type GPCR, allowing insights into the propagation of signals in vision |
10.1038/ncomms4912 | 37,755,479 | Abstract Fusogens are membrane proteins that remodel lipid bilayers to facilitate membrane merging. Although several fusogen ectodomain structures have been solved, structural information on full-length, natively membrane-anchored fusogens is scarce. Here we present the electron cryo microscopy three-dimensional recons... | 10.1038/s41589-020-0574-1 | This study reports the cryo-EM structure of a cell–cell fusogen imaged while in a membrane environment |
10.1126/science.aau0976 | 104,299,566 | Membrane proteins reside in lipid bilayers and are typically extracted from this environment for study, which often compromises their integrity. In this work, we ejected intact assemblies from membranes, without chemical disruption, and used mass spectrometry to define their composition. From Escherichia coli outer mem... | 10.1038/s41589-020-0574-1 | This paper reports a mass spectrometry study of membrane protein complexes ejected directly from their membrane environments including bacterial and mitochnodrial membranes |
10.1126/science.aaz2924 | 20,389,682 | In neurons, the loading of neurotransmitters into synaptic vesicles uses energy from proton-pumping vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases). These membrane protein complexes possess numerous subunit isoforms, which complicates their analysis. We isolated homogeneous rat brain V-ATPase through ... | 10.1038/s41589-020-0574-1 | This study reports the cryo-EM structure of the V-type ATPase isolated from rat brain synaptic vesicles. MS was used to define the isoform and subunit stoichiometry and composition of the intact V 1 complex |
10.1126/science.abb5940 | 83,462,554 | Hybrid organic-inorganic perovskites have high potential as materials for solar energy applications, but their microscopic properties are still not well understood. Atomic-resolution scanning transmission electron microscopy has provided invaluable insights for many crystalline solar cell materials, and we used this me... | 10.1038/s41560-022-01096-5 | The first atomic-scale observation of MHP thin-film microstructures using scanning TEM |
10.1038/s41467-020-17012-y | 20,437,872 | Abstract While grain boundaries (GBs) in conventional inorganic semiconductors are frequently considered as detrimental for photogenerated carrier transport, their exact role remains obscure for the emerging hybrid perovskite semiconductors. A primary challenge for GB-property investigations is that experimentally they... | 10.1038/s41560-022-01096-5 | The first 3D imaging of grain boundary networks in MHP thin film s |
10.1038/ncomms14547 | 83,462,743 | Abstract Organic–inorganic hybrid perovskites are exciting candidates for next-generation solar cells, with CH 3 NH 3 PbI 3 being one of the most widely studied. While there have been intense efforts to fabricate and optimize photovoltaic devices using CH 3 NH 3 PbI 3 , critical questions remain regarding the crystal s... | 10.1038/s41560-022-01096-5 | The first microscopic observation of twin domains in MHP thin films |
10.1126/science.aaa5333 | 62,235,945 | Going toward the grains Great strides have been made in improving the efficiency of organic-inorganic perovskite solar cells. Further improvements are likely to depend on understanding the role of film morphology on charge-carrier dynamics. de Quilettes et al. correlated confocal fluorescence microscopy images with tho... | 10.1038/s41560-022-01096-5 | The first microstructure–property correlated study revealing the detrimental effects of GBs in MHPs |
10.1136/flgastro-2019-101177 | 59,270,680 | Objective To describe the development of the Nottingham liver disease stratification pathway, present a 12-month evaluation of uptake and stratification results, and compare the pathway with current British Society of Gastroenterology (BSG) guidelines. Design A referral pathway between primary and secondary care for th... | 10.1038/s41575-021-00477-7 | A large care pathway for identification and risk stratification of liver disease in a community of over 700,000 people |
10.1136/flgastro-2018-101155 | 123,060,019 | Non-alcoholic fatty liver disease (NAFLD) is a globally prevalent health problem, associated in its more severe forms with increased liver-related and cardiovascular-related morbidity and mortality. We established a multidisciplinary metabolic hepatology clinic in 2014 and have analysed the clinical data to evaluate th... | 10.1038/s41575-021-00477-7 | Evaluation of a multidisciplinary team approach for the management of NAFLD and cardiovascular health |
10.1136/flgastro-2020-101480 | 81,545,876 | Background Non-alcoholic fatty liver disease (NAFLD) is common and is associated with liver-related and cardiovascular-related morbidity. Our aims were: (1) to review the current management of patients with NAFLD attending hospital clinics in North East England (NEE) and assess the variability in care; (2) develop a NA... | 10.1038/s41575-021-00477-7 | Outlining a novel NAFLD ‘care bundle’ to standardize secondary care management and assessing the effect of implementation of the NAFLD care bundle |
10.1111/jdv.14831 | 79,873,061 | Abstract Background Classic Kaposi's sarcoma ( CKS ) occurs predominantly among elderly men and is associated with Kaposi's sarcoma‐associated herpesvirus ( KSHV ). In low‐endemic countries, KSHV infects predominantly men having sex with men ( MSM ). Objectives To describe a cohort of classic Kaposi sarcoma in a low‐en... | 10.1038/s41572-019-0060-9 | This study recognizes a fifth type of KS occurring in MSM without HIV infection |
10.1073/pnas.0408192102 | 62,305,181 | MicroRNAs (miRNAs) are an endogenously encoded class of small RNAs that have been proposed to function as key posttranscriptional regulators of gene expression in a range of eukaryotic species, including humans. The small size of miRNA precursors makes them potentially ideal for use by viruses as inhibitors of host cel... | 10.1038/s41572-019-0060-9 | This article presents the first discovery of KSHV-encoded viral miRNAs |
10.1126/science.1199478 | 61,251,415 | A viral homolog of a host microbial sensor inhibits viral detection by the host and subsequent antiviral immunity. | 10.1038/s41572-019-0060-9 | This article demonstrates that KSHV encodes a viral protein, ORF63, that inhibits inflammasomes |
10.1159/000375165 | 17,941,340 | Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposi's sarcoma (KS) in the world. Despite this, KS diagnosis in the region is based mostly on clinical grounds. Where biopsy is available, it has traditionally been excisional and performed by surgeons, resulting in multiple appointments, follow-up visits... | 10.1038/s41572-019-0060-9 | This study illustrates that skin biopsy, which is often performed only by physicians in settings such as the USA, can be performed safely by non-physicians in sub-Saharan Africa, thereby expanding access to the procedure |
10.1200/jgo.18.12000 | 114,390,312 | Abstract 44 Purpose Despite overt presentation on the skin, most Kaposi’s sarcoma (KS) in Africa is diagnosed too late for treatment to be effective. Training health care workers to recognize KS early can increase knowledge, but is only clinically impactful if providers actually encounter early KS—that is, if patients ... | 10.1038/s41572-019-0060-9 | This paper presents a demonstration of community-based communication strategies to increase awareness of the importance of early detection of KS in sub-Saharan Africa |
10.1093/nar/gkz1171 | 82,826,938 | Abstract Release of phosphorothioate antisense oligonucleotides (PS-ASOs) from late endosomes (LEs) is a rate-limiting step and a poorly defined process for productive intracellular ASO drug delivery. Here, we examined the role of Golgi-endosome transport, specifically M6PR shuttling mediated by GCC2, in PS-ASO traffic... | 10.1038/s41573-021-00162-z | This is one of a series of papers describing protein-mediated PS ASO intracellular trafficking and endosomal release |
10.1093/nar/gkaa299 | 103,613,737 | Abstract Antisense oligonucleotides (ASOs) interact with target RNAs via hybridization to modulate gene expression through different mechanisms. ASO therapeutics are chemically modified and include phosphorothioate (PS) backbone modifications and different ribose and base modifications to improve pharmacological proper... | 10.1038/s41573-021-00162-z | This paper reviews the proteins to which PS ASOs bind and the effects of those interactions on the behaviours of both PS ASOs and the proteins |
10.1093/nar/gku531 | 62,251,671 | Abstract Triantennary N-acetyl galactosamine (GalNAc, GN3), a high-affinity ligand for the hepatocyte-specific asialoglycoprotein receptor (ASGPR), enhances the potency of second-generation gapmer antisense oligonucleotides (ASOs) 6–10-fold in mouse liver. When combined with next-generation ASO designs comprised of sho... | 10.1038/s41573-021-00162-z | This paper shows that GalNAc conjugation dramatically enhances ASO potency in vivo by selective targeting to hepatocytes through the cell-surface asialoglycoprotein receptor |
10.1093/nar/gkz500 | 107,238,373 | Abstract Antisense technology can reduce gene expression via the RNase H1 or RISC pathways and can increase gene expression through modulation of splicing or translation. Here, we demonstrate that antisense oligonucleotides (ASOs) can reduce mRNA levels by acting through the no-go decay pathway. Phosphorothioate ASOs f... | 10.1038/s41573-021-00162-z | This is one of a series of papers describing the designs of PS ASOs that can cause target reduction via non-RNase-H1 mechanisms |
10.1002/ana.21801 | 61,931,741 | Abstract Transcranial magnetic resonance (MR)‐guided high‐intensity focused ultrasound (tcMRgHIFU) implies a novel, noninvasive treatment strategy for various brain diseases. Nine patients with chronic neuropathic pain were treated with selective medial thalamotomies. Precisely located thermal ablations of 4mm in diame... | 10.1038/s41582-020-00418-z | The first report of incisionless surgery using MRgFUS thermoablation in humans, undertaken in patients with chronic pain |
10.1038/s41467-018-04529-6 | 20,686,131 | Abstract Magnetic resonance-guided focused ultrasound in combination with intravenously injected microbubbles has been shown to transiently open the blood–brain barrier, and reduce beta-amyloid and tau pathology in animal models of Alzheimer’s disease. Here, we used focused ultrasound to open the blood–brain barrier in... | 10.1038/s41582-020-00418-z | The first report that transcranial FUS BBBO is safe in people with mild-to-moderate AD |
10.1038/s41467-019-12426-9 | 83,433,233 | Abstract MR-guided focused ultrasound (MRgFUS) is an emerging technology that can accurately and transiently permeabilize the blood-brain barrier (BBB) for targeted drug delivery to the central nervous system. We conducted a single-arm, first-in-human trial to investigate the safety and feasibility of MRgFUS-induced BB... | 10.1038/s41582-020-00418-z | The first study of transcranial FUS BBBO in eloquent cortex in people with ALS, showing that the procedure was safe and technically successful |
10.1158/1078-0432.ccr-18-3643 | 62,583,908 | Abstract Purpose: The blood–brain barrier (BBB) limits the efficacy of drug therapies for glioblastoma (GBM). Preclinical data indicate that low-intensity pulsed ultrasound (LIPU) can transiently disrupt the BBB and increase intracerebral drug concentrations. Patients and Methods: A first-in-man, single-arm, single-cen... | 10.1038/s41582-020-00418-z | This study indicated that the use of an implanted ultrasound device to deliver repeated BBBO during carboplatin administration for recurrent glioblastoma is safe and potentially enhances progression-free survival |
10.1002/ana.25604 | 62,468,646 | It is currently unclear whether the glymphatic system, a brain‐wide interstitial fluid–cerebrospinal fluid exchange described in rodents, exists in humans. Focal blood–brain barrier disruption using magnetic resonance–guided focused ultrasound allows parenchymal penetration of gadobutrol contrast, creating an opportuni... | 10.1038/s41582-020-00418-z | Localized and transient BBB opening using FUS allowed the first in vivo visualization of the glymphatic system in humans |
10.1126/scitranslmed.aau5907 | 61,483,035 | Immunotherapy with chimeric antigen receptor (CAR)–engineered T cells can be effective against advanced malignancies. CAR T cells are “living drugs” that require technologies to enable physicians (and patients) to maintain control over the infused cell product. Here, we demonstrate that the tyrosine kinase inhibitor da... | 10.1038/s41576-021-00329-9 | This article reports a pharmacological approach to modulating T cell function in vivo |
10.1158/1078-0432.ccr-16-1300 | 38,445,662 | Abstract Purpose: Using gene-disrupted allogeneic T cells as universal effector cells provides an alternative and potentially improves current chimeric antigen receptor (CAR) T-cell therapy against cancers and infectious diseases. Experimental Design: The CRISPR/Cas9 system has recently emerged as a simple and efficien... | 10.1038/s41576-021-00329-9 | The authors describe a CRISPR–Cas9-based triple knockout of genes encoding TCR, β2M and PD1 in primary human T cells |
10.1126/sciimmunol.aaw4341 | 84,373,433 | Bacterial dysbiosis is associated with Crohn’s disease (CD), a chronic intestinal inflammatory disorder thought to result from an abnormal immune response against intestinal bacteria in genetically susceptible individuals. However, it is unclear whether dysbiosis is a cause or consequence of intestinal inflammation and... | 10.1038/s41577-019-0268-7 | This paper shows that a specific pathobiont can accumulate before the development of intestinal inflammation and trigger spontaneous Crohn’s disease-like colitis in genetically susceptible mice |
10.1126/science.aaw7479 | 38,305,247 | Intestinal adaptive immune responses influence host health, yet only a few intestinal bacteria species that induce cognate adaptive immune responses during homeostasis have been identified. Here, we show that Akkermansia muciniphila , an intestinal bacterium associated with systemic effects on host metabolism and PD-1 ... | 10.1038/s41577-019-0268-7 | This paper shows that A. muciniphila -specific T cells differentiate into T follicular helper cells to generate homeostatic IgG1 in gnotobiotic animals but can also adopt multiple T H cell lineages in mice with a complex microbiota |
10.1042/bj1850775 | 41,569,295 | In a search for new inhibitors of the nuclear enzyme poly(ADP-ribose) synthetase, it was found that various benzamides substituted in the 3-position were the most inhibitory compounds found to date. Two of the benzamides, 3-aminobenzamide and 3-methoxybenzamide, were found to be competitive inhibitors, with Ki values o... | 10.1038/s41573-020-0076-6 | This study describes the synthesis of the first PARP inhibitor, 3-AB |
10.1101/gad.9.5.509 | 19,882,169 | Poly(ADP-ribosyl)ation is catalyzed by NAD+: protein(ADP-ribosyl) transferase (ADPRT), a chromatin-associated enzyme which, in the presence of DNA breaks, transfers ADP-ribose from NAD+ to nuclear proteins. This post-translational modification has been implicated in many fundamental processes, like DNA repair, chromati... | 10.1038/s41573-020-0076-6 | This study describes the generation of the Parp1 -knockout mouse |
10.1073/pnas.93.5.1753 | 18,810,523 | The free radicals nitric oxide and superoxide anion react to form peroxynitrite (ONOO-), a highly toxic oxidant species. In vivo formation of ONOO- has been demonstrated in shock and inflammation. Herein we provide evidence that cytotoxicity in cells exposed to ONOO- is mediated by DNA strand breakage and the subsequen... | 10.1038/s41573-020-0076-6 | This study describes how PARP activation occurs in response to nitrosative stress and also describes the protective effect of PARP inhibition against cell death |
10.1073/pnas.94.6.2261 | 122,098,560 | Mammalian cells contain activities that amplify the effects of activators on class II gene transcription in vitro . The molecular identity of several of these cofactor activities is still unknown. Here we identify poly(ADP-ribose) polymerase (PARP) as one functional component of the positive cofactor 1 activity. PARP e... | 10.1038/s41573-020-0076-6 | This study is the first to link PARP to gene transcription events |
10.4049/jimmunol.161.7.3753 | 139,071,276 | Abstract Reactive oxidant species are important mediators of tissue injury in shock, inflammation, and reperfusion injury. The actions of a number of these oxidants (e.g., hydroxyl radical and peroxynitrite, a reactive oxidant produced by the reaction of nitric oxide and superoxide) are mediated in part by the activati... | 10.1038/s41573-020-0076-6 | This study shows PARP overactivation promotes a regulated form of cell necrosis in oxidatively stressed cells |
10.1073/pnas.0606526103 | 41,681,387 | Excessive activation of the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) plays a prominent role in various of models of cellular injury. Here, we identify poly(ADP-ribose) (PAR) polymer, a product of PARP-1 activity, as a previously uncharacterized cell death signal. PAR polymer is directly toxic to neurons, ... | 10.1038/s41573-020-0076-6 | This study is the first to recognize PAR as an independent mediator of cell death |
10.1158/1078-0432.ccr-08-1223 | 18,432,885 | Abstract Purpose: One mechanism of tumor resistance to cytotoxic therapy is repair of damaged DNA. Poly(ADP-ribose) polymerase (PARP)-1 is a nuclear enzyme involved in base excision repair, one of the five major repair pathways. PARP inhibitors are emerging as a new class of agents that can potentiate chemotherapy and ... | 10.1038/s41573-020-0076-6 | This article describes the first clinical trial of a PARP inhibitor, in which rucaparib was evaluated in combination with temozolomide |
10.1158/1078-0432.ccr-09-2758 | 19,365,644 | Abstract Purpose: Poly(ADP-ribose) polymerase (PARP) inhibitors selectively target homologous recombination (HR)–defective cells and show good clinical activity in hereditary breast and ovarian cancer associated with BRCA1 or BRCA2 mutations. A high proportion (up to 50%) of sporadic epithelial ovarian cancers (EOC) co... | 10.1038/s41573-020-0076-6 | This is the first demonstration that more than 50% of ovarian cancers are HRR defective |
10.1079/searchrxiv.2023.00130 | 137,789,178 | Abstract To access clinical trials assessing efficacy of Niraparib-bevacizumab combination maintenance therapy in patients with Ovarian Carcinoma. | 10.1038/s41573-020-0076-6 | This study describes the clinical trial leading to the first approval of niraparib |
10.1158/0008-5472.can-18-1003 | 103,761,501 | Abstract PARP inhibitors (PARPi) have shown remarkable therapeutic efficacy against BRCA1/2-mutant cancers through a synthetic lethal interaction. PARPi exert their therapeutic effects mainly through the blockade of ssDNA damage repair, which leads to the accumulation of toxic DNA double-strand breaks specifically in c... | 10.1038/s41573-020-0076-6 | This study demonstrates the therapeutic potential of a PARP inhibitor in combination with immune checkpoint blockade |
10.1158/0008-5472.can-09-1178 | 101,973,817 | Abstract Acquired platinum resistance is a serious problem in the treatment of ovarian carcinomas. However, the mechanism of the drug resistance has not been elucidated. Here, we show functional significance of restoration of BRCA2 protein by secondary BRCA2 mutations in acquired drug resistance of BRCA2-mutated ovaria... | 10.1038/s41573-020-0076-6 | This study identifies secondary mutations in BRCA2 that restore BRCA2 function |
10.1126/science.1231143 | 104,401,399 | Genome Editing Clustered regularly interspaced short palindromic repeats (CRISPR) function as part of an adaptive immune system in a range of prokaryotes: Invading phage and plasmid DNA is targeted for cleavage by complementary CRISPR RNAs (crRNAs) bound to a CRISPR-associated endonuclease (see the Perspective by van d... | 10.1038/s41573-022-00476-6 | References 54–56 are three landmark studies describing the development of the CRIPSR–Cas platform for programmable genome editing applications |
10.1126/scitranslmed.aac4964 | 45,531,877 | Implantable designer cells sense proinflammatory cytokines and coordinate production and delivery of anti-inflammatory molecules to attenuate psoriasis in mice. | 10.1038/s41573-022-00476-6 | This study is one of the first examples of closed-loop sense-and-respond circuitry that enables cells to sense disease-associated environmental cues and therapeutically respond |
10.1126/science.aaf4006 | 124,750,099 | Engineering cells to regulate glucose Diabetes mellitus affects hundreds of millions of people worldwide. Blood glucose levels are chronically deregulated in diabetics, and this can lead to many serious disorders, including cardiovascular disease and renal failure. Xie et al. engineered a synthetic circuit into human c... | 10.1038/s41573-022-00476-6 | This study harnesses ion channels to engineer encapsulated cell devices that are capable of treating glycaemia in an in vivo model |
10.1038/s41467-019-14147-5 | 103,370,779 | Abstract Engineering mammalian cells to carry out sophisticated and customizable genetic programs requires a toolkit of multiple orthogonal and well-characterized transcription factors (TFs). To address this need, we develop the COmposable Mammalian Elements of Transcription (COMET)—an ensemble of TFs and promoters tha... | 10.1038/s41573-022-00476-6 | References 131 and 132 describe a highly modular ZF transcription factor-based gene circuit engineering platform, and demonstrate its scalability to engineering complex circuit architetures in yeast and human cells |
10.1126/sciadv.abm1032 | 136,143,616 | Proinflammatory cytokines have been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects that limit long-term benefits. To overcome t... | 10.1038/s41573-022-00476-6 | This study demonstrates programmable and localized immunomodulation through cell-generated cytokines |
10.1126/science.aad5227 | 20,680,038 | Making the correct cut The CRISPR/Cas system is a prokaryotic immune system that targets and cuts out foreign DNA in bacteria. It has been adopted for gene editing because it can be designed to recognize and cut specific locations in the genome. A challenge in developing clinical applications is the potential for off-t... | 10.1038/s41573-022-00476-6 | References 257 and 258 highlight engineering efforts resulting in Cas9 proteins with improved specificity profiles in human cells |
10.1210/clinem/dgab775 | 130,258,968 | Abstract Context A genetic etiology likely accounts for the majority of unexplained primary ovarian insufficiency (POI). Objective We hypothesized that heterozygous rare variants and variants in enhanced categories are associated with POI. Design The study was an observational study. Setting Subjects were recruited at ... | 10.1038/s41591-022-02196-1 | This paper reports the results of WES from 291 patients with POI. |
10.1101/gad.1158803 | 41,626,429 | MicroRNAs (miRNAs) are initially expressed as long transcripts that are processed in the nucleus to yield ∼65-nucleotide (nt) RNA hairpin intermediates, termed pre-miRNAs, that are exported to the cytoplasm for additional processing to yield mature, ∼22-nt miRNAs. Here, we demonstrate that human pre-miRNA nuclear expor... | 10.1038/s41580-018-0059-1 | References 16–18 identify Exp5 as the export receptor that is required for exporting pre-miRNAs into the cytoplasm |
10.1101/gad.927801 | 20,678,269 | Double-stranded RNAs can suppress expression of homologous genes through an evolutionarily conserved process named RNA interference (RNAi) or post-transcriptional gene silencing (PTGS). One mechanism underlying silencing is degradation of target mRNAs by an RNP complex, which contains ∼22 nt of siRNAs as guides to subs... | 10.1038/s41580-018-0059-1 | References 19 and 20 identify Dicer as the RNase III enzyme that further processes pre-miRNAs into mature miRNAs |
10.1126/science.1121638 | 103,800,146 | The specialized ribonuclease Dicer initiates RNA interference by cleaving double-stranded RNA (dsRNA) substrates into small fragments about 25 nucleotides in length. In the crystal structure of an intact Dicer enzyme, the PAZ domain, a module that binds the end of dsRNA, is separated from the two catalytic ribonuclease... | 10.1038/s41580-018-0059-1 | This paper presents the crystallization of Dicer from G. intestinalis , which provides molecular details of Dicer function |
10.1038/s41408-022-00719-0 | 141,876,234 | Abstract Smoldering multiple myeloma (SMM) is an asymptomatic condition that occupies a space between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) along the spectrum of clonal plasma cell proliferative disorders. It is not a biologic intermediate stage between MGUS and MM, but rat... | 10.1038/s41591-022-02187-2 | A review article that presents arguments in support of the treatment of SMM. |
10.1182/blood.2021011670 | 130,025,660 | Abstract The current standard of care in smoldering multiple myeloma (SMM) is close surveillance, outside of clinical trials. Efforts are being made to understand the pathobiologic process that leads to the progression of SMM to active MM. This review provides a critical description of available data, including risk fa... | 10.1038/s41591-022-02187-2 | A review article that presents arguments against the treatment of SMM. |
10.1029/2004jc002601 | 20,550,217 | Comparison of eight iron experiments shows that maximum Chl a , the maximum DIC removal, and the overall DIC/Fe efficiency all scale inversely with depth of the wind mixed layer (WML) defining the light environment. Moreover, lateral patch dilution, sea surface irradiance, temperature, and grazing play additional roles... | 10.1038/s41467-018-04970-7 | Important synthesis of our understanding of nutrient limitation in the ocean |
10.1139/a01-012 | 83,290,131 | An accurate and complete emission inventory for atmospheric trace metals on a global scale is needed for both modeler community and policy makers to assess the current level of environmental contamination by these pollutants, major emission sources and source regions, and the contribution of the atmospheric pathway to ... | 10.1038/s41467-018-04970-7 | Globally averaged assessment of trace metals in aerosols from anthropogenic sources |
10.5194/bg-12-5771-2015 | 29,119,068 | Abstract. Trace element deposition from desert dust has important impacts on ocean primary productivity, the quantification of which could be useful in determining the magnitude and sign of the biogeochemical feedback on radiative forcing. However, the impact of elemental deposition to remote ocean regions is not well ... | 10.1038/s41467-018-04970-7 | Study which resolved the spatial variability in elemental distributions in dust |
10.1101/gad.284430.116 | 122,645,682 | The coordinated regulation of gene expression at the transcriptional level is fundamental to development and homeostasis. Inducible systems are invaluable when studying transcription because the regulatory process can be triggered instantaneously, allowing the tracking of ordered mechanistic events. Here, we use precis... | 10.1038/s41576-018-0001-6 | This study demonstrates that pausing is an indispensable step for heat-induced transcription and maps the global transcriptional changes in heat-stressed cells. |
10.1038/s41467-017-00151-0 | 38,953,063 | Abstract Programs of gene expression are executed by a battery of transcription factors that coordinate divergent transcription from a pair of tightly linked core initiation regions of promoters and enhancers. Here, to investigate how divergent transcription is reprogrammed upon stress, we measured nascent RNA synthesi... | 10.1038/s41576-018-0001-6 | This report quantifies transcriptional changes at nucleotide resolution across genes and enhancers in human cells, identifying mechanisms that establish directionality and prewire transactivation. |
10.1126/science.1156093 | 20,713,705 | Temperature pervasively affects all cellular processes. In response to a rapid increase in temperature, all cells undergo a heat shock response, an ancient and highly conserved program of stress-inducible gene expression, to reestablish cellular homeostasis. In isolated cells, the heat shock response is initiated by th... | 10.1038/s41576-018-0001-6 | This study identifies organismal control over cellular stress responses in |
10.1101/gad.293118.116 | 62,167,542 | Activation of transcription requires alteration of chromatin by complexes that increase the accessibility of nucleosomal DNA. Removing nucleosomes from regulatory sequences has been proposed to play a significant role in activation. We tested whether changes in nucleosome occupancy occurred on the set of genes that is ... | 10.1038/s41576-018-0001-6 | This paper shows globally increased chromatin accessibility and nucleosome remodelling at stress-induced genes. |
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