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10.1126/science.1218198 | 20,705,223 | Genetic exchange is common among bacteria, but its effect on population diversity during ecological differentiation remains controversial. A fundamental question is whether advantageous mutations lead to selection of clonal genomes or, as in sexual eukaryotes, sweep through populations on their own. Here, we show that ... | 10.1038/s41576-018-0032-z | This study provides evidence for ecological differentiation driven by gene-specific (rather than genome-wide) sweeps followed by emergence of barriers to gene flow. |
10.1111/mec.12162 | 4,800,750 | Abstract Hybridization between distantly related organisms can facilitate rapid adaptation to novel environments, but is potentially constrained by epistatic fitness interactions among cell components. The zoonotic pathogens C ampylobacter coli and C . jejuni differ from each other by around 15% at the nucleotide level... | 10.1038/s41576-018-0032-z | This study demonstrates extensive recombination between different bacterial species in the same agricultural niche, which may be relevant to adaptation. |
10.1073/pnas.1305559110 | 122,501,579 | Genome-wide association studies have the potential to identify causal genetic factors underlying important phenotypes but have rarely been performed in bacteria. We present an association mapping method that takes into account the clonal population structure of bacteria and is applicable to both core and accessory geno... | 10.1038/s41576-018-0032-z | This paper presents a GWAS approach for bacteria that takes into account the clonal population structure and that is applicable to both core and accessory genome variation. |
10.1534/genetics.117.300662 | 103,770,318 | Abstract The impact of epistasis on the evolution of multi-locus traits depends on recombination. While sexually reproducing eukaryotes recombine so frequently that epistasis between polymorphisms is not considered to play a large role in short-term adaptation, many bacteria also recombine, some to the degree that thei... | 10.1038/s41576-018-0032-z | This paper describes a quantitative analysis of the role of epistasis in bacterial adaptation. |
10.1073/pnas.0406993102 | 103,095,340 | Understanding bacterial population genetics is vital for interpreting the response of bacterial populations to selection pressures such as antibiotic treatment or vaccines targeted at only a subset of strains. The evolution of transmissible bacteria occurs by mutation and localized recombination and is influenced by ep... | 10.1038/s41576-018-0032-z | This paper provides a neutral explanation for bacterial population structure and challenges the assumption that strains differ markedly in relative fitness. |
10.1126/science.1127573 | 83,342,016 | Genetic surveys reveal the diversity of bacteria and lead to the questioning of species concepts used to categorize bacteria. One difficulty in defining bacterial species arises from the high rates of recombination that results in the transfer of DNA between relatively distantly related bacteria. Barriers to this proce... | 10.1038/s41576-018-0032-z | This paper highlights the importance of recombination rates in the processes of adaptation and speciation. |
10.1038/s41598-017-09483-9 | 109,433,706 | Abstract Horizontal gene transfer accelerates bacterial adaptation to novel environments, allowing selection to act on genes that have evolved in multiple genetic backgrounds. This can lead to ecological specialization. However, little is known about how zoonotic bacteria maintain the ability to colonize multiple hosts... | 10.1038/s41576-018-0032-z | This paper explains how observed gradients of host specialism and generalism can evolve in a multi-host system through the transfer of ecologically important loci among coexisting strains. |
10.1101/2022.07.06.22277335 | 142,667,859 | Abstract Both common and rare genetic variants influence complex traits and common diseases. Genome-wide association studies have discovered thousands of common-variant associations, and more recently, large-scale exome sequencing studies have identified rare-variant associations in hundreds of genes 1–3 . However, rar... | 10.1038/s41586-019-1879-7 | The most recent report from the genome aggregation database (gnomAD) project combining human sequence data on an unprecedented scale to characterize rare, high-impact variants and their relationship to health and disease. |
10.1126/science.273.5281.1516 | 83,118,303 | The identification of the genetic basis of complex human diseases such as schizophrenia and diabetes has proven difficult. In their Perspective, Risch and Merikangas propose that we can best accomplish this goal by combining the power of the human genome project with association studies, a method for determining the ba... | 10.1038/s41586-019-1879-7 | A highly influential commentary that switched much of the complex trait genetics field from linkage to association and imagined GWAS several years before the technology made them a reality. |
10.1126/science.1109557 | 125,249,620 | Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene ( CFH ) is strong... | 10.1038/s41586-019-1879-7 | Arguably the first full GWAS, this study demonstrated the potential of agnostic genomic surveys to highlight entirely novel biology—in this case, a role for complement in the pathogenesis of macular degeneration. |
10.1126/science.aac8624 | 79,658,669 | Rare gene knockouts in adult humans On average, most people's genomes contain approximately 100 completely nonfunctional genes. These loss-of-function (LOF) mutations tend to be rare and/or occur only as a single copy within individuals. Narasimhan et al. investigated LOF in a Pakistani population with high levels of c... | 10.1038/s41586-019-1879-7 | A powerful illustration of the insights that can be gained from the study of individuals who are homozygous carriers of null alleles in genes of biomedical interest. |
10.1038/nature24277 | 41,678,238 | Abstract Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across... | 10.1038/s41586-019-1879-7 | One of several papers describing the results obtained from the Genotype-Tissue Expression (GTEx) project, which used RNA-sequence data from more than 40 human tissues in several hundred individuals to explore the relationship between DNA sequence variation and tissue-specific expression. |
10.1111/his.12592 | 124,644,434 | Microscopic colitis has emerged as a major cause of chronic watery non‐bloody diarrhoea, particularly in elderly females. The term is used as an umbrella term to categorize a subgroup of colitides with distinct clinicopathological phenotypes and no significant endoscopic abnormalities. Lymphocytic colitis is defined by... | 10.1038/s41572-021-00273-2 | This paper is a comprehensive review of the histological findings in MC. |
10.1111/apt.15246 | 125,317,707 | Summary Background Epidemiological studies of microscopic colitis have shown varying but increasing incidence rates. Aim To assess the incidence of microscopic colitis in Sweden. Methods Nationwide cohort study performed in 1995‐2015 based on biopsy reports. Age‐specific and age‐standardised incidence rates were calcul... | 10.1038/s41572-021-00273-2 | A nationwide cohort study demonstrating the incidence of MC by calendar year, sex and disease subtype. This study provides the most recent estimates of the lifetime prevalence of the disease. |
10.1177/2050640620951905 | 17,577,097 | Abstract Introduction Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic... | 10.1038/s41572-021-00273-2 | This paper describes the European guidelines for diagnosis and management of MC. |
10.1111/apt.16142 | 150,844,955 | Summary Background Colitis is a significant complication of immune checkpoint inhibitors (ICI). Currently, clinical and endoscopic severity are used to guide therapy. Aims To investigate associations between clinical, endoscopic, and histological features with outcomes Methods We identified 149 patients from seven inst... | 10.1038/s41572-021-00273-2 | This paper describes MC induced by checkpoint inhibitors, a complication that will be increasingly observed with the growing use of these agents in cancer therapy. |
10.1136/gutjnl-2015-309934 | 18,538,877 | Objective Collagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predi... | 10.1038/s41572-021-00273-2 | The first genetic association study demonstrating the relationship between HLA variants and collagenous colitis. |
10.1136/gutjnl-2016-313051 | 83,548,012 | Objective Microscopic colitis (MC) is a common cause of chronic diarrhoea, often with additional symptoms. No validated instruments exist to assess disease activity in MC, making it difficult to compare efficacy of treatments between clinical trials. We aimed to identify clinical features that independently predicted d... | 10.1038/s41572-021-00273-2 | This study established the first disease activity index for MC as a non-invasive marker for use in clinical trials. |
10.1111/apt.14133 | 62,597,806 | Summary Background Microscopic colitis ( MC ) is a common cause of chronic diarrhoea. Various treatment options have been described, but there are limited data describing outcomes of corticosteroid‐sparing treatments. Aim To evaluate the outcomes of patients with active MC treated with immune modulators. Methods All pa... | 10.1038/s41572-021-00273-2 | The largest case series of thiopurines, methotrexate and TNF antagonists for the management of budesonide-refractory MC. |
10.1111/epi.13709 | 104,431,235 | Summary The International League Against Epilepsy ( ILAE ) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical ... | 10.1038/s41593-022-01053-1 | A consensus article from the International League Against Epilepsy defining epilepsy syndromes and reviewing underlying etiologies |
10.1126/science.1252304 | 104,321,678 | On-Demand Activity Oligodendroglia ensheath axons in the brain with myelin, which provides the insulation that speeds up transmission of neuronal electrical impulses. The process of myelination in the human brain goes on for decades, concurrent with all manner of brain development and cognitive activity. Gibson et al. ... | 10.1038/s41593-022-01053-1 | Neuronal activity can promote circuit-specific oligodendrocyte precursor cell proliferation, oligodendrocyte generation and adaptive myelination that influences behavioral function |
10.1073/pnas.1916646117 | 123,949,051 | Communication and oscillatory synchrony between distributed neural populations are believed to play a key role in multiple cognitive and neural functions. These interactions are mediated by long-range myelinated axonal fiber bundles, collectively termed as white matter. While traditionally considered to be static after... | 10.1038/s41593-022-01053-1 | Computational results indicating that activity-regulated myelination promotes phase synchronization of neural oscillators and stabilizes oscillatory neural activity |
10.1073/pnas.1101595108 | 20,263,240 | Interactions between bacteria and the viruses that infect them (i.e., phages) have profound effects on biological processes, but despite their importance, little is known on the general structure of infection and resistance between most phages and bacteria. For example, are bacteria–phage communities characterized by c... | 10.1038/s41579-021-00612-w | Demonstrates the role of virus host range in generating community-wide patterns of host–phage interactions |
10.1038/ismej.2016.160 | 122,683,322 | Abstract The genus Micromonas comprises phytoplankton that show among the widest latitudinal distributions on Earth, and members of this genus are recurrently infected by prasinoviruses in contrasted thermal ecosystems. In this study, we assessed how temperature influences the interplay between the main genetic clades ... | 10.1038/s41579-021-00612-w | Shows the effect of temperature on the kinetics, phenotypes and life history strategies of prasinoviruses |
10.1073/pnas.1401322111 | 17,715,815 | Significance Within aquatic ecosystems viruses facilitate horizontal gene transfer, biogeochemical cycling, and energy transfer by infecting and lysing microbial host cells. Despite their critical role in ecosystem function we understand little of the biological, ecological, and evolutionary features of most viruses in... | 10.1038/s41579-021-00612-w | Demonstrates that genomic features in the viral replicon (that is, module of genes responsible for viral genome replication) may predict the biogeographical distribution of viruses |
10.1073/pnas.1120310109 | 123,597,612 | Marine viruses impose a heavy mortality on their host bacteria, whereas at the same time the degree of viral resistance in marine bacteria appears to be high. Antagonistic coevolution—the reciprocal evolutionary change of interacting species—might reconcile these observations, if it leads to rapid and dynamic levels of... | 10.1038/s41579-021-00612-w | Demonstrates the rapid co-evolution of virus and host but highlights the challenge of identifying the critical phenotypes mediating the interaction |
10.1073/pnas.1620500114 | 103,560,136 | The eukaryotic CMG (Cdc45, Mcm2–7, GINS) helicase consists of the Mcm2–7 hexameric ring along with five accessory factors. The Mcm2–7 heterohexamer, like other hexameric helicases, is shaped like a ring with two tiers, an N-tier ring composed of the N-terminal domains, and a C-tier of C-terminal domains; the C-tier con... | 10.1038/s41594-018-0024-x | This study reports a high-resolution structure of S. cerevisiae CMG at a replication fork and shows that CMG is oriented on DNA in a direction opposite to that predicted by conventional models. |
10.1073/pnas.1701252114 | 122,120,397 | We present a structure of the ∼650-kDa functional replisome of bacteriophage T7 assembled on DNA resembling a replication fork. A structure of the complex consisting of six domains of DNA helicase, five domains of RNA primase, two DNA polymerases, and two thioredoxin (processivity factor) molecules was determined by si... | 10.1038/s41594-018-0024-x | This study presents a cryo-EM organization of the T7 phage polymerases relative to the helicase–primase. |
10.1073/pnas.0602400103 | 41,647,313 | The protein Cdc45 plays a critical but poorly understood role in the initiation and elongation stages of eukaryotic DNA replication. To study Cdc45's function in DNA replication, we purified Cdc45 protein from Drosophila embryo extracts by a combination of traditional and immunoaffinity chromatography steps and found t... | 10.1038/s41594-018-0024-x | This report demonstrated that an active eukaryotic CMG helicase is a stable 11-subunit complex, a 'holy grail', landmark finding for the field. |
10.1038/ncomms10708 | 81,643,567 | Abstract The Cdc45-MCM-GINS (CMG) helicase unwinds DNA during the elongation step of eukaryotic genome duplication and this process depends on the MCM ATPase function. Whether CMG translocation occurs on single- or double-stranded DNA and how ATP hydrolysis drives DNA unwinding remain open questions. Here we use cryo-e... | 10.1038/s41594-018-0024-x | The authors infer a cooperation, possibly due to twisting between the C tier and N tier, for translocation rather than a staircase process. |
10.1073/pnas.1700530114 | 20,157,345 | The replisome unwinds and synthesizes DNA for genome duplication. In eukaryotes, the Cdc45–MCM–GINS (CMG) helicase and the leading-strand polymerase, Pol epsilon, form a stable assembly. The mechanism for coupling DNA unwinding with synthesis is starting to be elucidated, however the architecture and dynamics of the re... | 10.1038/s41594-018-0024-x | This cryo-EM study reveals flexible positions of the catalytic domain of Pol ℇ bound to CMG. |
10.1146/annurev-pathol-052016-100127 | 104,188,848 | Notch receptors influence cellular behavior by participating in a seemingly simple signaling pathway, but outcomes produced by Notch signaling are remarkably varied depending on signal dose and cell context. Here, after briefly reviewing new insights into physiologic mechanisms of Notch signaling in healthy tissues and... | 10.1038/s41573-020-00091-3 | This article provides a comprehensive review of the multiple roles of Notch signalling in cancer |
10.1158/0008-5472.can-15-1640-t | 100,548,358 | Abstract Approximately 30% of triple-negative breast cancers (TNBC) harbor molecular alterations in PI3K/mTOR signaling, but therapeutic inhibition of this pathway has not been effective. We hypothesized that intrinsic resistance to TORC1/2 inhibition is driven by cancer stem cell (CSC)-like populations that could be t... | 10.1038/s41573-020-00091-3 | This study implicates Notch-dependent CSCs in mTOR complex 1/2 resistance in TNBC |
10.1158/1538-7445.am2018-2839 | 72,480,011 | Abstract EGFR tyrosine kinase inhibitors (EGFR-TKIs) usually cause dramatic responses in EGFR-mutant lung cancer, but different patients with identical drivers have widely different progression-free intervals, and resistance universally develops. In those cases without pre-existing resistant clones, even though every c... | 10.1038/s41573-020-00091-3 | This study supports a novel non-canonical function of NOTCH3 via β-catenin signalling in TKI resistance in NSCLC |
10.1038/s41598-018-22252-6 | 50,869,697 | Abstract Axl is a tyrosine kinase receptor that is commonly overexpressed in many cancers. As such, Axl represents an attractive therapeutic target. The transfer of engineered T cell expressing chimeric antigen receptor (CAR) is an exciting cancer therapeutic approach that shows high efficacy against cancers in clinica... | 10.1038/s41573-020-00091-3 | This study demonstrates the feasibility of the synNotch receptor approach in adoptive cell therapy for cancer |
10.1158/0008-5472.can-15-2528 | 19,544,022 | Abstract Myeloid-derived suppressor cells (MDSC) contribute to immune suppression in cancer, but the mechanisms through which they drive metastatic progression are not fully understood. In this study, we show how MDSC convey stem-like qualities to breast cancer cells that coordinately help enable immune suppression and... | 10.1038/s41573-020-00091-3 | Peng et al. (2016) and Shen et al. (2017) describe Notch-mediated crosstalk between stroma and breast cancer stem cells |
10.1158/0008-5472.can-17-0357 | 61,631,745 | Abstract Myeloid-derived suppressor cells (MDSC) are a major obstacle to promising forms of cancer immunotherapy, but tools to broadly limit their immunoregulatory effects remain lacking. In this study, we assessed the therapeutic effect of the humanized anti–Jagged1/2-blocking antibody CTX014 on MDSC-mediated T-cell s... | 10.1038/s41573-020-00091-3 | This study supports the potential of Jagged 1 as a therapeutic target in cancer immunotherapy |
10.15252/emmm.201607265 | 28,033,546 | Abstract γ‐Secretase inhibitors ( GSI s) are being actively repurposed as cancer therapeutics based on the premise that inhibition of NOTCH 1 signaling in select cancers is therapeutic. Using novel assays to probe effects of GSI s against a broader panel of substrates, we demonstrate that clinical GSI s are pharmacolog... | 10.1038/s41573-020-00091-3 | This study highlights the different pharmacological properties and anti-CSC activity of different classes of investigational GSIs |
10.1073/pnas.0910060107 | 36,760,977 | Survival of differentiated cells is one of several processes regulated by Notch activity, although the general principles underlying this function remain to be characterized. Here, we probe the mechanism underlying Notch-mediated survival, building on emerging evidence that apoptotic responses coordinated by specialize... | 10.1038/s41573-020-00091-3 | Perumalsamy et al. (2010) and Lee et al. (2013) describe mitochondrial Notch pathways in T cells and glioma stem cells, respectively |
10.1038/s41593-021-00982-7 | 133,228,860 | Abstract Guided by gut sensory cues, humans and animals prefer nutritive sugars over non-caloric sweeteners, but how the gut steers such preferences remains unknown. In the intestine, neuropod cells synapse with vagal neurons to convey sugar stimuli to the brain within seconds. Here, we found that cholecystokinin (CCK)... | 10.1038/s41583-022-00613-5 | This paper demonstrates that sugar preference arises from neuropod cells labelled by the CCK promoter in the proximal small intestine |
10.1073/pnas.0706678104 | 62,595,637 | Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1). Regulation of this protein is important for the provision of glucose to the body and avoidance of intestinal malabsorption. Although expression of SGLT1 is regulated by lum... | 10.1038/s41583-022-00613-5 | This study demonstrated a function for enteroendocrine expression of taste receptors and gustducin |
10.1126/science.aat5236 | 41,704,576 | The brain is thought to sense gut stimuli only via the passive release of hormones. This is because no connection has been described between the vagus and the putative gut epithelial sensor cell—the enteroendocrine cell. However, these electrically excitable cells contain several features of epithelial transducers. Usi... | 10.1038/s41583-022-00613-5 | This paper demonstrated the existence of synaptic neurotransmission in the intestine between neuropod cells and vagal neurons |
10.1152/ajpregu.00432.2015 | 82,416,574 | Recent findings suggest that the intestinal sodium-glucose transporter 1 (SGLT1) glucose transporter and sensor mediates, in part, the appetite-stimulation actions of intragastric (IG) glucose and nonmetabolizable α-methyl-d-glucopyranoside (MDG) infusions in mice. Here, we investigated the role of SGLT1 in sugar condi... | 10.1038/s41583-022-00613-5 | This study showed that SGLT1 is the sensor for reward from intestinal glucose |
10.1101/gad.183500 | 41,471,951 | In mammals, circadian oscillators exist not only in the suprachiasmatic nucleus, which harbors the central pacemaker, but also in most peripheral tissues. It is believed that the SCN clock entrains the phase of peripheral clocks via chemical cues, such as rhythmically secreted hormones. Here we show that temporal feedi... | 10.1038/s41568-020-0291-9 | This study illustrates that peripheral clocks are entrained by timed food intake and highlights the role of food as a zeitgeber |
10.1126/science.1226339 | 104,292,993 | Transcription Around the Clock The biological clock that controls daily rhythms in mammalian physiology and behavior is thought to be regulated in large part by transcriptional events (see the Perspective by Doherty and Kay ). Koike et al. (p. 349 ; published online 30 August) produced a comprehensive analysis of these... | 10.1038/s41568-020-0291-9 | This study identifies the parallel between circadian transcriptional regulation and temporal patterns of genome-wide occupancy of core circadian clock regulators |
10.1126/science.1171641 | 20,628,719 | Circadian Oscillations The 24-hour day-night cycle plays an important role in mammalian physiology and behavior and, as most travelers are well aware, there is an intimate link between our in-built circadian clocks and metabolic rhythms. This link is in part forged by the protein deacetylase SIRT1, which regulates the ... | 10.1038/s41568-020-0291-9 | Together with Nakahata et al. (2009), this paper uncovers the link between the core circadian clock and the cyclic production of NAD + through a metabolic feedback loop |
10.1126/science.1243417 | 125,142,483 | Dinner Time! Biological clocks allow organisms to anticipate cycles of feeding, activity, and rest so that metabolic enzymes in mitochondria are ready when needed. Peek et al. ( 10.1126/science.1243417 , published online 19 September; see the Perspective by Rey and Reddy ) describe a mechanism by which the biochemical ... | 10.1038/s41568-020-0291-9 | This study demonstrates that loss of Bmal1 induces a metabolic switch from lipid oxidation to glycolysis |
10.1084/jem.20140570 | 105,406,291 | The transcription factor Gata6 regulates proliferation and differentiation of epithelial and endocrine cells and cancers. Among hematopoietic cells, Gata6 is expressed selectively in resident peritoneal macrophages. We thus examined whether the loss of Gata6 in the macrophage compartment affected peritoneal macrophages... | 10.1038/s41590-019-0407-0 | Refs. 23–25 provide intriguing insights into the unique metabolic and other requirements of macrophages that are adapted to reside within in the peritoneal cavity |
10.1126/science.1224820 | 41,757,817 | Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-s... | 10.1038/s41577-021-00534-x | This study demonstrates the link between intestinal inflammation and the expansion of microbial populations with genotoxic properties |
10.1038/ncomms15781 | 102,015,133 | Abstract Type-2 innate lymphoid cells (ILC2) are a prominent source of type II cytokines and are found constitutively at mucosal surfaces and in visceral adipose tissue. Despite their role in limiting obesity, how ILC2s respond to high fat feeding is poorly understood, and their direct influence on the development of a... | 10.1038/s41577-021-00584-1 | This study uses atherosclerotic mouse models that were deficient in group 2 innate lymphoid cells to prove that IL-5 and IL-13 production by innate lymphoid cells has an atheroprotective role and to highlight the functional overlap between innate lymphoid cells and T H cell subsets in modulating atherosclerosis |
10.1084/jem.20150900 | 17,633,384 | Abnormal glucose metabolism and enhanced oxidative stress accelerate cardiovascular disease, a chronic inflammatory condition causing high morbidity and mortality. Here, we report that in monocytes and macrophages of patients with atherosclerotic coronary artery disease (CAD), overutilization of glucose promotes excess... | 10.1038/s41577-021-00584-1 | This study identifies the glycolytic enzyme pyruvate kinase M2 as a crucial molecular link between altered metabolic adaptations and increased inflammation and oxidative stress in monocytes and macrophages from patients with coronary artery disease |
10.1093/eurheartj/ehy124 | 20,550,538 | Abstract Aims Identification and treatment of the rupture prone atherosclerotic plaque remains a challenge for reducing the burden of cardiovascular disease. The interconnection of metabolic and inflammatory processes in rupture prone plaques is poorly understood. Herein, we investigate associations between metabolite ... | 10.1038/s41577-021-00584-1 | This study conducts targeted metabolic profiling of human carotid plaques and identifies distinct metabolic signatures that distinguish high-risk atherosclerotic plaques from low-risk atherosclerotic plaques |
10.1042/bj3120725 | 83,185,631 | Albumin is a multifunctional transport protein that binds a wide variety of endogenous substances and drugs. Insulins with affinity for albumin were engineered by acylation of the epsilon-amino group of LysB29 with saturated fatty acids containing 10-16 carbon atoms. The association constants for binding of the fatty a... | 10.1038/s41573-022-00529-w | This work is the f irst demonstration of an extended half-life by albumin binding of fatty acid-derivatized peptides |
10.1038/s41598-021-00654-3 | 128,068,052 | Abstract Peptides are notoriously known to display very short in vivo half-lives often measured in minutes which in many cases greatly reduces or eliminates sufficient in vivo efficacy. To obtain long half-lives allowing for up to once-weekly dosing regimen, fatty acid acylation (lipidation) have been used to non-coval... | 10.1038/s41573-022-00529-w | This paper demonstrates the importance of fatty acid position, linker and backbone stability in engineering PYY analogues with long half-lives |
10.1038/s41598-022-05310-y | 133,006,486 | Abstract Prolactin-releasing peptide (PrRP) is an endogenous neuropeptide involved in appetite regulation and energy homeostasis. PrRP binds with high affinity to G-protein coupled receptor 10 (GPR10) and with lesser activity towards the neuropeptide FF receptor type 2 (NPFF2R). The present study aimed to develop long-... | 10.1038/s41573-022-00529-w | This methodological study highlights the differences between monoacid and diacid side chains |
10.1038/s41467-020-17487-9 | 29,101,129 | Abstract Recently, the clinical proof of concept for the first ultra-long oral insulin was reported, showing efficacy and safety similar to subcutaneously administered insulin glargine. Here, we report the molecular engineering as well as biological and pharmacological properties of these insulin analogues. Molecules w... | 10.1038/s41573-022-00529-w | This work presents insights into the development of oral insulin by applying fatty acid derivatization |
10.1038/s41377-018-0103-0 | 81,539,135 | Abstract Optical activation of neurons requires genetic manipulation or the use of chemical photoactivators with undesirable side effects. As a solution to these disadvantages, here, we demonstrate optically evoked neuronal activity in mouse cortical neurons in acute slices and in vivo by nonlinear excitation of gold n... | 10.1038/s41592-021-01270-9 | The authors use plasmonic nanoparticles to activate neurons in vitro and in vivo using two-photon lasers |
10.1038/s41467-018-04383-6 | 19,986,105 | Abstract Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitat... | 10.1038/s41467-019-11812-7 | •This study reports multi-parametric integrative analyses of multiple histone modifications, RNA-seq-based gene expression, and DNA methylation to define comprehensive epigenomic landscapes for PDAC subtypes, which predict relative aggressiveness and survival |
10.1073/pnas.79.24.7824 | 102,387,117 | Human sequences related to the transforming gene (v-myc) of avian myelocytomatosis virus (MC29) are represented by at least one gene and several related sequences that may represent pseudogenes. By using a DNA probe that is specific for the complete gene (c-myc), different somatic cell hybrids possessing varying number... | 10.1038/s41572-022-00404-3 | Molecular study showing that oncogene is the gene involved in the chromosomal aberration t(8;14) in BL |
10.1182/blood-2018-09-871418 | 83,356,217 | Abstract Although generally curable with intensive chemotherapy in resource-rich settings, Burkitt lymphoma (BL) remains a deadly disease in older patients and in sub-Saharan Africa. Epstein-Barr virus (EBV) positivity is a feature in more than 90% of cases in malaria-endemic regions, and up to 30% elsewhere. However, ... | 10.1038/s41572-022-00404-3 | A comprehensive molecular analysis of both EBV + and EBV – BL demonstrated a link between EBV + BL and mutation patterns indicative of aberrant AID expression and function |
10.1002/ijc.24934 | 61,995,879 | Abstract Burkitt lymphoma (BL) is a unique B‐cell non‐Hodgkin lymphoma with 3 established clinical‐epidemiological variants: endemic, sporadic and AIDS‐related BL. BL variants show characteristic dysregulation of MYC gene, but the causes of MYC dysregulation or BL arising at different ages are poorly understood. Theref... | 10.1038/s41572-022-00404-3 | This was the first paper to report multimodal patterns of Burkitt lymphoma the US, suggesting that the molecular forms of Burkitt lymphoma may vary with age at diagnosis, and that mortality patterns vary with age. |
10.1200/jco.20.00303 | 123,031,443 | PURPOSE Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may... | 10.1038/s41572-022-00404-3 | A multicentre prospective study demonstrating the safety and efficacy of low-intensity therapy with dose-adjusted EPOCH-R in adults with Burkitt lymphoma. |
10.1182/bloodadvances.2020002178 | 41,750,268 | Abstract Long-term cure of childhood Burkitt lymphoma (BL) in sub-Saharan Africa after treatment with single-agent cyclophosphamide has been documented for more than half of a century. Contemporary cure rates for the highest-risk patients with BL in high-income countries exceed 90% using intensive multiagent chemothera... | 10.1038/s41572-022-00404-3 | A retrospective study demonstrating the challenges of delivering effective therapy in resource-restricted areas of the world such as sub-Saharan Africa. |
10.1182/blood-2015-01-623900 | 45,479,907 | Key Points We report the first dedicated prospective study in HIV-Burkitt lymphoma demonstrating safety and efficacy in a multi-institutional setting. We offer a new therapeutic option by modifying an existing regimen and making it much less toxic. | 10.1038/s41572-022-00404-3 | A multicenter prospective study demonstrating the feasibility and efficacy of highly dose-intensive chemotherapy with CODOX-M/IVAC in adults with HIV-associated Burkitt lymphoma. |
10.1182/blood.v77.5.1092.bloodjournal7751092 | 34,396,439 | The Epstein-Barr virus (EBV) is associated with distinct forms of human lymphoid malignancies, including the endemic (eBL) and sporadic forms of Burkitt's lymphoma (sBL) and acquired immunodeficiency syndrome- associated non-Hodgkin lymphoma (AIDS-NHL). However, whether EBV has a pathogenetic role in these tumors or is... | 10.1038/s41572-022-00404-3 | This paper demonstrated that EBV was clonal in BL cells and that EBV infection was not secondary to tumorigenesis. |
10.1182/blood-2018-04-844472 | 125,301,734 | Abstract Burkitt lymphoma (BL) is the most common pediatric cancer in sub-Saharan Africa (SSA), and also occurs frequently among adolescents and young adults (AYAs), often associated with HIV. Treating BL in SSA poses particular challenges. Although highly effective, high-intensity cytotoxic treatments used in resource... | 10.1038/s41572-022-00404-3 | A concise review on the treatment approaches for Burkitt lymphoma in resource-restricted areas of the world such as sub-Saharan Africa. |
10.1200/jco.1996.14.3.925 | 123,621,705 | PURPOSE We have used identical treatment protocols for adults and children with small non-cleaved-cell lymphoma (SNCL) for many years and report here the results of two successive treatment regimens in these age groups. PATIENTS AND METHODS Seventy-two patients (39 adults and 33 children) were treated with protocol 77-... | 10.1038/s41572-022-00404-3 | A single institution study in children and young adults with the highly dose-intenstive regimen CODOX-M/IVAC for Burkitt lymphoma that demonstrated very high rates of complete response. |
10.1182/blood-2014-03-563627 | 40,307,649 | Key Points Largest prospective trial for adult Burkitt lymphoma/leukemia patients. Substantial cure rates and high treatment-realization rates in all age groups. | 10.1038/s41572-022-00404-3 | A large multicenter prospective study demonstrating the safety and efficacy of adding rituximab to highly dose-intensive chemotherapy in children and adults with Burkitt lymphoma and Burkitt-like leukaemia. |
10.1038/s41467-020-15064-8 | 41,564,736 | Abstract The flow of fresh groundwater may provide substantial inputs of nutrients and solutes to the oceans. However, the extent to which hydrogeological parameters control groundwater flow to the world’s oceans has not been quantified systematically. Here we present a spatially resolved global model of coastal ground... | 10.1038/s41586-021-04339-9 | A global, spatially resolved quantitative assessment of carbon fluxes through the subsurface, suggesting a relatively minor contribution of the fresh groundwater pathway to the land–ocean exchanges. |
10.5194/bg-13-4167-2016 | 123,153,041 | Abstract. Anthropogenic changes in atmosphere–ocean and atmosphere–land CO2 fluxes have been quantified extensively, but few studies have addressed the connection between land and ocean. In this transition zone, the coastal ocean, spatial and temporal data coverage is inadequate to assess its global budget. Thus we use... | 10.1038/s41586-021-04339-9 | A study quantifying the anthropogenic perturbation of CO 2 uptake by continental shelf waters, suggesting a small pre-industrial sink as further corroborated by the recent work by ref 55 |
10.5194/bg-2-1-2005 | 20,477,686 | Abstract. The carbon burial in vegetated sediments, ignored in past assessments of carbon burial in the ocean, was evaluated using a bottom-up approach derived from upscaling a compilation of published individual estimates of carbon burial in vegetated habitats (seagrass meadows, salt marshes and mangrove forests) to t... | 10.1038/s41586-021-04339-9 | Pioneering study highlighting the quantitative role of coastal vegetation in the fixation, burial and lateral carbon exports to the open ocean and their anthropogenic perturbation. |
10.1038/s41467-017-01789-6 | 103,974,915 | Abstract Burial in sediments removes organic carbon (OC) from the short-term biosphere-atmosphere carbon (C) cycle, and therefore prevents greenhouse gas production in natural systems. Although OC burial in lakes and reservoirs is faster than in the ocean, the magnitude of inland water OC burial is not well constrained... | 10.1038/s41586-021-04339-9 | A study proposing a significant downward revision of the global inland water carbon burial, corroborating the model results on the anthropogenic perturbation by ref 52 |
10.1084/jem.20162024 | 83,542,792 | Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs... | 10.1038/s41573-018-0004-1 | This is the first report that provides precise characterization of CAF heterogeneity in cancer |
10.1073/pnas.1109493108 | 122,991,033 | Increased numbers of S100A4 + cells are associated with poor prognosis in patients who have cancer. Although the metastatic capabilities of S100A4 + cancer cells have been examined, the functional role of S100A4 + stromal cells in metastasis is largely unknown. To study the contribution of S100A4 + stromal cells in met... | 10.1038/s41573-018-0004-1 | This is the first report on the role of stromal cells in remodelling the pre-metastatic soil |
10.1126/science.1195300 | 41,756,396 | Tumor Vaccination Success Vaccination with tumor-specific antigens is one of several attempted therapies seeking to harness the immune system, but—unfortunately—this strategy has been unsuccessful, possibly because of the immunosuppressive properties of the tumor microenvironment. Kraman et al. (p. 827 ; see the Perspe... | 10.1038/s41573-018-0004-1 | This study provides the first evidence that CAFs suppress antitumour immunity |
10.1101/gad.14.9.1048 | 127,316,785 | The corepressor SMRT mediates repression by thyroid hormone receptor (TR) as well as other nuclear hormone receptors and transcription factors. Here we report the isolation of a novel SMRT-containing complex from HeLa cells. This complex contains transducin β-like protein 1 (TBL1), whose gene is mutated in human sensor... | 10.1038/s41580-018-0076-0 | References 29–31 identify the stoichiometric relationship between nuclear receptor co-repressors and HDAC3 |
10.1128/mcb.21.18.6091-6101.2001 | 20,554,487 | ABSTRACT Repression of gene transcription is linked to regulation of chromatin structure through deacetylation of core histone amino-terminal tails. This action is mediated by histone deacetylases (HDACs) that function within active multiprotein complexes directed to the promoters of repressed genes. In vivo, HDAC3 for... | 10.1038/s41580-018-0076-0 | This paper reports that HDAC3 activity requires nuclear receptor co-repressors |
10.1002/ana.410330109 | 62,619,406 | Abstract Both clinical and physiological consideration of migraine suggests that the pathophysiology of the syndrome is intimately linked to the trigeminal innervation of the cranial vessels, the trigeminovascular system. Studies were conducted on cats and humans to examine the interaction of these systems with the eff... | 10.1038/s41582-018-0003-1 | In this study, the measurement of peptides after a migraine attack showed that only CGRP release was increased; subcutaneous sumatriptan normalized CGRP and concurrently reduced headache. |
10.1038/sj.bjp.0703110 | 123,160,239 | Calcitonin gene‐related peptide (CGRP) is one of the most potent endogenous vasodilators known. This peptide is increased during migraine attacks and has been implicated in the pathogenesis of migraine headache. Here we report on the first small molecule selective CGRP antagonist: BIBN4096BS. In vitro , this compound i... | 10.1038/s41582-018-0003-1 | This study is a pharmacological characterization of olcegepant, the first CGRP blocker. |
10.1002/ana.410280213 | 104,391,146 | Abstract The innervation of the cranial vessels by the trigeminal nerve, the trigeminovascular system, has recently been the subject of study in view of its possible role in the mediation of some aspects of migraine. Since stimulation of the trigeminal ganglion in humans leads to facial pain and flushing and associated... | 10.1038/s41582-018-0003-1 | This was the first study to show that CGRP is released, but other peptides are not, in association with migraine attacks. |
10.1073/pnas.83.15.5731 | 41,503,045 | Distribution studies disclosed that all major cerebral arteries and cortical arterioles of the cat were invested with fine varicose nerve fibers that contained calcitonin gene-related peptide (CGRP)-like immunoreactivity; the trigeminal ganglia likewise contained CGRP immunoreactivity. Sequential immunostaining with an... | 10.1038/s41582-018-0003-1 | The first study to demonstrate the trigeminovascular reflex and its dependency on CGRP. |
10.1039/c8ee02751j | 82,805,079 | Halide perovskites are found to exhibit strain patterns over large areas, which influences the lifetimes of charge carriers. | 10.1038/s41578-019-0125-0 | This study provides experimental evidence to suggest that strain is formed in a perovskite film during fabrication and demonstrates this effect at multiple length scales |
10.1126/science.aah5065 | 104,348,243 | The role of the alkali metal cations in halide perovskite solar cells is not well understood. Using synchrotron-based nano–x-ray fluorescence and complementary measurements, we found that the halide distribution becomes homogenized upon addition of cesium iodide, either alone or with rubidium iodide, for substoichiomet... | 10.1038/s41578-019-0125-0 | Study in which the chemical signatures of elements in the perovskite structure are imaged with nanometre resolution and related to solar cell performance |
10.1126/science.aaa5333 | 62,235,945 | Going toward the grains Great strides have been made in improving the efficiency of organic-inorganic perovskite solar cells. Further improvements are likely to depend on understanding the role of film morphology on charge-carrier dynamics. de Quilettes et al. correlated confocal fluorescence microscopy images with tho... | 10.1038/s41578-019-0125-0 | A pioneering study showing that individual grains in the halide perovskite microstructure have heterogeneous emission intensities and lifetimes |
10.1039/c4sc03141e | 125,177,882 | A reversible photo-induced instability has been found in mixed-halide photovoltaic perovskites that limits the open circuit voltage in solar cells. | 10.1038/s41578-019-0125-0 | The first study to experimentally demonstrate light-activated halide ion migration for perovskites with a mixed-halide (I − and Br − ) composition. |
10.1039/c5ee03874j | 20,810,416 | Today's best perovskite solar cells use a mixture of formamidinium and methylammonium as the monovalent cations. Adding cesium improves the compositions greatly. | 10.1038/s41578-019-0125-0 | The first study to incorporate Cs + into the halide perovskite lattice by partially substituting the organic FA + and MA + cations, leading to an increase in performance and stability |
10.1107/s0108768107031758 | 62,663,817 | Three inorganic–organic layered perovskite-type hybrids of the general formula [(C n H 2 n + 1 NH 3 ) 2 PbI 4 ], n = 4, 5 and 6, display a number of reversible first-order phase transitions in the temperature range from 256 to 393 K. [(C 4 H 9 NH 3 ) 2 PbI 4 ] has a single phase transition, [(C 5 H 11 NH 3 ) 2 PbI 4 ] ... | 10.1038/s41565-020-00811-1 | Description of the detailed structural changes taking place during phase transitions in 2DPKs with n = 1 |
10.1038/ncomms13718 | 38,367,507 | Abstract Luminescence imaging has gained attention as a promising bio-imaging modality in situations where fluorescence imaging cannot be applied. However, wider application to multicolour and dynamic imaging is limited by the lack of bright luminescent proteins with emissions across the visible spectrum. Here we repor... | 10.1038/s41592-022-01530-2 | This paper discusses a series of ultrabright reporters for bioluminescence microscopy |
10.1146/annurev-anchem-061318-115027 | 19,030,485 | Although fluorescent reporters and biosensors have become indispensable tools in biological and biomedical fields, fluorescence measurements require external excitation light, thereby limiting their use in thick tissues and live animals. Bioluminescent reporters and biosensors may potentially overcome this hurdle becau... | 10.1038/s41592-022-01530-2 | This Review article highlights bioluminescent biosensors, including various BRET-based reporters |
10.1126/science.1147532 | 82,998,389 | Pulsar surveys offer a rare opportunity to monitor the radio sky for impulsive burst-like events with millisecond durations. We analyzed archival survey data and found a 30-jansky dispersed burst, less than 5 milliseconds in duration, located 3° from the Small Magellanic Cloud. The burst properties argue against a phys... | 10.1038/s41586-020-2828-1 | This discovery paper marks the birth of the FRB research field |
10.1146/annurev-astro-091918-104501 | 123,013,684 | We summarize our understanding of millisecond radio bursts from an extragalactic population of sources. Fast radio bursts (FRBs) occur at an extraordinary rate, thousands per day over the entire sky with radiation energy densities at the source about ten billion times larger than those from Galactic pulsars. We survey ... | 10.1038/s41586-020-2828-1 | This paper is another comprehensive review of the FRB field summarizing the observational properties of FRBs as of 2019 |
10.3847/1538-4357/aa633d | 84,365,682 | Abstract Subarcsecond localization of the repeating fast radio burst FRB 121102 revealed its coincidence with a dwarf host galaxy and a steady (“quiescent”) nonthermal radio source. We show that the properties of the host galaxy are consistent with those of long-duration gamma-ray bursts (LGRB) and hydrogen-poor superl... | 10.1038/s41586-020-2828-1 | This paper proposes that young magnetars born in extreme explosions such as GRBs and superluminous supernovae are the engines of repeating FRBs |
10.1093/mnrasl/slu046 | 20,511,884 | Abstract Bursts of millisecond duration were recently discovered in the 1 GHz band. There is a strong evidence that they come from ∼1 Gpc distances, which implies extraordinary high-brightness temperature. I propose that these bursts could be attributed to synchrotron maser emission from relativistic, magnetized shocks... | 10.1038/s41586-020-2828-1 | This paper first proposes the synchrotron maser coherent mechanism to interpret FRBs |
10.1073/pnas.1717160115 | 103,927,714 | Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and anti... | 10.1038/s41579-019-0288-0 | Extensive review of past antibacterial therapies and opportunities for future strategies to provide new therapies |
10.3390/ijms20061255 | 41,616,608 | Since their discovery in the early 20th century, antibiotics have been used as the primary weapon against bacterial infections. Due to their prophylactic effect, they are also used as part of the cocktail of drugs given to treat complex diseases such as cancer or during surgery, in order to prevent infection. This has ... | 10.1038/s41579-019-0288-0 | An extensive overview of past and current strategies for antibacterial therapies |
10.1002/med.21572 | 62,025,630 | Abstract Bacteriophages are not forgotten viruses anymore: scientists and practitioners seek to understand phage pharmacokinetics in animals and humans, investigating bacteriophages as therapeutics, nanocarriers or microbiome components. This review provides a comprehensive overview of factors that determine phage circ... | 10.1038/s41579-019-0288-0 | Critical challenges in treating bacterial infections at different body sites are reviewed |
10.1098/rstb.2018.0103 | 38,968,351 | Our bodies are colonized by a complex ecosystem of bacteria, unicellular eukaryotes and their viruses that together play a major role in our health. Over the past few years tools derived from the prokaryotic immune system known as CRISPR-Cas have empowered researchers to modify and study organisms with unprecedented ea... | 10.1038/s41579-019-0288-0 | New technologies bring challenges and opportunities for future new therapies that are reviewed in this article |
10.1002/cbic.201900583 | 73,945,663 | Abstract Remarkable technical progress in the area of structural biology has paved the way to study previously inaccessible targets. For example, large protein complexes can now be easily investigated by cryo‐electron microscopy, and modern high‐field NMR magnets have challenged the limits of high‐resolution characteri... | 10.1038/s41570-020-0204-1 | In this concept paper, the authors discuss how site-specific isotopic labelling of individual amino acids of homorepeat regions, which combines nonsense suppression and cell-free protein synthesis, could be exploited as a strategy to obtain high-resolution structural information |
10.1038/s41467-019-09923-2 | 18,680,137 | Abstract Polyglutamine (polyQ) tracts are regions of low sequence complexity frequently found in transcription factors. Tract length often correlates with transcriptional activity and expansion beyond specific thresholds in certain human proteins is the cause of polyQ disorders. To study the structural basis of the ass... | 10.1038/s41570-020-0204-1 | In this paper, the authors provide detailed insights into the non-covalent bonds that stabilize the helical conformation of the polyglutamine repeat region of the androgen receptor. They also discuss how the helix stabilization at increased length might promote aggregation of the androgen receptor, providing a molecula... |
10.1073/pnas.1908790116 | 20,415,751 | Repetitive sequences are hotspots of evolution at multiple levels. However, due to difficulties involved in their assembly and analysis, the role of repeats in tumor evolution is poorly understood. We developed a rigorous motif-based methodology to quantify variations in the repeat content, beyond microsatellites, in p... | 10.1038/s41570-020-0204-1 | In this paper, the authors analyze repeat-instability signatures in diverse cancers and propose an evolutionary model of repeat dynamics in cancer and normal tissues. Specifically, they highlight that properties of homorepeats contain sufficient information to discriminate healthy and tumour samples |
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