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10.4049/jimmunol.174.4.1783 | 20,661,928 | Abstract CD4+CD25+ regulatory T cells (Treg) are potent immunosuppressive cells that are pivotal in the regulation of peripheral tolerance. In this report, we identify granzyme B (GZ-B) as one of the key components of Treg-mediated suppression. Induction of regulatory activity is correlated with the up-regulation of GZ... | 10.1038/s41577-019-0232-6 | This paper shows that T reg cells can exert cytolytic activity in a granzyme B-dependent manner. |
10.1126/science.aar3246 | 4,860,145 | Engineering cytokine-receptor pairs Interleukin-2 (IL-2) is an important cytokine that helps T cells destroy tumors and virus-infected cells. IL-2 has great therapeutic promise but is limited by toxic side effects and its capacity to both activate and repress immune responses. Sockolosky et al. set out to improve IL-2–... | 10.1038/s41577-019-0232-6 | In this study, in order to counteract the pleiotropic effect of IL-2, the authors engineer IL-2 cytokine–receptor orthogonal pairs that can selectively interact with one another, providing a discriminating IL-2 signal to engineered T cells expressing the orthogonal IL-2R when in the presence of orthogonal IL-2 cytokine... |
10.1084/jem.20060772 | 62,152,027 | Regulatory T (T reg) cells are critical regulators of immune tolerance. Most T reg cells are defined based on expression of CD4, CD25, and the transcription factor, FoxP3. However, these markers have proven problematic for uniquely defining this specialized T cell subset in humans. We found that the IL-7 receptor (CD12... | 10.1038/s41577-019-0232-6 | This paper identifies CD127 as a biomarker that discriminates human T reg cells (CD127 −/low ) from CD4 + conventional T cells (CD127 + ) in the peripheral blood and that, when combined with the surface marker CD25, enables the enrichment of T reg cells with high purity. |
10.1073/pnas.0812721106 | 104,336,476 | The severity of damaging human-induced climate change depends not only on the magnitude of the change but also on the potential for irreversibility. This paper shows that the climate change that takes place due to increases in carbon dioxide concentration is largely irreversible for 1,000 years after emissions stop. Fo... | 10.1038/s41558-022-01456-9 | This paper demonstrates that global climate change due to CO 2 emissions might be largely irreversible. |
10.2337/db20-1111 | 35,586,375 | Excess nutritional supply to the growing fetus, resulting from maternal diabetes and obesity, is associated with increased risks of fetal maldevelopment and adverse metabolic conditions in postnatal life. The placenta, interposed between mother and fetus, serves as the gateway between the two circulations and is usuall... | 10.1038/s41574-022-00717-z | Introduces the concept of limitations to placental adaptation as a cause of adverse pregnancy outcomes |
10.1113/jp271099 | 62,420,230 | Abstract How the fetus withstands an environment of reduced oxygenation during life in the womb has been a vibrant area of research since this field was introduced by Joseph Barcroft, a century ago. Studies spanning five decades have since used the chronically instrumented fetal sheep preparation to investigate the fet... | 10.1038/s41574-022-00717-z | An excellent review of the physiological responses to fetal hypoxia |
10.1002/uog.88 | 103,111,960 | Abstract Objective Type‐I diabetic pregnancies are associated with congenital cardiac malformations, fetal cardiomyopathy, venous thrombosis and altered placental vascularization, even with tight maternal glucose control. The aim of this study was to investigate if, with good glucose control achieved with continuous su... | 10.1038/s41574-022-00717-z | Finds significant differences in the fetal circulation in pregnancies with T1DM and those without T1DM and suggests the existence of compensatory mechanisms |
10.1038/s41467-022-29801-8 | 127,655,015 | Abstract Chronological age is a risk factor for SARS-CoV-2 infection and severe COVID-19. Previous findings indicate that epigenetic age could be altered in viral infection. However, the epigenetic aging in COVID-19 has not been well studied. In this study, DNA methylation of the blood samples from 232 healthy individu... | 10.1038/s41556-023-01097-w | This paper reports epigenetic aging in patients with severe COVID-19. |
10.1126/science.aau6509 | 41,699,672 | Melanomas originating from mucosal surfaces have low mutation burden, genomic instability, and poor prognosis. To identify potential driver genes, we sequenced hundreds of cancer-related genes in 43 human mucosal melanomas, cataloging point mutations, amplifications, and deletions. The SPRED1 gene, which encodes a nega... | 10.1038/s41568-020-0252-3 | This article shows rapid generation of genetic avatars in zebrafish using combinatorial mosaic transgenesis |
10.1073/pnas.1618389114 | 62,412,249 | Cancer is as unique as the person fighting it. With the exception of a few biomarker-driven therapies, patients go through rounds of trial-and-error approaches to find the best treatment. Using patient-derived cell lines, we show that zebrafish larvae xenotransplants constitute a fast and highly sensitive in vivo model... | 10.1038/s41568-020-0252-3 | This study conducts phenotypic drug response testing and migration scoring of PDXs in zebrafish larvae |
10.1126/science.1080280 | 62,413,057 | The zebrafish is an attractive model organism for studying cancer development because of its genetic accessibility. Here we describe the induction of clonally derived T cell acute lymphoblastic leukemia in transgenic zebrafish expressing mouse c- myc under control of the zebrafish Rag2 promoter. Visualization of leukem... | 10.1038/s41568-020-0252-3 | This article reports the first transgenic cancer model in zebrafish |
10.1101/297234 | 61,838,958 | Abstract Transgenic animals are invaluable for modeling cancer genomics, but often require complex crosses of multiple germline alleles to obtain the desired combinations. Zebrafish models have advantages in that transgenes can be rapidly tested by mosaic expression, but these typically lack spatial and temporal contro... | 10.1038/s41568-020-0252-3 | This article shows mosaic transgenesis in adult zebrafish through electroporation of plasmid DNA |
10.1073/pnas.1705301114 | 38,310,504 | Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized ... | 10.1038/s41568-020-0252-3 | This article reports engineering of NSG mice towards humanized models and more robust PDX support |
10.1242/dmm.024166 | 38,322,334 | Zebrafish are a major model for chemical genetics, and most studies use embryos to find small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules, and relied on water-born exposure or injection techniques. Challenges in drug delivery-rela... | 10.1038/s41568-020-0252-3 | This study administers a drug in adult zebrafish through intraperitoneal injection and oral gavage |
10.3390/cancers12030677 | 85,643,018 | Animal “avatars” and co-clinical trials are being developed for possible use in personalized medicine in oncology. In a co-clinical trial, the cancer cells of the patient’s tumor are xenotransplanted into the animal avatar for drug efficacy studies, and the data collected in the animal trial are used to plan the best d... | 10.1038/s41568-020-0252-3 | This article reports preliminary results of zebrafish co-clinical trial NCT03668418 |
10.1002/wcc.678 | 102,918,859 | Abstract The transition to a low‐carbon economy will entail a large‐scale structural change. Some industries will have to expand their relative economic weight, while other industries, especially those directly linked to fossil fuel production and consumption, will have to decline. Such a systemic shift may have major ... | 10.1038/s41558-022-01373-x | This article reviews and categorizes the various channels (such as stranded assets) through which climate change mitigation can impact the financial system |
10.1146/annurev-pathol-052016-100332 | 101,627,039 | Immunodeficient mice engrafted with functional human cells and tissues, that is, humanized mice, have become increasingly important as small, preclinical animal models for the study of human diseases. Since the description of immunodeficient mice bearing mutations in the IL2 receptor common gamma chain (IL2rg null ) in... | 10.1038/s41592-022-01584-2 | This Review article presents an overview of humanized mouse models and their use in clinical research. |
10.1126/science.1110340 | 19,686,740 | Ubiquitination controls a broad range of cellular functions. The last step of the ubiquitination pathway is regulated by enzyme type 3 (E3) ubiquitin ligases. E3 enzymes are responsible for substrate specificity and catalyze the formation of an isopeptide bond between a lysine residue of the substrate (or the N terminu... | 10.1038/s41589-022-01088-2 | This manuscript describes cysteine ubiquitination carried out by a viral E3 ligase and represents the first report of non-lysine ubiquitination |
10.1083/jcb.200908036 | 60,451,568 | Ubiquitin (Ub) modification of proteins plays a prominent role in the regulation of multiple cell processes, including endoplasmic reticulum–associated degradation (ERAD). Until recently, ubiquitination of substrates was thought to occur only via isopeptide bonds, typically to lysine residues. Several recent studies su... | 10.1038/s41589-022-01088-2 | This paper reveals that the endoplasmic reticulum-associated E2 conjugating enzyme UBE2J2 preferentially ubiquitinates serine and threonine residues thereby establishing a physiological role for non-lysine ubiquitination |
10.1073/pnas.1905873116 | 82,331,641 | The linear ubiquitin assembly complex (LUBAC) comprises 3 components: HOIP, HOIL-1, and Sharpin, of which HOIP and HOIL-1 are both members of the RBR subfamily of E3 ubiquitin ligases. HOIP catalyses the formation of Met1-linked ubiquitin oligomers (also called linear ubiquitin), but the function of the E3 ligase activ... | 10.1038/s41589-022-01088-2 | This report reveals that the RBR E3 ligase HOIL-1 ubiquitinates components of the Myddosome signalling complex establishing a role for non-lysine ubiquitination in immune system signalling |
10.1073/pnas.2006947118 | 124,115,522 | The reversibility of ubiquitination by the action of deubiquitinating enzymes (DUBs) serves as an important regulatory layer within the ubiquitin system. Approximately 100 DUBs are encoded by the human genome, and many have been implicated with pathologies, including neurodegeneration and cancer. Non-lysine ubiquitinat... | 10.1038/s41589-022-01088-2 | The first comprehensive assessment of whether DUBs can remove ubiquitin from non-lysine amino acids and reveals that the Machado-Joseph Disease (MJD) DUB class have highly selective esterase activity towards model substrates |
10.1038/s41467-021-22295-w | 20,428,834 | Abstract Prime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor DNA as a template. PEs facilitate nucleotide substitutions or local insertions or deletions within the genome based on the template sequence encoded within the prime editing guide RNA (pegRNA). Howev... | 10.1038/s41578-021-00396-8 | This paper describes the optimization of genome editors with nuclear localization signals to improve genome editing efficiency in vivo |
10.1073/pnas.2003034117 | 101,561,666 | Innate immune cells destroy pathogens within a transient organelle called the phagosome. When pathogen-associated molecular patterns (PAMPs) displayed on the pathogen are recognized by Toll-like receptors (TLRs) on the host cell, it activates inducible nitric oxide synthase (NOS2) which instantly fills the phagosome wi... | 10.1038/s41578-021-00396-8 | This paper shows how DNA nanodevices are targeted with organelle-level precision specifically in microglia of live zebrafish and that the DNA sequence can be modified to either trigger or evade the immune response |
10.1002/mds.27415 | 80,954,053 | ABSTRACT The recessive cerebellar ataxias are a large group of degenerative and metabolic disorders, the diagnostic management of which is difficult because of the enormous clinical and genetic heterogeneity. Because of several limitations, the current classification systems provide insufficient guidance for clinicians... | 10.1038/s41582-022-00634-9 | This article presents the revised nomenclature of recessive cerebellar ataxias, in which an ATX prefix is followed by the gene name. |
10.1002/acn3.332 | 82,323,502 | Abstract Objective Friedreich ataxia ( FRDA ) is a progressive neurodegenerative disorder of adults and children. This study analyzed neurological outcomes and changes to identify predictors of progression and generate power calculations for clinical trials. Methods Eight hundred and twelve subjects in a natural histor... | 10.1038/s41582-022-00634-9 | This article presents the 5-year longitudinal data in the FA-COMS study, a large international collaborative study on the natural history of Friedreich ataxia. |
10.1002/ana.26200 | 131,922,422 | Objective Friedreich ataxia (FRDA) is an inherited neurological disease defined by progressive movement incoordination. We undertook a comprehensive characterization of the spatial profile and progressive evolution of structural brain abnormalities in people with FRDA. Methods A coordinated international analysis of re... | 10.1038/s41582-022-00634-9 | Results of a large-scale international collaboration on imaging findings in Friedreich ataxia, covering the whole spectrum of findings according to age at onset and disease duration. |
10.1093/brain/awz418 | 38,308,801 | Abstract Ataxia, causing imbalance, dizziness and falls, is a leading cause of neurological disability. We have recently identified a biallelic intronic AAGGG repeat expansion in replication factor complex subunit 1 (RFC1) as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and a major... | 10.1038/s41582-022-00634-9 | This article presents the largest series of patients with biallelic RFC1 mutations published so far, with detailed clinical phenotyping. |
10.1093/brain/awab072 | 123,035,398 | Abstract After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is id... | 10.1038/s41582-022-00634-9 | This article shows the phenotypic variability of biallelic RFC1 mutations and details the sensory involvement. |
10.1126/science.1192912 | 104,412,367 | Stress, DNA Damage, and ATM The protein kinase ATM (ataxia-telangiectasia mutated) is a key component of the signaling pathway through which cells are protected from DNA damage. ATM becomes activated within a protein complex at sites of double-stranded breaks in DNA. ATM is also activated in response to increased produ... | 10.1038/s41582-022-00634-9 | A landmark paper on the role of ATM in regulating oxidative stress. |
10.1002/ana.25934 | 20,766,782 | Objective Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with ... | 10.1038/s41582-022-00634-9 | This phase II study produced promising results with respect to the efficacy of omaveloxolone, a molecule that targets oxidative stress, in patients with Friedreich ataxia. |
10.1111/ene.12341 | 80,927,952 | Background and objectives The ataxias are a challenging group of neurological diseases due the aetiological heterogeneity and the complexity of the genetic subtypes. This guideline focuses on the heredodegenerative ataxias. The aim is to provide a peer‐reviewed evidence‐based guideline for clinical neurologists and oth... | 10.1038/s41582-022-00634-9 | An evidence-based guideline on the diagnosis and management of chronic ataxias in adults. |
10.1101/2021.11.08.21265944 | 133,936,557 | Abstract The Coronavirus Disease 2019 (COVID-19) pandemic continues to pose a major public health threat especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity we formed the COVID19 Host Genetics Initiative. Here we present GWA... | 10.1038/s41576-022-00478-5 | The largest GWAS of COVID-19 infection susceptibility and severity. The consortium regularly release results online ( ) and describes them via publication; see also reference 51, COVID-19 Host Genetics Initiative & Ganna, A. (2021) |
10.1038/s41467-020-19478-2 | 20,794,599 | Abstract Numerous observational studies have attempted to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes. Studies have used datasets sampled from patients admitted to hospital, people tested for active infection, or people who volunteered to participate. Here, we highlight the challen... | 10.1038/s41576-022-00478-5 | This study describes how collider bias challenges the interpretation of many COVID-19 observational studies |
10.1126/science.abj3624 | 134,543,689 | The bat connection The heterogeneity of COVID-19 makes it challenging to predict the course of infection in an individual. Upon virus infection, interferons (IFNs) generate the initial signals for cellular defenses. Knowing that defects in IFN signaling are associated with more severe COVID-19, Wickenhagen et al . used... | 10.1038/s41576-022-00478-5 | This study links a prenylated OAS1 haplotype, which is common among humans and also present in horseshoe bats, with COVID severity |
10.1038/s41588-021-00996-8 | 133,239,983 | Abstract The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1 , which occurs in pe... | 10.1038/s41576-022-00478-5 | This paper identifies the causal variant for the OAS1 locus associated with COVID-19 severity |
10.1126/science.abn1934 | 132,011,059 | In skeletal muscle, nebulin stabilizes and regulates the length of thin filaments, but the underlying mechanism remains nebulous. In this work, we used cryo–electron tomography and subtomogram averaging to reveal structures of native nebulin bound to thin filaments within intact sarcomeres. This in situ reconstruction ... | 10.1038/s41592-023-01783-5 | High-resolution in situ structures obtained on FIB lamellae, showing structural differences with structures obtained on isolated proteins |
10.1126/science.abd3629 | 62,149,603 | Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and messenger RNAs can travel from these sealed replication compartments to... | 10.1038/s41592-023-01783-5 | Timely study on the structural characterisation of a molecular pore formed by coronaviruses, which were not previously structurally characterized |
10.7554/elife.45919 | 20,348,617 | Cryo-electron tomography (cryo-ET) is emerging as a revolutionary method for resolving the structure of macromolecular complexes in situ. However, sample preparation for in situ Cryo-ET is labour-intensive and can require both cryo-lamella preparation through cryo-focused ion beam (FIB) milling and correlative light mi... | 10.1038/s41592-023-01783-5 | Integration of a fluorescence microscope in a cryo-FIB/SEM microscope for CLEM |
10.1038/s41598-018-37728-8 | 20,350,308 | Abstract Sample fixation by vitrification is critical for the optimal structural preservation of biomolecules and subsequent high-resolution imaging by cryo-correlative light and electron microscopy (cryoCLEM). There is a large resolution gap between cryo fluorescence microscopy (cryoFLM), ~400-nm, and the sub-nanometr... | 10.1038/s41592-023-01783-5 | Study demonstrating localization-based super-resolution cryo-fluorescence microscopy on mammalian cells and characterization of the light intensities that can be used without devitrifying samples |
10.1038/s41467-021-24721-5 | 135,269,482 | Abstract Septins are cytoskeletal proteins that assemble into hetero-oligomeric complexes and sense micron-scale membrane curvature. During infection with Shigella flexneri , an invasive enteropathogen, septins restrict actin tail formation by entrapping bacteria in cage-like structures. Here, we reconstitute septin ca... | 10.1038/s41467-021-26641-w | Describes an in vitro reconstitution system for bacterial entrapment based on purified recombinant septin complexes, highlighting the great potential of ‘bottom-up’ cellular microbiology |
10.1126/science.aat9689 | 80,305,558 | Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis , remains the world’s deadliest infectious disease. Sterilizing chemotherapy requires at least 6 months of multidrug therapy. Difficulty visualizing the subcellular localization of antibiotics in infected host cells means that it is unclear w... | 10.1038/s41467-021-26641-w | Shows that host cell lipid droplets can act as a reservoir for the lipophilic antitubercular antibiotic bedaquilin, highlighting the importance of pharmacokinetics in antibiotic therapy |
10.1038/s41467-020-17094-8 | 122,544,946 | Abstract Studying emerging or neglected pathogens is often challenging due to insufficient information and absence of genetic tools. Dual RNA-seq provides insights into host-pathogen interactions, and is particularly informative for intracellular organisms. Here we apply dual RNA-seq to Orientia tsutsugamushi (Ot), an ... | 10.1038/s41467-021-26641-w | Shows how dual RNA-seq can illuminate the intracellular lifestyle of a poorly characterized and genetically intractable bacterial pathogen |
10.1002/acr.23887 | 81,132,043 | Objective The California Lupus Surveillance Project ( CLSP ) is a population‐based registry of individuals with systemic lupus erythematosus ( SLE ) residing in San Francisco County, California from 2007 to 2009, with a special focus on Asian/Pacific Islander and Hispanic patients. We used retrospective CLSP data to an... | 10.1038/s41572-019-0141-9 | This epidemiological study demonstrates that black, Asian/Pacific Islander and Hispanic individuals are at increased risk of developing severe LN following SLE diagnosis |
10.1126/sciimmunol.aap8855 | 125,270,725 | Biallelic TLR7 expression in immune cells may contribute to increased autoimmune disease risk in women. | 10.1038/s41572-019-0141-9 | This landmark article provides evidence that escape of X chromosome genes from X inactivation can lead to immune activation, and this may explain, in part, the higher prevalence of autoimmunity in females |
10.1084/jem.20151876 | 83,286,263 | Autoantibodies against nucleic acids and excessive type I interferon (IFN) are hallmarks of human systemic lupus erythematosus (SLE). We previously reported that SLE neutrophils exposed to TLR7 agonist autoantibodies release interferogenic DNA, which we now demonstrate to be of mitochondrial origin. We further show tha... | 10.1038/s41572-019-0141-9 | This article ties together the pathogenetic roles of oxidized mitochondrial DNA and type I interferon in SLE |
10.1002/art.40452 | 17,577,155 | Cells of the innate immune system are rigged with sensors that detect nucleic acids derived from microbes, especially viruses. It has become clear that these same sensors that respond to nucleic acids derived from damaged cells or defective intracellular processing are implicated in triggering diseases such as lupus an... | 10.1038/s41572-019-0141-9 | This review provides a critical discussion of how aberrant nucleic acid sensing may relate to the pathogenesis of SLE |
10.1002/art.40724 | 62,514,389 | Objective End points currently used in lupus nephritis (LN) clinical trials lack uniformity and questionably reflect long‐term kidney survival. This study was undertaken to identify short‐term end points that predict long‐term kidney outcomes for use in clinical trials. Methods A database of 944 patients with LN was as... | 10.1038/s41572-019-0141-9 | An analysis of multiple trial data sets presenting a proteinuria threshold that is associated with fortunate long-term outcomes |
10.1002/art.38220 | 83,020,353 | Objective Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that exhibits familial aggregation and may progress to end‐stage renal disease (ESRD). LN is more prevalent among African Americans than among European Americans. This study was undertaken to investigate the hypothesis that t... | 10.1038/s41572-019-0141-9 | A study that establishes the diagnostic value of APOL1 variants in predicting the progression of CKD in patients with LN |
10.1177/0961203308100481 | 15,292,258 | Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disorder, which often involves referral to multiple medical specialists. Lupus nephritis (LN) occurs in ~35% of adults with SLE and predicts poor survival. There is currently no consensus on how to manage patients with SLE or LN across specialties ... | 10.1038/s41572-019-0141-9 | This article provides guidance regarding LN classification and definitions of induction, response, flare and maintenance |
10.1136/annrheumdis-2012-201940 | 62,305,963 | Objectives To develop recommendations for the management of adult and paediatric lupus nephritis (LN). Methods The available evidence was systematically reviewed using the PubMed database. A modified Delphi method was used to compile questions, elicit expert opinions and reach consensus. Results Immunosuppressive treat... | 10.1038/s41572-019-0141-9 | This article provides EULAR/ERA–EDTA treatment recommendations for the management of LN. An update is in preparation |
10.1002/art.10461 | 83,048,608 | Abstract Objective Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low‐dose IV CYC prescribed a... | 10.1038/s41572-019-0141-9 | A randomized clinical trial that shows efficacy and safety of low-dose intravenous cyclophosphamide therapy (ELNT regimen) in the treatment of LN |
10.1002/art.34359 | 20,598,396 | Abstract Objective To evaluate the efficacy and safety of rituximab in a randomized, double‐blind, placebo‐controlled phase III trial in patients with lupus nephritis treated concomitantly with mycophenolate mofetil (MMF) and corticosteroids. Methods Patients (n = 144) with class III or class IV lupus nephritis were ra... | 10.1038/s41572-019-0141-9 | A randomized clinical trial comparing safety and efficacy of rituximab added to the standard-of-care immunosuppressive therapy in the treatment of LN. The study did not meet the primary end points |
10.1136/annrheumdis-2017-211641 | 19,358,341 | Objectives Exploring the associations between disease activity and medications with offspring birth weight, pre-eclampsia and preterm birth in systemic lupus erythematosus (SLE). Methods Data from the Medical Birth Registry of Norway (MBRN) were linked with data from RevNatus, a nationwide observational register recrui... | 10.1038/s41572-019-0141-9 | This study compares the frequency of serious adverse outcomes in pregnancy in patients with active and inactive SLE with the general population in a national registry and emphasizes that active SLE enhances the risk of these outcomes |
10.1177/0961203316646459 | 6,343,733 | Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which can affect any organ in the body, reducing patients' health-related quality of life (HR-QOL). Psychosocial research on SLE is quite recent and is mostly based on qualitative and cross-sectional evidence. Some studies suggest that a pro... | 10.1038/s41572-019-0141-9 | This study indicates that the HRQOL of patients with SLE is influenced by self-efficacy in the management of the disease and problematic support |
10.1177/0961203317717082 | 115,274,400 | Background Patient-reported outcomes in lupus nephritis (LN) are not well studied. Studies with disease-targeted PRO tool in LN do not exist. Herein, we describe quality of life (QOL: HRQOL & non-HRQOL) among LN patients using LupusPRO. Methods International, cross-sectional data from 1259 patients with systemic lu... | 10.1038/s41572-019-0141-9 | These international, cross-sectional data from a large cohort of patients with SLE demonstrate that patients with active LN have worse quality of life than those with inactive LN |
10.1126/scitranslmed.aat5580 | 103,529,525 | Considerable progress has been made in testing stem cell–derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional vali... | 10.1038/s41592-022-01702-0 | This article reports a detailed protocol to differentiate RPE cells and pericytes from iPSCs. |
10.1126/science.aar8174 | 20,419,195 | The majority of organellar proteins are translated on cytosolic ribosomes and must be sorted correctly to function. Targeting routes have been identified for organelles such as peroxisomes and the endoplasmic reticulum (ER). However, little is known about the initial steps of targeting of mitochondrial proteins. In thi... | 10.1038/s41580-020-00300-2 | This study discovers that the surface of the ER forms a platform to bind precursors of mitochondrial membrane proteins to facilitate their transport to mitochondria |
10.1126/science.aan4146 | 41,654,541 | The mitoCPR unclogs mitochondria The import of proteins into mitochondria is essential for cell viability. How cells respond when mitochondrial protein import is impaired is poorly understood. Weidberg and Amon showed that upon mitochondrial import stress, yeast cells mounted a response known as the mitoCPR. mitoCPR wa... | 10.1038/s41580-020-00300-2 | This article identifies the mitoCPR pathway, which removes translocation-arrested precursor proteins from the TOM complex |
10.1126/science.1223560 | 125,265,638 | Initiating Mitochondrial Repair The mitochondrial unfolded protein response (UPRmt) mediates the up-regulation of nuclear encoded mitochondrial chaperone genes in response to mitochondrial dysfunction. How mitochondrial dysfunction is communicated to the nucleus is unclear, but requires the transcription factor, ATFS-1... | 10.1038/s41580-020-00300-2 | This study identifies that impaired protein import into mitochondria in C. elegans leads to nuclear localization of ATFS-1, where it induces transcription of genes involved in the mitochondrial UPR mt |
10.7554/elife.45506 | 41,498,255 | Tail-anchored (TA) proteins insert post-translationally into the endoplasmic reticulum (ER), the outer mitochondrial membrane (OMM) and peroxisomes. Whereas the GET pathway controls ER-targeting, no dedicated factors are known for OMM insertion, posing the question of how accuracy is achieved. The mitochondrial AAA-ATP... | 10.1038/s41580-020-00300-2 | Together with reference 145, this article reports that components of the ER-associated degradation pathway cooperate with Msp1 in the removal of mislocalized proteins from the outer mitochondrial membrane |
10.1038/s41422-020-0323-8 | 103,767,492 | Abstract The multifaceted organization of the immune system involves not only patrolling lymphocytes that constantly monitor antigen-presenting cells in secondary lymphoid organs but also immune cells that establish permanent tissue-residency. The integration in the respective tissue and the adaption to the organ milie... | 10.1038/s41590-022-01299-8 | This review summarizes the emerging roles of innate lymphoid cells in tissue homeostasis and inflammation. |
10.1126/science.aaz8777 | 132,719,627 | Group 3 innate lymphoid cells (ILC3s) are innate immune effectors that contribute to host defense. Whether ILC3 functions are stably modified after pathogen encounter is unknown. Here, we assess the impact of a time-restricted enterobacterial challenge to long-term ILC3 activation in mice. We found that intestinal ILC3... | 10.1038/s41590-022-01299-8 | This article describes the role of ILC3 cells after pathogen rechallenge and the existence of memory ILC3 cells. |
10.1182/blood-2016-09-740563 | 81,523,004 | Key Points Numerous empty HSC niches, located distantly from filled niches, are available for engraftment and proliferation in bone marrow. Presumptive niches for granulocyte/macrophage progenitors appear to be filled in bone marrow. | 10.1038/s41577-022-00698-0 | This work is the first demonstration of robust HSC engraftment without conditioning in immunocompetent mice. |
10.1126/science.278.5335.45 | 62,117,580 | Scientific advances over the past 20 years have shown that drug addiction is a chronic, relapsing disease that results from the prolonged effects of drugs on the brain. As with many other brain diseases, addiction has embedded behavioral and social-context aspects that are important parts of the disorder itself. Theref... | 10.1038/s41583-020-0378-z | An influential opinion piece that popularized the notion of addiction as a brain disease |
10.1126/science.282.5387.298 | 41,511,080 | Differential access to cocaine self-administration produced two patterns of drug intake in rats. With 1 hour of access per session, drug intake remained low and stable. In contrast, with 6 hours of access, drug intake gradually escalated over days. After escalation, drug consumption was characterized by an increased ea... | 10.1038/s41583-020-0378-z | An influential article that introduces the escalation model currently used by numerous researchers |
10.1126/science.1099020 | 62,205,414 | Although the voluntary intake of drugs of abuse is a behavior largely preserved throughout phylogeny, it is currently unclear whether pathological drug use (“addiction”) can be observed in species other than humans. Here, we report that behaviors that resemble three of the essential diagnostic criteria for addiction ap... | 10.1038/s41583-020-0378-z | An important article describing the development of the conceptually influential individual differences DSM-IV rat model |
10.1083/jcb.201807108 | 38,437,770 | While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. In this study, we describe TSA-Seq, a new mapping method capable of providing a “cytological ruler” for estimating mean chromoso... | 10.1038/s41580-021-00362-w | This article introduces TSA-seq, a cytological ruler for nuclear speckles and lamina, which is the first genomics method enabling transforming sequencing reads into physical distances in the nucleus |
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/s41580-021-00362-w | This study uses high-throughput oligopaint technology to study chromatin dynamics and shows that TADs are highly stochastic in single cells, but predictable at the population level |
10.1093/nar/gkaa087 | 37,907,181 | Abstract The rapid development of Chromosome Conformation Capture (3C-based techniques), as well as imaging together with bioinformatics analyses, has been fundamental for unveiling that chromosomes are organized into the so-called topologically associating domains or TADs. While TADs appear as nested patterns in the 3... | 10.1038/s41580-021-00362-w | This paper presents one of the most recently developed TAD callers and is extremely valuable for its benchmarking quality and for multiple TAD caller comparisons |
10.1186/s13059-020-02253-3 | 59,248,740 | Abstract We report SPIN, an integrative computational method to reveal genome-wide intranuclear chromosome positioning and nuclear compartmentalization relative to multiple nuclear structures, which are pivotal for modulating genome function. As a proof-of-principle, we use SPIN to integrate nuclear compartment mapping... | 10.1038/s41580-021-00362-w | This article presents the first tool that combines nuclear architecture (positioning) data from TSA-seq and DamID in order to compute spatial compartmentalization of chromatin in respect to the lamina or nuclear bodies such as nuclear speckles |
10.1126/science.aat7487 | 104,348,880 | By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization’s decline, its people mixed with individuals in the southeast to form on... | 10.1038/s41576-020-0218-z | This work explores the movements of people in the past thousands of years and the formation of a male-biased genetic cline from Central Asia into South Asia, which may be associated with the spread of Indo-European languages and other social transformation events |
10.1073/pnas.1820210116 | 29,088,685 | The third millennium BCE was a period of major cultural and demographic changes in Europe that signaled the beginning of the Bronze Age. People from the Pontic steppe expanded westward, leading to the formation of the Corded Ware complex and transforming the genetic landscape of Europe. At the time, the Globular Amphor... | 10.1038/s41576-020-0218-z | The genetic analysis of a Late Neolithic Polish mass grave with 15 bodies exposed the kinship links among the people buried in this dramatic episode at the time of the arrival of the Eurasian Steppe nomads |
10.1126/science.aax6219 | 29,129,417 | Revealing and understanding the mechanisms behind social inequality in prehistoric societies is a major challenge. By combining genome-wide data, isotopic evidence, and anthropological and archaeological data, we have gone beyond the dominating supraregional approaches in archaeogenetics to shed light on the complexity... | 10.1038/s41576-020-0218-z | The genetic analysis of several Bronze Age settlements in southern Germany helped to understand the patrilineal social structure underlying genetic transformation in that period |
10.1038/s41467-018-06024-4 | 82,305,327 | Abstract Despite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (fro... | 10.1038/s41576-020-0218-z | This is another example of integration of ancient DNA and several other sources of evidence for past behaviour at an individual site |
10.1126/science.aav4040 | 41,725,216 | We assembled genome-wide data from 271 ancient Iberians, of whom 176 are from the largely unsampled period after 2000 BCE, thereby providing a high-resolution time transect of the Iberian Peninsula. We document high genetic substructure between northwestern and southeastern hunter-gatherers before the spread of farming... | 10.1038/s41576-020-0218-z | This work is an example of the large amount of information that can be generated from a single temporal transect in a specific geographical region. The researchers uncovered a male-biased population turnover during the Bronze Age in the Iberian Peninsula |
10.1073/pnas.1703642114 | 83,038,662 | Mobility is one of the most important processes shaping spatiotemporal patterns of variation in genetic, morphological, and cultural traits. However, current approaches for inferring past migration episodes in the fields of archaeology and population genetics lack either temporal resolution or formal quantification of ... | 10.1038/s41576-020-0218-z | This report presents a statistical method that can estimate how much mobility existed among peoples in a given region during periods for which several ancient genomes are available |
10.1038/s42003-019-0399-1 | 17,098,384 | Abstract Human demography research in grounded on the information derived from ancient DNA and archaeology. For example, the study on the early postglacial dual-route colonisation of the Scandinavian Peninsula is largely based on associating genomic data with the early dispersal of lithic technology from the East Europ... | 10.1038/s41576-020-0218-z | Jensen et al. (2019) and Kashuba et al. (2019). Two seminal studies demonstrating the potential of chewed birch pitch for recovery of ancient DNA |
10.1126/science.aao1807 | 20,852,681 | How early human groups were organized Sequencing ancient hominid remains has provided insights into the relatedness between individuals. However, it is not clear whether ancient humans bred among close relatives, as is common in some modern human cultures. Sikora et al. report genome sequences from four early humans bu... | 10.1038/s41576-020-0218-z | This is a seminal study inferring social and reproductive behaviour among early Late Palaeolithic foragers from ancient genomes |
10.1126/science.1199644 | 62,241,927 | Linguistic and cultural changes are revealed through the analyses of words appearing in books. | 10.1038/s41586-021-03660-7 | In this study, 4% of all books that have been published were digitized and used to examine changes in phonology, word use and the adoption of new technologies over long periods of time |
10.1126/science.1248506 | 62,299,787 | Large errors in flu prediction were largely avoidable, which offers lessons for the use of big data. | 10.1038/s41586-021-03660-7 | This paper shows that the increasing over-prediction of flu prevalence of Google Flu Trends was largely the result of changes to Google’s search algorithm, which altered the terms that people used to find flu-related information |
10.1073/pnas.2006089117 | 39,233,160 | The abundance of media options is a central feature of today’s information environment. Many accounts, often based on analysis of desktop-only news use, suggest that this increased choice leads to audience fragmentation, ideological segregation, and echo chambers with no cross-cutting exposure. Contrary to many of thos... | 10.1038/s41586-021-03660-7 | This study tracked the news consumption of users across mobile and desktop devices and found that most individuals do not self-sort their news consumption by partisanship but, instead, consume news from a diversity of sources including partisan and nonpartisan ones |
10.1177/0894439318788322 | 122,969,409 | While big data offer exciting opportunities to address questions about social behavior, studies must not abandon traditionally important considerations of social science research such as data representativeness and sampling biases. Many big data studies rely on traces of people’s behavior on social media platforms such... | 10.1038/s41586-021-03660-7 | Using survey data, this study finds that younger, wealthier and more technically skilled people tend to use social media and that there were substantial gender and education differences in which platforms people used |
10.1145/1517455.1517456 | 47,824,891 | Computer Science research and practice are raising growing privacy concerns among the public and government. Computer technology's increasing ability to capture, organize, interpret and share data about individuals raises questions about what privacy practices computer science researchers should adopt, if any. These is... | 10.1038/s41586-021-03660-7 | Using census data, this paper shows that 87% of the US population could be uniquely identified by date of birth, postal code and gender; demonstrating the ease with which study respondents can be re-identified from ostensibly anonymous data |
10.1002/adfm.201900247 | 83,491,125 | Abstract Nickel‐rich layered materials LiNi 1‐x‐y Mn x Co y O 2 are promising candidates for high‐energy‐density lithium‐ion battery cathodes. Unfortunately, they suffer from capacity fading upon cycling, especially with high‐voltage charging. It is critical to have a mechanistic understanding of such fade. Herein, syn... | 10.1038/s41560-022-01021-w | This paper reports the formation of cracks in a NMC cathode at high voltages and provides a particle-level degradation mechanism |
10.1038/s41467-018-08055-3 | 20,265,041 | Abstract Many plants autonomously change morphology and function in response to environmental stimuli or sequences of stimuli. In contrast with the electronically-integrated sensors, actuators, and microprocessors in traditional mechatronic systems, natural systems embody these sensing, actuation, and control functions... | 10.1038/s41586-021-03623-y | Demonstrates environmentally responsive mechanical logic by using bistable beam mechanisms and stimuli-responsive materials |
10.1098/rspa.2014.0182 | 38,246,477 | Computing is a high-level process of a physical system. Recent interest in non-standard computing systems, including quantum and biological computers, has brought this physical basis of computing to the forefront. There has been, however, no consensus on how to tell if a given physical system is acting as a computer or... | 10.1038/s41586-021-03623-y | Provides a framework for unconventional computing, distinguishing abstract computation from physical embodiment |
10.1038/s41467-019-08678-0 | 107,207,690 | Abstract Early examples of computers were almost exclusively based on mechanical devices. Although electronic computers became dominant in the past 60 years, recent advancements in three-dimensional micro-additive manufacturing technology provide new fabrication techniques for complex microstructures which have rekindl... | 10.1038/s41586-021-03623-y | Realizes a full set of digital mechanical logic gates via 3D printing of bistable flexural beams |
10.1073/pnas.1604838113 | 59,251,555 | Soft structures with rationally designed architectures capable of large, nonlinear deformation present opportunities for unprecedented, highly tunable devices and machines. However, the highly dissipative nature of soft materials intrinsically limits or prevents certain functions, such as the propagation of mechanical ... | 10.1038/s41586-021-03623-y | Demonstrates mechanical diodes and logic gates based on the propagation of stable, nonlinear transition waves in architected soft systems of coupled bistable beams |
10.1038/s41467-017-00670-w | 82,824,344 | Abstract Origami has recently received significant interest from the scientific community as a method for designing building blocks to construct metamaterials. However, the primary focus has been placed on their kinematic applications by leveraging the compactness and auxeticity of planar origami platforms. Here, we pr... | 10.1038/s41586-021-03623-y | Demonstrates volumetric origami cells with tuneable stability and stiffness that store bit information in a bistable potential-energy landscape |
10.1073/pnas.1805122115 | 102,283,463 | Robots autonomously interact with their environment through a continual sense–decide–respond control loop. Most commonly, the decide step occurs in a central processing unit; however, the stiffness mismatch between rigid electronics and the compliant bodies of soft robots can impede integration of these systems. We dev... | 10.1038/s41586-021-03623-y | Presents an environmentally responsive origami platform using the waterbomb fold pattern as a mechanical storage device that writes, erases and rewrites itself in response to a time-varying environmental signal |
10.1063/1.3511343 | 57,213,124 | We investigate the nonlinear dynamics of microcantilevers. We demonstrate mechanical stiffening of the frequency response at large amplitudes, originating from the geometric nonlinearity. At strong driving the cantilever amplitude is bistable. We map the bistable regime as a function of drive frequency and amplitude, a... | 10.1038/s41586-021-03623-y | Utilizes nonlinear dynamics in microcantilevers to demonstrate bit operations in volatile dynamic systems through modulation of the driving frequency |
10.1073/pnas.1618314114 | 123,067,984 | The realization of acoustic devices analogous to electronic systems, like diodes, transistors, and logic elements, suggests the potential use of elastic vibrations (i.e., phonons) in information processing, for example, in advanced computational systems, smart actuators, and programmable materials. Previous experimenta... | 10.1038/s41586-021-03623-y | Uses geometric nonlinearities to switch and amplify elastic vibrations via magnetic coupling, allowing logic and simple calculations |
10.1073/pnas.1218599110 | 104,253,229 | Immunoresponsive gene 1 ( Irg1 ) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify Irg1 as the gene coding for an enzyme producing itaconic acid (also known as methylenesuccinic acid) through the decarboxylation of cis -aconitate... | 10.1038/s41577-019-0124-9 | This study reports the identification of Irg1 as encoding an enzyme that generates itaconate and the finding that itaconate is a potent antimicrobial molecule that can block the growth of intracellular M. tuberculosis and Salmonella spp |
10.1073/pnas.0711159105 | 125,260,579 | A hallmark of tuberculosis is the ability of the causative agent, Mycobacterium tuberculosis , to persist for decades despite a vigorous host immune response. Previously, we identified a mycobacterial gene cluster, mce4 , that was specifically required for bacterial survival during this prolonged infection. We now show... | 10.1038/s41577-019-0124-9 | This study identifies the Mce4 membrane protein complex as the primary transporter of cholesterol in M. tuberculosis and shows that the activity of this transporter is necessary for maintenance of M. tuberculosis infection in vivo |
10.1126/science.1244705 | 83,085,476 | Persistent Survival The role of persister cells—dormant cells that survive multidrug treatment—in the context of bacterial pathogenesis has not been explored in depth. Using a single-cell fluorescent dilution technique, Helaine et al. (p. 204 ) examined Salmonella Typhimurium persister-cell formation in vitro and in in... | 10.1038/s41577-019-0124-9 | In this study, a green fluorescent protein-dilution reporter strain is used to examine non-replicating Salmonella spp. bacteria in vivo and to show that, in vitro, IFNγ-activated macrophages induce markedly higher levels of drug tolerance in Salmonella spp. than do resting macrophages. |
10.1084/jem.20172020 | 62,078,902 | To understand how infection by Mycobacterium tuberculosis (Mtb) is modulated by host cell phenotype, we characterized those host phagocytes that controlled or supported bacterial growth during early infection, focusing on the ontologically distinct alveolar macrophage (AM) and interstitial macrophage (IM) lineages. Usi... | 10.1038/s41577-019-0124-9 | This is a recent study showing that macrophages of different developmental lineages differentially support the growth of M. tuberculosis in vivo and that alveolar macrophages are more permissive for bacterial growth than are interstitial macrophages through metabolism-dependent mechanisms |
10.1038/s41467-020-15383-w | 41,068,003 | Abstract Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10 −12 ) and... | 10.1038/s41581-020-0325-2 | This investigation identified two additional risk alleles for idiopathic membranous nephropathy and examines the ancestry-specific effects of variation at the HLA locus. Using the genome-wide significant risk loci detected, they create a genetic risk score that can correctly reclassify up to 37% of affected individuals... |
10.1126/science.aay0256 | 82,869,278 | Transcriptome data can facilitate the interpretation of the effects of rare genetic variants. Here, we introduce ANEVA (analysis of expression variation) to quantify genetic variation in gene dosage from allelic expression (AE) data in a population. Application of ANEVA to the Genotype-Tissues Expression (GTEx) data sh... | 10.1038/s41581-020-0325-2 | This study incorporated tissue-specific and population-level RNA sequencing data to identify causal genes among patients with genetically unresolved disease, demonstrating the utility of transcriptomics for the diagnosis of rare disease |
10.1126/science.aal4043 | 61,275,814 | Hidden effects of Mendelian inheritance Identifying the determinate factors of genetic disease has been quite successful for Mendelian inheritance of large-effect pathogenic variants. In these cases, two non- or low-functioning genes contribute to disease. However, Mendelian effects of lesser strength have generally be... | 10.1038/s41581-020-0325-2 | This study leveraged electronic health record data to develop phenotypic risk scores and used these scores to detect individuals with undiagnosed rare diseases, including multiple monogenic forms of kidney disease |
10.1073/pnas.0705414105 | 20,811,902 | The term “tipping point” commonly refers to a critical threshold at which a tiny perturbation can qualitatively alter the state or development of a system. Here we introduce the term “tipping element” to describe large-scale components of the Earth system that may pass a tipping point. We critically evaluate potential ... | 10.1038/s41586-021-03263-2 | This paper was the first to identify potential tipping elements in the climate system |
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