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10.1111/j.1464-5491.2011.03246.x | 20,232,381 | Diabet. Med. 28, 508–515 (2011) Abstract The Joint British Diabetes Societies guidelines for the management of diabetic ketoacidosis (these do not cover Hyperosmolar Hyperglycaemic Syndrome) are available in full at: http://www.diabetes.org.uk/About_us/Our_Views/Care_recommendations/The‐Management‐of‐Diabetic‐Ketoacido... | 10.1038/s41572-020-0165-1 | This manuscript describes the current guidelines from the UK and these remain amongst the most used in the world for adults |
10.7554/elife.29808 | 81,081,493 | The locus coeruleus (LC) projects throughout the brain and spinal cord and is the major source of central noradrenaline. It remains unclear whether the LC acts functionally as a single global effector or as discrete modules. Specifically, while spinal-projections from LC neurons can exert analgesic actions, it is not k... | 10.1038/s41583-020-0360-9 | This study reveals the modular organization of LC with projection and behaviour-specific cell populations |
10.1073/pnas.1320827111 | 101,865,266 | Significance The locus coeruleus projection system in the brain is thought to exert uniform and synchronous modulatory effects on cells and circuits throughout the CNS by widespread release of its transmitter, norepinephrine. We challenge this notion by demonstrating that neurons in the locus coeruleus maintain segrega... | 10.1038/s41583-020-0360-9 | This comprehensive study uses anatomical, molecular and electrophysiological approaches to demonstrate the heterogeneity of LC cell populations projecting to prefrontal or motor cortices |
10.1146/annurev.neuro.28.061604.135709 | 104,345,995 | Historically, the locus coeruleus-norepinephrine (LC-NE) system has been implicated in arousal, but recent findings suggest that this system plays a more complex and specific role in the control of behavior than investigators previously thought. We review neurophysiological and modeling studies in monkey that support a... | 10.1038/s41583-020-0360-9 | The authors present a computational approach to modelling the relation between mode of firing of LC neurons and adaptive behavioural performance |
10.1038/s41396-017-0010-z | 104,284,761 | Abstract A bean bug symbiont, Burkholderia sp. RPE64, selectively colonizes the gut crypts by flagella-mediated motility: however, the mechanism for this colonization remains unclear. Here, to obtain clues to this mechanism, we characterized the swimming motility of the Burkholderia symbiont under an advanced optical m... | 10.1038/s41579-019-0182-9 | This paper provides a description of the recently discovered corkscrew motility mode in insect and squid symbionts |
10.1126/science.1219417 | 123,176,373 | Ocean Monarchs It is hard to grasp that the unseen microorganisms of the oceans are the most productive on the planet, at orders of magnitude greater than sharks and whales or even terrestrial forests. The plankton is thus a major contributor to the geochemical cycles that are currently under pressure from climate chan... | 10.1038/s41579-019-0182-9 | This is a modelling study that illustrates how turbulent fluid motion gives rise to small-scale heterogeneity and chemical gradients |
10.1073/pnas.1618584114 | 103,814,057 | Plant roots play a dominant role in shaping the rhizosphere, the environment in which interaction with diverse microorganisms occurs. Tracking the dynamics of root–microbe interactions at high spatial resolution is currently limited because of methodological intricacy. Here, we describe a microfluidics-based approach e... | 10.1038/s41579-019-0182-9 | This is a recent study imaging root–bacterial interactions at previously unattainable spatiotemporal resolutions |
10.1073/pnas.1511454112 | 41,698,861 | Symbiosis has significantly contributed to organismal adaptation and diversification. For establishment and maintenance of such host–symbiont associations, host organisms must have evolved mechanisms for selective incorporation, accommodation, and maintenance of their specific microbial partners. Here we report the dis... | 10.1038/s41579-019-0182-9 | This study provides a fascinating example of an overlooked mechanism enabling symbiont selection |
10.1029/2012jd018015 | 45,302,593 | The predictability of daily temperature and precipitation extremes is assessed out to a decade ahead using the Met Office Decadal Prediction System. Extremes are defined using a simple percentile based counting method applied to daily gridded observation data sets and corresponding model forecasts. We investigate moder... | 10.1038/s41558-018-0359-7 | This paper assesses the predictability of daily temperature and precipitation extremes over various timescales (up to a decade), using a state-of-the-art decadal prediction system. When assessing extreme temperature predictions for the season ahead, the study finds modest, but significant, skill over Europe and North A... |
10.5194/gmd-9-3751-2016 | 125,137,598 | Abstract. The Decadal Climate Prediction Project (DCPP) is a coordinated multi-model investigation into decadal climate prediction, predictability, and variability. The DCPP makes use of past experience in simulating and predicting decadal variability and forced climate change gained from the fifth Coupled Model Interc... | 10.1038/s41558-018-0359-7 | This paper describes the upcoming study of decadal prediction under CMIP6. This study will contribute to the issuance of the upcoming Global Annual to Decadal Climate Update by the WCRP GC-NTCP |
10.1038/s41598-021-01714-4 | 133,864,945 | Abstract A growing body of scholarship investigates the role of misinformation in shaping the debate on climate change. Our research builds on and extends this literature by (1) developing and validating a comprehensive taxonomy of climate contrarianism, (2) conducting the largest content analysis to date on contrarian... | 10.1038/s41558-022-01533-z | This paper introduces a computer-aided taxonomy of climate contrarian views, many of which are found in the COP26 minority. |
10.1073/pnas.1517441113 | 62,283,152 | The wide availability of user-provided content in online social media facilitates the aggregation of people around common interests, worldviews, and narratives. However, the World Wide Web (WWW) also allows for the rapid dissemination of unsubstantiated rumors and conspiracy theories that often elicit rapid, large, but... | 10.1038/s41558-022-01533-z | This paper introduces some of the methods that we used to study the infodemic phenomenon on social media. |
10.1002/wcc.569 | 102,973,642 | Social media is a transformative digital technology, collapsing the “six degrees of separation” which have previously characterized many social networks, and breaking down many of the barriers to individuals communicating with each other. Some commentators suggest that this is having profound effects across society, th... | 10.1038/s41558-022-01533-z | This review article gives an overview of the discussion around climate change on social media. |
10.1126/science.1194637 | 20,828,539 | Primitive Origins for Microglia Microglia are the resident macrophages of the central nervous system and are associated with neurodegeneration and brain inflammatory diseases. Although the developmental origins of other tissue macrophage populations are well established, the origins of microglia remain controversial. G... | 10.1038/s41593-018-0145-x | This paper showed that microglia originate from the yolk sac-derived progenitors |
10.1126/science.1110647 | 104,394,772 | Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells... | 10.1038/s41593-018-0145-x | This paper revealed that microglial processes constantly scan their environment. |
10.1126/science.aad8670 | 125,247,953 | Microglia development follows a stepwise program Microglia are cells that defend the central nervous system. However, because they migrate into the brain during development, the changes that they undergo, including those that affect gene expression, have been difficult to document. Matcovitch-Natan et al. transcription... | 10.1038/s41593-018-0145-x | This paper follows the transcriptional and epigenetic profile of microglia throughout development. |
10.1038/s41467-017-00769-0 | 80,282,264 | Abstract During ageing, microglia acquire a phenotype that may negatively affect brain function. Here we show that ageing microglial phenotype is largely imposed by interferon type I (IFN-I) chronically present in aged brain milieu. Overexpression of IFN-β in the CNS of adult wild-type mice, but not of mice lacking IFN... | 10.1038/s41593-018-0145-x | This study showed that aging-induced secretory phenotype of the blood–cerebrospinal fluid barrier negatively affects cognitive ability through the modulation of microglia. |
10.1126/science.aal3222 | 83,303,332 | Of mice and men's microglia Microglia are immune system cells that function in protecting and maintaining the brain. Gosselin et al. examined the epigenetics and RNA transcripts from single microglial cells and observed consistent profiles among samples despite differences in age, sex, and diagnosis. Mouse and human mi... | 10.1038/s41593-018-0145-x | This work compared expression of orthologous genes in human and mouse microglia and demonstrated the effect of culture condition on microglial transcriptional profile. |
10.1093/jbcr/irab032.078 | 18,917,089 | Abstract Introduction Cooking- and cookstove-related burns (CSBs) comprise a large proportion of burn injuries globally. A cookstove is any apparatus that provides heat and is used for cooking (e.g., three-stone fire, traditional or improved cookstove). There are limited data on patterns of cooking behaviors and CSBs t... | 10.1038/s41572-020-0145-5 | A resource that illustrates the creation of a cheap, easy-to-use registry to better understand the epidemiology of burn injuries around the world |
10.1073/pnas.1222878110 | 20,808,647 | A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammat... | 10.1038/s41572-020-0145-5 | This landmark study demonstrates that the genomic response observed in humans to burn injury is highly correlated with that to trauma and simulated sepsis, suggesting that if an intervention targeting the response is effective for one type of insult, it may be effective against all three |
10.1002/adfm.201900455 | 103,641,163 | Abstract Currently, the efficiency of perovskite solar cells (PSCs) is ≈24%. For the fabrication of such high efficiency PSCs, it is necessary to use both electron and hole transport layers to effectively separate the charges generated by light absorption of the perovskite layer and selectively transfer the separated e... | 10.1038/s41578-022-00503-3 | This work provides an up-to-date overview of the development of state-of-the-art metal-oxide charge-transport layers for the fabrication of efficient and stable perovskite solar cells (PSCs). |
10.1002/aenm.201803140 | 122,345,769 | Abstract Lead halide perovskite solar cells have rapidly achieved high efficiencies comparable to established commercial photovoltaic technologies. The main focus of the field is now shifting toward improving the device lifetime. Many efforts have been made to increase the stability of the perovskite compound and charg... | 10.1038/s41578-022-00503-3 | This study analyses materials and interface engineering of charge-selective contacts to enhance the device stability of PSCs. |
10.1126/science.abf5602 | 122,996,078 | Iodine-terminated self-assembled monolayer (I-SAM) was used in perovskite solar cells (PSCs) to achieve a 50% increase of adhesion toughness at the interface between the electron transport layer (ETL) and the halide perovskite thin film to enhance mechanical reliability. Treatment with I-SAM also increased the power co... | 10.1038/s41578-022-00503-3 | This work shows that the insertion of an iodine-terminated self-assembled monolayer (SAM) at the SnO 2 /perovskite interface increases the adhesion toughness between the electron-transport layer (ETL) and perovskite layer by 50%. |
10.1126/sciadv.aao5616 | 83,481,651 | Strain discovered in hybrid perovskite films made by existing methods affects perovskite solar cells’ intrinsic stability. | 10.1038/s41578-022-00503-3 | This study reveals that the thermal expansion mismatch between the perovskite and substrate materials is an important intrinsic source of instability in perovskite films, accelerating the decomposition of PSCs. |
10.1002/aenm.202101662 | 134,781,675 | Abstract Sputtered nickel oxide (NiO x ) is an attractive hole‐transport layer for efficient, stable, and large‐area p‐i‐n metal‐halide perovskite solar cells (PSCs). However, surface traps and undesirable chemical reactions at the NiO x /perovskite interface are limiting the performance of NiO x ‐based PSCs. To addres... | 10.1038/s41578-022-00503-3 | This work provides an insight into the interface modification of the NiO x hole-transport layer (HTL)/perovskite interface by self-assembled N719 dye, and its impact on the fabrication of highly efficient and stable single-junction and multi-junction PSCs. |
10.1002/aenm.202002989 | 124,111,897 | Abstract Due to a certified 25.2% high efficiency, low cost, and easy fabrication; perovskite solar cells (PSCs) are the focus of interest among the next‐generation photovoltaic technologies. Long‐term stability is one of the most challenging obstacles to bring technology from the lab to the market. In this review, app... | 10.1038/s41578-022-00503-3 | This work describes the importance of SAMs for the improvement of PSC performance through energy band alignment, reduced interfacial charge recombination and trap passivation. |
10.1073/pnas.1912459116 | 103,715,196 | The expression profiles and spatial distributions of RNAs regulate many cellular functions. Image-based transcriptomic approaches provide powerful means to measure both expression and spatial information of RNAs in individual cells within their native environment. Among these approaches, multiplexed error-robust fluore... | 10.1038/s41580-021-00356-8 | Example of multiplexed error-robust FISH (MERFISH) demonstrating near-genome-wide, spatially resolved RNA profiling of individual cells |
10.1126/science.280.5363.585 | 41,743,405 | Fluorescence in situ hybridization (FISH) and digital imaging microscopy were modified to allow detection of single RNA molecules. Oligodeoxynucleotide probes were synthesized with five fluorochromes per molecule, and the light emitted by a single probe was calibrated. Points of light in exhaustively deconvolved images... | 10.1038/s41580-021-00356-8 | First demonstration of single mRNA detection in situ by FISH |
10.1126/science.aan2399 | 81,423,236 | Location, location, location The distribution of RNA in cells is important for efficient translation into proteins. Asymmetric RNA localization is known in several cell types but is poorly understood in gut epithelial cells. Moor et al. found that transcripts in intestinal enterocytes tend to distribute to the cells' a... | 10.1038/s41580-021-00356-8 | Shows that, in the intestinal epithelium, mRNA localization contributes to the polarization of the translation machinery, in turn modulating gene expression changes |
10.1126/science.aau3644 | 62,046,546 | There is ample evidence for localization of messenger RNAs (mRNAs) and protein synthesis in neuronal dendrites; however, demonstrations of these processes in presynaptic terminals are limited. We used expansion microscopy to resolve pre- and postsynaptic compartments in rodent neurons. Most presynaptic terminals in the... | 10.1038/s41580-021-00356-8 | Identified hundreds of mRNA molecules and translation machinery in axonal terminals of adult brain, indicating the existence of local protein synthesis in both presynaptic and postsynaptic compartments of neurons |
10.1126/science.aaf1084 | 83,436,516 | The when, where, and how of translation High-resolution single-molecule imaging shows the spatial and temporal dynamics of molecular events (see the Perspective by Iwasaki and Ingolia). Wu et al. and Morisaki et al. developed an approach to study the translation of single messenger RNAs (mRNAs) in live cells. Nascent p... | 10.1038/s41580-021-00356-8 | Together with refs 202,294–296, a first example of an imaging-based single-molecule mRNA translation reporter |
10.1126/science.aay4991 | 122,995,444 | To accommodate their complex morphology, neurons localize messenger RNAs (mRNAs) and ribosomes near synapses to produce proteins locally. However, a relative paucity of polysomes (considered the active sites of translation) detected in electron micrographs of neuronal processes has suggested a limited capacity for loca... | 10.1038/s41580-021-00356-8 | A first-time demonstration of differential monosome-mediated versus polysome-mediated translation in neurons and the preference for monosome-mediated translation in distal processes |
10.1083/jcb.201605024 | 20,671,054 | Translation is an essential step in gene expression. In this study, we used an improved SunTag system to label nascent proteins and image translation of single messenger ribonucleoproteins (mRNPs) in human cells. Using a dedicated reporter RNA, we observe that translation of single mRNPs stochastically turns on and off... | 10.1038/s41580-021-00356-8 | Together with refs 93,294–296, first example of imaging-based single-molecule mRNA translation reporters |
10.1126/science.aaf0899 | 83,435,872 | The when, where, and how of translation High-resolution single-molecule imaging shows the spatial and temporal dynamics of molecular events (see the Perspective by Iwasaki and Ingolia). Wu et al. and Morisaki et al. developed an approach to study the translation of single messenger RNAs (mRNAs) in live cells. Nascent p... | 10.1038/s41580-021-00356-8 | Together with refs 93,202,295,296, first example of imaging-based single-molecule mRNA translation reporter |
10.1084/jem.20110740 | 20,831,504 | Memory B cells (MBCs) and long-lived plasma cells (LLPCs) persist after clearance of infection, yet the specific and nonredundant role MBCs play in subsequent protection is unclear. After resolution of West Nile virus infection in mice, we demonstrate that LLPCs were specific for a single dominant neutralizing epitope,... | 10.1038/s41577-020-00446-2 | This study finds that MBCs, but not plasma cells, can recognize previously unencountered stains of the West Nile virus, suggesting that MBCs might be an important component of heterosubtypic immunity |
10.1084/jem.20142284 | 83,495,234 | Respiratory influenza virus infection induces cross-reactive memory B cells targeting invariant regions of viral escape mutants. However, cellular events dictating the cross-reactive memory B cell responses remain to be fully defined. Here, we demonstrated that lung-resident memory compartments at the site of infection... | 10.1038/s41577-020-00446-2 | This study finds that MBCs in the lungs have an elevated fraction of cross-reactive clones relative to cells in the secondary lymphoid organs after influenza virus infection |
10.1002/art.41511 | 103,700,411 | Objective Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in‐depth understanding of the contribution of gut microbiota to the immunopathogenesis of SLE. Methods Fecal metagenomes from 117 patients with untreated SLE and 52 SLE pat... | 10.1038/s41587-022-01230-4 | Auto-inflammatory bacterial proteins in the guts of patients with lupus mimic human autoantigens |
10.1038/s41594-022-00747-1 | 135,833,459 | Abstract Poly(ADP-ribose) polymerase 1 (PARP1) is implicated in the detection and processing of unligated Okazaki fragments and other DNA replication intermediates, highlighting such structures as potential sources of genome breakage induced by PARP inhibition. Here, we show that PARP1 activity is greatly elevated in c... | 10.1038/s41568-022-00518-6 | This work uncovers the mechanism by which PARPi promotes the formation of ssDNA gaps, which are an emerging determinant of PARPi response in BRCA-deficient cancers |
10.1038/s41586-020-1943-3 | 83,488,365 | Abstract Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1 . Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCG... | 10.1038/s41568-022-00518-6 | This paper provides a comprehensive landscape of tumour mutational signatures and links replication stress response mechanisms with several of these mutational patterns in cancers |
10.1242/dev.137372 | 105,414,498 | ABSTRACT On Thursday 9 May 1991, the world awoke to front-page news of a breakthrough in biological research. From Washington to Wollongong, newspapers, radio and TV were abuzz with the story of a transgenic mouse in London called Randy. Why was this mouse so special? The mouse in question was a chromosomal female (XX)... | 10.1038/s41576-021-00365-5 | This article provides a lively account of the characterization of SRY as the key mammalian gonadal sex determination gene, told by three of the main protagonists |
10.1210/jc.2014-2605 | 107,361,611 | Abstract Context: Disorders of sex development (DSD) are clinical conditions where there is a discrepancy between the chromosomal sex and the phenotypic (gonadal or genital) sex of an individual. Such conditions can be stressful for patients and their families and have historically been difficult to diagnose, especiall... | 10.1038/s41576-021-00365-5 | This article reports an early use of clinical exome sequencing for DSD diagnosis on a cohort of 46,XY individuals with various DSD conditions |
10.1038/s41574-018-0010-8 | 103,804,470 | Abstract The term differences of sex development (DSDs; also known as disorders of sex development) refers to a heterogeneous group of congenital conditions affecting human sex determination and differentiation. Several reports highlighting suboptimal physical and psychosexual outcomes in individuals who have a DSD led... | 10.1038/s41576-021-00365-5 | This consensus statement by European workgroups details approaches and data collection processes for management of individuals with DSD throughout their lifespan |
10.1159/000481896 | 29,191,154 | Despite considerable research effort and significant advances in sequencing technologies, the majority of disorders of sex development (DSD) cases still lack a molecular genetic diagnosis. While coding variants have been discovered in known and candidate DSD genes, comparatively little is known about copy number variat... | 10.1038/s41576-021-00365-5 | This article provides a comprehensive literature review of the impact of structural variants in DSD aetiology |
10.1038/s41467-018-08148-z | 104,327,116 | Abstract The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehe... | 10.1038/s41576-021-00365-5 | This landmark benchmarking study compares the respective outputs of LRS, SRS and OGM data sets for detection of structural variants of various sizes and types on the same genome |
10.1111/j.1399-0039.2011.01820.x | 123,050,880 | Assessment of the host immune status is becoming a key issue in allogeneic hematopoietic stem cell transplantation (allo‐HSCT). In the long‐term follow‐up of these patients, severe post‐transplant infections, relapse or secondary malignancies may be directly related to persistent immune defects. In allo‐HSCT, T‐cell di... | 10.1038/s41577-020-00457-z | This is a detailed review of the role of the thymus in allogeneic HSCT recipients and the use of TRECs to quantify its function |
10.1111/sji.12618 | 4,602,207 | Abstract The thymus is essential for T cell development and maturation. It is extremely sensitive to atrophy, wherein loss in cellularity of the thymus and/or disruption of the thymic architecture occur. This may lead to lower naïve T cell output and limited TCR diversity. Thymic atrophy is often associated with ageing... | 10.1038/s41577-020-00457-z | This review provides an overview of the numerous factors linked to the atrophy of the thymus |
10.1182/blood-2006-07-034157 | 38,208,694 | Abstract Acute graft-versus-host disease (aGVHD) impairs thymus-dependent T-cell regeneration in recipients of allogeneic bone marrow transplants through yet to be defined mechanisms. Here, we demonstrate in mice that MHC-mismatched donor T cells home into the thymus of unconditioned recipients. There, activated donor ... | 10.1038/s41577-020-00457-z | This study investigates the molecular and cellular mechanisms underlying the impact of GVHD on TEC function |
10.1182/blood-2008-01-136531 | 58,412,875 | Abstract Myeloablative conditioning results in thymic epithelial cell (TEC) injury, slow T-cell reconstitution, and a high risk of opportunistic infections. Keratinocyte growth factor (KGF) stimulates TEC proliferation and, when given preconditioning, reduces TEC injury. Thymocytes and TECs express androgen receptors, ... | 10.1038/s41577-020-00457-z | This article shows that the combination of sex steroid ablation and KGF results in the preservation of thymic architecture, enhancement of T cell development and improvement of the T cell repertoire |
10.1084/jem.20131289 | 61,779,553 | Paradoxical to its importance for generating a diverse T cell repertoire, thymic function progressively declines throughout life. This process has been at least partially attributed to the effects of sex steroids, and their removal promotes enhanced thymopoiesis and recovery from immune injury. We show that one mechani... | 10.1038/s41577-020-00457-z | This study demonstrates that androgens suppress thymic function through the direct negative regulation of DLL4 expression |
10.1158/1078-0432.ccr-07-1784 | 100,989,457 | Abstract Purpose: To determine if temporarily blocking sex steroids prior to stem cell transplantation can increase thymus function and thus enhance the rate of T cell regeneration. Experimental Design: This was a pilot study of luteinizing hormone–releasing hormone agonist (LHRH-A) goserelin given 3 weeks prior to all... | 10.1038/s41577-020-00457-z | This is the first observation showing that pharmacological ablation of sex steroids enhances immune recovery in HCT recipients |
10.1126/science.1149726 | 104,306,238 | Upon intravenous transplantation, hematopoietic stem cells (HSCs) can home to specialized niches, yet most HSCs fail to engraft unless recipients are subjected to toxic preconditioning. We provide evidence that, aside from immune barriers, donor HSC engraftment is restricted by occupancy of appropriate niches by host H... | 10.1038/s41577-020-00457-z | Together with the articles by Czechowicz et al. (2019) and Palchaudhuri et al. (2016), this article documents the use of non-genotoxic conditioning approaches to deplete host haematopoietic cells in the BM niche and allow donor HSC engraftment |
10.1073/pnas.1707304114 | 125,127,481 | Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is t... | 10.1038/s41586-020-2798-3 | This study shows that coronavirus spike proteins can be stabilized by changing two amino acids in S2 to prolines |
10.1101/2020.08.13.20173161 | 83,393,970 | Abstract The development of vaccines against SARS-CoV-2 would be greatly facilitated by the identification of immunological correlates of protection in humans. However, to date, studies on protective immunity have only been performed in animal models and correlates of protection have not been established in humans. Her... | 10.1038/s41586-020-2798-3 | This study provides the first evidence that neutralizing antibodies may protect humans from SARS-CoV-2 infection |
10.1101/2020.07.31.20161216 | 83,231,541 | ABSTRACT BACKGROUND The top priority for the control of COVID-19 pandemic currently is the development of a vaccine. A phase 2 trial conducted to further evaluate the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine (CoronaVac). METHODS We conducted a randomized, double-blind, placebo-controlled trial to e... | 10.1038/s41586-020-2798-3 | This was the second study to show immunogenicity of an inactivated SARS-CoV-2 vaccine in humans |
10.1101/2020.08.17.20176651 | 123,161,660 | ABSTRACT Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally. Multiple vaccine candidates are under development, but no vaccine is currently available. Methods Healthy adults 18–55 a... | 10.1038/s41586-020-2798-3 | A key study comparing the immunogenicity of Pfizer’s mRNA-based RBD and spike vaccines in humans |
10.1084/jem.20150237 | 104,315,916 | Inflammation in the brain accompanies several high-impact neurological diseases including multiple sclerosis (MS), stroke, and Alzheimer’s disease. Neuroinflammation is sterile, as damage-associated molecular patterns rather than microbial pathogens elicit the response. The inflammasome, which leads to caspase-1 activa... | 10.1038/s41583-018-0055-7 | This paper shows that astrocytes also have functional NLRP3 and NLRC4 inflammasomes, and, interestingly, NLRC4 was detected in the brains of patients with multiple sclerosis |
10.1073/pnas.1610099113 | 41,498,748 | The aggregation of α-synuclein (aSyn) leading to the formation of Lewy bodies is the defining pathological hallmark of Parkinson’s disease (PD). Rare familial PD-associated mutations in aSyn render it aggregation-prone; however, PD patients carrying wild type (WT) aSyn also have aggregated aSyn in Lewy bodies. The mech... | 10.1038/s41583-018-0055-7 | These authors show that caspase 1 localizes with α-Syn Lewy bodies in patients with PD, and, importantly, caspase 1 directly cleaves α-Syn, resulting in fragments that can quickly aggregate and are toxic to neuronal cells |
10.1073/pnas.1002396107 | 125,207,597 | ALS is a fatal motor neuron disease of adult onset. Neuroinflammation contributes to ALS disease progression; however, the inflammatory trigger remains unclear. We report that ALS–linked mutant superoxide dismutase 1 (SOD1) activates caspase-1 and IL-1β in microglia. Cytoplasmic accumulation of mutant SOD1 was sensed b... | 10.1038/s41583-018-0055-7 | This study shows that mutant SOD can activate caspase 1 cleavage in microglia in an ASC-dependent manner, thus implicating the inflammasome in the progression of ALS |
10.1038/jcbfm.2009.46 | 83,184,336 | Traumatic brain injury elicits acute inflammation that in turn exacerbates primary brain damage. A crucial part of innate immunity in the immune privileged central nervous system involves production of proinflammatory cytokines mediated by inflammasome signaling. Here, we show that the nucleotide-binding, leucine-rich ... | 10.1038/s41583-018-0055-7 | This paper shows that TBI induces inflammasome activation in rats with cleavage of caspase 1 and IL-1β to their mature forms; however, this is attenuated by treatment with anti-ASC neutralizing antibodies, as is the contusion size induced by injury |
10.1002/chem.201404705 | 124,378,255 | Abstract A series of new, easily activated NHC–Pd II precatalysts featuring a trans ‐oriented morpholine ligand were prepared and evaluated for activity in carbon‐sulfur cross‐coupling chemistry. [(IPent)PdCl 2 (morpholine)] (IPent=1,3‐bis(2,6‐di(3‐pentyl)phenyl)imidazol‐2‐ylidene) was identified as the most active pre... | 10.1038/s41570-017-0025 | Catalytic improvements result simply by replacing pyridine with morpholine in the PEPPSI scaffold. |
10.1039/c6cs00159a | 103,696,480 | The review focuses on the development of hybrid organic–inorganic π conjugated, silane, siloxane and coordination polymers containing boron clusters, which have received considerable academic and technological interest due to the combination of the electronic, optical and thermal properties of traditional inorganic mat... | 10.1038/s41570-022-00400-x | A comprehensive review on the photophysical and redox properties of carboranes in photoluminescent and electrochemical applications |
10.1126/science.1232380 | 62,628,713 | Dysfunctions in frontostriatal brain circuits have been implicated in neuropsychiatric disorders, including those characterized by the presence of repetitive behaviors. We developed an optogenetic approach to block repetitive, compulsive behavior in a mouse model in which deletion of the synaptic scaffolding gene, Sapa... | 10.1038/s41572-019-0102-3 | This paper demonstrates the value of basic neuroscience research in shedding light on OCD |
10.1126/science.aao0958 | 104,357,719 | Although dynamics underlie many biological processes, our ability to robustly and accurately profile time-varying biological signals and regulatory programs remains limited. Here we describe a framework for storing temporal biological information directly in the genomes of a cell population. We developed a “biological ... | 10.1038/s41576-018-0052-8 | By utilizing a copy-number-inducible plasmid, the CRISPR–Cas integrase system is utilized to record and reconstruct temporally changing biological signals |
10.1126/science.aad8559 | 41,490,872 | Building a computing system in bacteria Finite state machines are logic circuits with a predetermined sequence of actions that are triggered depending on the starting conditions. They are used for a variety of devices and biological systems, from vending machines to neural circuits. Roquet et al. have taken a finite st... | 10.1038/s41576-018-0052-8 | Recombinase-based genetic circuits are formalized in a computer science state machine framework, enabling the design of synthetic circuits that discriminate the ordering of chemical inputs |
10.1126/science.1256272 | 125,187,535 | Cellular memory is crucial to many natural biological processes and sophisticated synthetic biology applications. Existing cellular memories rely on epigenetic switches or recombinases, which are limited in scalability and recording capacity. In this work, we use the DNA of living cell populations as genomic “tape reco... | 10.1038/s41576-018-0052-8 | A framework for writing genomic addresses utilizing ssDNA recombination is demonstrated, enabling recording of input signal intensity and duration and interfacing with host responses in E. coli |
10.1126/science.aap8992 | 123,443,168 | Writing a cell's history in its DNA Recording cellular events could advance our understanding of cellular history and responses to stimuli. The construction of intracellular memory devices, however, is challenging. Tang and Liu used Cas9 nucleases and base editors to record amplitude, duration, and order of stimuli as ... | 10.1038/s41576-018-0052-8 | The authors develop base-editing approaches for cellular recording applications in both E. coli and mammalian cells. |
10.1126/science.aaf7907 | 83,559,604 | INTRODUCTION The developmental path by which a fertilized egg gives rise to the cells of a multicellular organism is termed the cell lineage. In 1983, John Sulston and colleagues documented the invariant cell lineage of the roundworm Caenorhabditis elegans as determined by visual observation. However, tracing cell line... | 10.1038/s41576-018-0052-8 | Cas9-nuclease-based stochastic editing of target arrays is utilized to reconstruct the lineage of cells and zebrafish embryos |
10.1126/science.aag0511 | 123,896,345 | INTRODUCTION Technologies that enable the longitudinal tracking and recording of molecular events into genomic DNA would be useful for the detailed monitoring of cellular state in artificial and native contexts. Although previous systems have been used to memorize digital information such as the presence or absence of ... | 10.1038/s41576-018-0052-8 | The authors demonstrate recursive editing of single-guide RNA sequences, allowing for recording of signal intensity and duration in mammalian cells |
10.1126/science.aaf1175 | 62,304,845 | INTRODUCTION Although recent advances in DNA synthesis and sequencing technologies have made practical the writing and readout of arbitrary data in the form of synthetic DNA, still lacking are the robust tools necessary to generate a dynamic record of such information within the genomes of living cells. An in vivo syst... | 10.1038/s41576-018-0052-8 | In this work, the CRISPR–Cas integrase system is utilized to record the temporal ordering of oligonucleotide sequences electroporated into cell populations |
10.1557/mrs.2012.274 | 7,425,457 | Abstract | 10.1038/s41467-020-19858-8 | Also see: Crabtree, G. et al. From quanta to the continuum: opportunities for mesoscale science: a report from the Basic Energy Sciences Advisory Committee, U.S. DOE (2012) |
10.1111/all.13949 | 80,215,153 | Abstract Background Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high‐affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly cha... | 10.1038/s41572-022-00389-z | This international multicentre study characterizes for the first time the subpopulation of patients with autoimmune CSU diagnosed by triple positivity of the ASST, basophil tests and immunoassay. |
10.1111/all.14037 | 82,434,535 | Abstract Background and objectives Urticaria is a frequent skin condition, but reliable prevalence estimates from population studies particularly of the chronic form are scarce. The objective of this study was to systematically evaluate and summarize the prevalence of chronic urticaria by evaluating population‐based st... | 10.1038/s41572-022-00389-z | This systematic review and meta-analysis reports prevalence of CU on a global level and shows considerable regional differences. |
10.1111/all.15262 | 130,678,945 | Abstract Background Mast cells (MC) are powerful inflammatory immune sentinel cells that drive numerous allergic, inflammatory, and pruritic disorders when activated. MC‐targeted therapies are approved in several disorders, yet many patients have limited benefit suggesting the need for approaches that more broadly inhi... | 10.1038/s41572-022-00389-z | This publication describes systemic mast cell depletion associated with administration of an anti-KIT mAb that may represent a safe and novel approach to treat mast cell-driven disorders. |
10.1038/s41591-021-01537-w | 128,876,404 | Abstract Bruton’s tyrosine kinase (BTK) is crucial for FcεRI-mediated mast cell activation and essential for autoantibody production by B cells in chronic spontaneous urticaria (CSU). Fenebrutinib, an orally administered, potent, highly selective, reversible BTK inhibitor, may be effective in CSU. This double-blind, pl... | 10.1038/s41572-022-00389-z | The results of this study indicate that fenebrutinib, a BTK inhibitor, can be effective in reducing disease activity in patients with antihistamine-refractory CSU including patients with refractory type IIb autoimmunity. |
10.1111/cea.13616 | 103,191,069 | Abstract Background Chronic spontaneous urticaria (CSU) is considered an autoimmune disorder in 50% of cases at least, in which T‐ and mast cell mediators are considered to be the primary cause of symptoms. However, H 1 ‐antihistamines, cyclosporine A, and omalizumab fail to achieve complete symptom amelioration in up ... | 10.1038/s41572-022-00389-z | This report demonstrates efficacy of the anti-IL-17 mAb, secukinumab, in patients with antihistamine-resistant and omalizumab-resistant CSU, suggesting the role of IL-17 in disease pathogenesis. |
10.1111/all.12901 | 18,114,472 | Abstract Background GA² LEN , the Global Allergy and Asthma European Network, has recently launched a program for the development, interaction, and accreditation of centers of reference and excellence in special areas of allergy embedded in its overall quality management of allergy centers of excellence. The first area... | 10.1038/s41572-022-00389-z | This publication describes the aims, the requirements and deliverables, the application process and the audit and accreditation protocol for Urticaria Centers of Reference and Excellence |
10.1111/jdv.16947 | 79,807,154 | Abstract Background Chronic urticaria (CU) is a common disease, characterized by the recurrent appearance of wheals, angioedema or both for more than 6 weeks. Its underlying biology is not well understood, and many patients do not obtain sufficient relief from recommended treatments. Patient registries are rapidly grow... | 10.1038/s41572-022-00389-z | This report describes the rationale, methods and implementation of the CURE |
10.1073/pnas.1908626116 | 38,296,016 | Pancreatic ductal adenocarcinoma (PDAC) has prominent extracellular matrix (ECM) that compromises treatments yet cannot be nonselectively disrupted without adverse consequences. ECM of PDAC, despite the recognition of its importance, has not been comprehensively studied in patients. In this study, we used quantitative ... | 10.1038/s41568-020-00329-7 | Study using proteomics on human-in-mouse tumour xenografts to dissect the contribution of tumour versus non-tumour cells to matrix deposition |
10.1126/science.aao4227 | 104,265,087 | Cancer cells from a primary tumor can disseminate to other tissues, remaining dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to awaken, resume proliferating, and develop into metastases. Studying mouse models, we found that sustained lung inflammation c... | 10.1038/s41568-020-00329-7 | Study that sheds new, unexpected light on the mechanisms involved in neutrophil-mediated tumour promotion through remodelling of the extracellular matrix |
10.1038/s41568-019-0238-1 | 20,879,618 | Abstract Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimi... | 10.1038/s41568-020-00329-7 | A consensus framework for the identification and study of CAFs and their roles in cancer |
10.1126/scitranslmed.aai8504 | 104,197,455 | Fine-tuned manipulation of tumor tension and vasculature enhances response to chemotherapy and impairs metastatic spread in pancreatic cancer. | 10.1038/s41568-020-00329-7 | Study demonstrating how inhibition of ROCK signalling in tumours disrupts matrix remodelling, leading to decreased metastasis and increased response to therapy in pancreatic cancer models. |
10.1038/s41467-019-10968-6 | 20,344,068 | Abstract Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote and restrain disease progression. Here, we interrogate how cancer cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence of a p53-driven hierarchy, where ca... | 10.1038/s41568-020-00329-7 | Study in pancreatic cancer dissecting how the genotype of cancer cells shapes their secretomes to differentially reprogramme local CAF populations, leading to remodelling of the matrix, creating proinvasive and chemoprotective microenvironments |
10.1146/annurev-environ-021913-153558 | 78,993,095 | Energy efficiency policies are pursued as a way to provide affordable and sustainable energy services. Efficiency measures that reduce energy service costs will free up resources that can be spent in the form of increased consumption—either of that same good or service or of other goods and services that require energy... | 10.1038/s41560-021-00889-4 | A Review Article on the various definitions of rebound, the research gaps in the literature and the importance of scope in estimating rebound |
10.1007/s12053-019-09823-w | 99,984,669 | Abstract The direct rebound effect for private car transport was estimated by following a large sample of Swedish households (28,876) that acquired a new car in 2009. For some households, this resulted in an improvement in fuel efficiency, whereas others acquired a less or similarly fuel efficient car. The households’ ... | 10.1038/s41560-021-00889-4 | This empirical study shows that when drivers switch to more efficient cars that are green-labelled, direct rebound is null |
10.1038/s41467-019-12457-2 | 82,975,810 | Abstract No consensus exists regarding which are the most effective mechanisms to promote household action on climate change. We present a meta-analysis of randomised controlled trials comprising 3,092,678 observations, which estimates the effects of behavioural interventions holding other factors constant. Here we sho... | 10.1038/s41560-021-00889-4 | This recent meta-analysis finds that the size of emissions reduction of various behavioural interventions is not as big as previously thought |
10.1177/1747493021990945 | 38,187,931 | Background The burden of stroke is high in sub-Saharan Africa; however, few data are available on long-term mortality. Objective To estimate over one-month stroke case fatality in sub-Saharan Africa. Methods A systematic review and meta-analysis were performed according to meta-analysis of observational studies in epid... | 10.1038/s41582-021-00542-4 | This is a very recent systematic review of stroke case fatality in sub-Saharan Africa that highlights the heterogeneity of stroke outcomes across Africa |
10.1159/000306058 | 45,417,648 | Stroke is a major global health problem. It is the third leading cause of death and the leading cause of adult disability. INTERHEART, a global case-control study of acute myocardial infarction in 52 countries (29,972 participants), identified nine modifiable risk factors that accounted for >90% of population-attrib... | 10.1038/s41582-021-00542-4 | The INTERSTROKE study remains the reference study in understanding the risk factors for stroke across the globe. Regional variations in the differential effect sizes of stroke risk factors are clearly demonstrated |
10.1038/s41525-019-0111-x | 40,365,580 | Abstract The lack of representation of diverse ancestral backgrounds in genomic research is well-known, and the resultant scientific and ethical limitations are becoming increasingly appreciated. The paucity of data on individuals with African ancestry is especially noteworthy as Africa is the birthplace of modern huma... | 10.1038/s41582-021-00542-4 | This is an important opinion piece that makes a very strong case for diversity, inclusion and better representation of populations of African ancestry in genomics studies |
10.1177/2396987318808719 | 18,900,108 | Two previous pan-European consensus meetings, the 1995 and 2006 Helsingborg meetings, were convened to review the scientific evidence and the state of current services to identify priorities for research and development and to set targets for the development of stroke care for the decade to follow. Adhering to the same... | 10.1038/s41582-021-00542-4 | This is a vital report on the strategic action plan for enhancing stroke care in Europe |
10.1177/1747493017711949 | 9,384,204 | Background The rate of alteplase (tPA) thrombolysis utilization in acute stroke in Egypt is <1%. We report on the causes of this low rate of reperfusion therapies and take corrective action to improve it. Methods Two prospective observational studies were conducted at Ain Shams University hospitals. The first includ... | 10.1038/s41582-021-00542-4 | This study reports a substantial increase in the use of reperfusion therapies for acute ischaemic stroke in Egypt over a relatively short period |
10.1177/1747493019897871 | 83,103,184 | Africa is the world’s most genetically diverse, second largest, and second most populous continent, with over one billion people distributed across 54 countries. With a 23% lifetime risk of stroke, Africa has some of the highest rates of stroke worldwide and many occur in the prime of life with huge economic losses and... | 10.1038/s41582-021-00542-4 | This paper describes the conceptual framework underscoring the establishment of the African Stroke Organization, a prime stroke leadership effort in Africa |
10.1126/science.1131914 | 62,151,156 | Nucleophilic, anionic boryl compounds are long-sought but elusive species. We report that reductive cleavage of the boron-bromine bond in N,N ′-bis(2,6-diisopropylphenyl)-2-bromo-2,3-dihydro-1 H -1,3,2-diazaborole by lithium naphthalenide afforded the corresponding boryllithium, which is isoelectronic with an N -hetero... | 10.1038/s41570-021-00276-3 | The first report of an anionic boryl compound isoelectronic with carbenes |
10.1002/anie.201607537 | 62,617,238 | Abstract The synthesis of N ‐heterocyclic carbene (NHC)–cyclic (alkyl)(amino) carbene (CAAC) heterodimers is presented. As the free carbenes do not react together in solution, the synthetic approach involves the addition of a free NHC to a cyclic iminium salt, which results in the formation of the protonated heterodime... | 10.1038/s41570-021-00276-3 | Evidence that triaminoolefins have similar redox and photophysical properties to tetrathiafulvalene |
10.1126/science.aah4345 | 60,880,165 | Adding a twist for enhanced performance The efficiency of organic light-emitting diodes (OLEDs) is fundamentally governed by the ratio of emissive singlet to dark triplet excitons that are formed from spin-polarized electron and hole currents within the material. Typically, this has set an upper limit of 25% internal q... | 10.1038/s41570-021-00276-3 | Seminal report on the application of carbene–metal–amido complexes in organic light-emitting diodes |
10.1126/scitranslmed.aal3694 | 125,256,760 | Development of NASH fibrosis is accompanied by accumulation of hepatic eosinophils and driven by TGF-β and profibrotic type 2 inflammation. | 10.1038/s41586-020-2938-9 | This study identified opposing roles for type 2 immunity in metabolic syndrome and liver fibrosis in an experimental model of NASH |
10.1126/science.1181369 | 41,754,439 | Chromosomal Mapping The conformation of the genome in the nucleus and contacts between both proximal and distal loci influence gene expression. In order to map genomic contacts, Lieberman-Aiden et al. (p. 289 , see the cover) developed a technique to allow the detection of all interactions between genomic loci in the e... | 10.1038/s41576-019-0128-0 | This work established Hi-C as a method to capture chromosomal interactions genome-wide |
10.1126/science.aau1783 | 125,282,902 | The spatial organization of chromatin is pivotal for regulating genome functions. We report an imaging method for tracing chromatin organization with kilobase- and nanometer-scale resolution, unveiling chromatin conformation across topologically associating domains (TADs) in thousands of individual cells. Our imaging d... | 10.1038/s41576-019-0128-0 | In this study, super-resolution microscopy of the chromatin structure uncovers TAD-like domains in single cells that persist in the absence of cohesin |
10.1126/science.aao3136 | 19,061,203 | Tracking regulatory DNA in action Cis-regulatory DNA elements such as enhancers and promoters are critical for transcription regulation. Little is known about the relationship between these elements' transcriptional activity and their mobility within the nucleus in living cells. Gu et al. developed a strategy to delive... | 10.1038/s41576-019-0128-0 | This study uses live imaging of regulatory elements to reveal a transcription-dependent increased mobility of both enhancers and promoters upon activation |
10.1111/bph.14710 | 100,515,663 | Hypothalamic–pituitary–adrenal (HPA) axis dysfunction has long been implicated in the pathophysiology of depression, and HPA axis‐based compounds have served as potential new therapeutic targets, but with no success. This review details sex differences from animal and human studies in the function of HPA axis elements ... | 10.1038/s41583-021-00513-0 | This review synthesizes details of how antidepressants developed only in male rodents fail clinical testing when females are included in the trials |
10.1073/pnas.2011890117 | 62,462,396 | Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different p... | 10.1038/s41583-021-00513-0 | This paper demonstrates that oxytocin synthesis within the BNST is necessary for stress-induced disruptions in social approach and vigilance |
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