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10.1126/science.1222195 | 41,754,251 | Establishing an Enteric Infection Complex and highly regulated interactions are required to keep the peace between the bacteria that reside in our gut and the immune system. How do pathogenic bacteria, such as the strains of Escherichia coli that cause gastroenteritis, get a foothold to establish an infection, and what... | 10.1038/s41579-019-0252-z | This study shows that in C57BL/6 mice, following elimination of virulent C. rodentium , commensal bacteria are required to eradicate avirulent luminal C. rodentium |
10.1038/s41467-018-06701-4 | 102,287,023 | Abstract Niche-adaptation of a bacterial pathogen hinges on the ability to recognize the complexity of signals from the environment and integrate that information with the regulation of genes critical for infection. Here we report the transcriptome of the attaching and effacing pathogen Citrobacter rodentium during inf... | 10.1038/s41579-019-0252-z | This study shows that metabolism of microbiota-derived 1,2-propanediol by C. rodentium regulates virulence gene expression |
10.1136/gutjnl-2017-314195 | 102,115,136 | Objective In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 ( CARD9 ), a key innate immunity gene, is required to shape a normal gut microbiota. Card9 –/– mice are more susceptible to the enteric mouse pathoge... | 10.1038/s41579-019-0252-z | This study links an IBD susceptibility gene CARD9 , to increased sensitivity to enteric infection. Importantly, the implementation of an adequate diet can reverse the genetic susceptibility to infection |
10.1136/gutjnl-2018-316757 | 59,351,029 | Objective Loss of the Crohn’s disease predisposing NOD2 gene results in an intestinal microenvironment conducive for colonisation by attaching-and-effacing enteropathogens. However, it remains elusive whether it relies on the intracellular recruitment of the serine-threonine kinase RIPK2 by NOD2, a step that is require... | 10.1038/s41579-019-0252-z | This study demonstrates that clearance of C. rodentium is delayed in mice deficient in NOD2 and RIPK2 due to defective IL-17 responses and delayed recruitment of leukocytes |
10.1002/ange.201404953 | 82,000,351 | Abstract The photothermal conversion of CO 2 provides a straightforward and effective method for the highly efficient production of solar fuels with high solar‐light utilization efficiency. This is due to several crucial features of the Group VIII nanocatalysts, including effective energy utilization over the whole ran... | 10.1038/s41467-019-10996-2 | This paper is the first report on photothermal CO 2 conversion to CH 4 using supported metal nanoparticles |
10.1073/pnas.1508075112 | 20,690,520 | Natural photosynthesis harnesses solar energy to convert CO 2 and water to value-added chemical products for sustaining life. We present a hybrid bioinorganic approach to solar-to-chemical conversion in which sustainable electrical and/or solar input drives production of hydrogen from water splitting using biocompatibl... | 10.1038/s41467-019-10996-2 | First demonstration of the feasibility of hybrid bio/inorganic systems for light-driven CO 2 methanation using water as the hydrogen source |
10.1073/pnas.1414290111 | 20,372,102 | Significance For solar water splitting to be an economically viable resource, a 10% or higher solar-to-fuel conversion efficiency is required. Silicon photovoltaics (PV) are particularly attractive because silicon absorbs most of the solar spectrum, is nonprecious, and PV devices have dropped in price dramatically with... | 10.1038/s41467-019-10996-2 | Benchmark paper reporting high photon-to-fuel conversion efficiency using a photocatalytic system synthesized from earth-abundant elements |
10.1126/science.1181369 | 41,754,439 | Chromosomal Mapping The conformation of the genome in the nucleus and contacts between both proximal and distal loci influence gene expression. In order to map genomic contacts, Lieberman-Aiden et al. (p. 289 , see the cover) developed a technique to allow the detection of all interactions between genomic loci in the e... | 10.1038/s41587-023-01711-0 | This paper describes a powerful biochemical method for inferring cellular nanostructure. |
10.1093/brain/aws360 | 125,319,472 | Abstract Parkinson’s disease is a chronic progressive neurodegenerative disorder characterized by resting tremor, slowness of movements, rigidity, gait disturbance and postural instability. Most investigations on Parkinson’s disease focused on the basal ganglia, whereas the cerebellum has often been overlooked. However... | 10.1038/s41583-018-0002-7 | This article offers a comprehensive review of the role of the cerebellum in PD. |
10.1073/pnas.0502762102 | 124,961,185 | In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had t... | 10.1038/s41583-018-0002-7 | This fMRI study shows a similar time course of activation in the STN and the lateral cerebellum during sequence learning. |
10.1038/srep31378 | 122,846,463 | Abstract Humans can select actions by learning, planning, or retrieving motor memories. Reinforcement Learning (RL) associates these processes with three major classes of strategies for action selection: exploratory RL learns state-action values by exploration, model-based RL uses internal models to simulate future sta... | 10.1038/s41583-018-0002-7 | This fMRI study provides evidence that different learning strategies recruit distinct basal ganglia–cerebellum–cortical networks. |
10.1073/pnas.1507889112 | 20,421,556 | Carbon fluxes in subduction zones can be better constrained by including new estimates of carbon concentration in subducting mantle peridotites, consideration of carbonate solubility in aqueous fluid along subduction geotherms, and diapirism of carbon-bearing metasediments. Whereas previous studies concluded that about... | 10.1038/s41586-019-1643-z | This review summarizes carbon inputs and outputs to the mantle and emphasizes the potential for carbon to be efficiently recycled from the slab and potentially stored in the arc lithosphere |
10.1126/science.aan5049 | 83,013,965 | Volcanoes find a new carbon platform The geological carbon cycle assumes that carbon is emitted by volcanic eruptions and removed through various forms of burial. Mason et al. found that not all volcanic eruptions have the same source for carbon in their volcanic gas. Arc volcanic activity appears to harvest carbon fro... | 10.1038/s41586-019-1643-z | This paper reviews carbon isotopic compositions for volcanic gases globally and discusses crustal versus subducted sources of volcanic carbon and the implications for the carbon cycle |
10.1073/pnas.1620319114 | 20,832,986 | The human aspects of conservation are often overlooked but will be critical for identifying strategies for biological conservation in the face of climate change. We surveyed the behavioral intentions of coastal landowners with respect to various conservation strategies aimed at facilitating ecosystem migration for tida... | 10.1038/s41558-019-0488-7 | Landowner surveys indicate resistance to incentive programs allowing for marsh migration on private property |
10.1111/gcb.13398 | 40,964,032 | Abstract To thrive in a time of rapid sea‐level rise, tidal marshes will need to migrate upslope into adjacent uplands. Yet little is known about the mechanics of this process, especially in urbanized estuaries, where the adjacent upland is likely to be a mowed lawn rather than a wooded natural area. We studied marsh m... | 10.1038/s41558-019-0488-7 | Marsh vegetation develops rapidly in submerging suburban lawns and is not inhibited by mowing |
10.1002/fee.1282 | 125,269,921 | In the 21st century, accelerated sea‐level rise and continued coastal development are expected to greatly alter coastal landscapes across the globe. Historically, many coastal ecosystems have responded to sea‐level fluctuations via horizontal and vertical movement on the landscape. However, anthropogenic activities, in... | 10.1038/s41558-019-0488-7 | Large areas of land are available for migration on the Gulf Coast, but with large geographic variability due to anthropogenic and topographic barriers |
10.1073/pnas.94.11.5744 | 39,297,839 | The lymphocyte activation gene-3 (LAG-3), selectively transcribed in human activated T and NK cells, encodes a ligand for major histocompatibility complex (MHC) class II molecules. Like CD4, LAG-3 ectodomain is composed of four Ig-like domains (D1–D4). Nothing is known about the LAG-3 regions or residues required to fo... | 10.1038/s41590-022-01242-x | A mutational mapping study that defines the binding site of MHC class II molecules on the LAG3 protein |
10.4049/jimmunol.1900823 | 122,991,385 | Abstract T cells chronically stimulated with the same peptide tend to express exhaustion markers such as PD-1 or LAG-3. Deficiencies in the PD-1 and LAG-3 pathways have been linked to the development of autoimmune diseases. IMP761 is a LAG-3–specific humanized agonist Ab with immunosuppressive properties both in vitro ... | 10.1038/s41590-022-01242-x | This Article characterizes a LAG3 agonist antibody in a model of autoimmune disease |
10.1136/jitc-2020-001014 | 41,607,488 | To prevent the destruction of tissues owing to excessive and/or inappropriate immune responses, immune cells are under strict check by various regulatory mechanisms at multiple points. Inhibitory coreceptors, including programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), serve as critical check... | 10.1038/s41590-022-01242-x | A Review discussing the immunosuppressive mechanisms of LAG3 and its potential as a therapeutic target |
10.1038/s41598-017-09249-3 | 82,947,718 | Abstract Sex differences in the etiology of human trait variation are a major topic of interest in the social and medical sciences given its far-reaching implications. For example, in genetic research, the presence of sex-specific effects would require sex-stratified analysis, and in clinical practice sex-specific trea... | 10.1038/s41576-018-0083-1 | This meta-analysis of 2,335,920 twin pairs and over 2,600 phenotypes reports that only a small portion of human traits exhibit significant sex differences in heritability |
10.1534/genetics.116.193623 | 79,829,274 | Abstract Common diseases often show sex differences in prevalence, onset, symptomology, treatment, or prognosis. Although studies have been performed to evaluate sex differences at specific SNP associations, this work aims to comprehensively survey a number of complex heritable diseases and anthropometric traits. Poten... | 10.1038/s41576-018-0083-1 | This is one of the first studies to comprehensively evaluate multiple genetic models for evidence of their contribution to sex differences in several diseases and anthropometric traits |
10.1038/nature24265 | 62,618,791 | Abstract X chromosome inactivation (XCI) silences transcription from one of the two X chromosomes in female mammalian cells to balance expression dosage between XX females and XY males. XCI is, however, incomplete in humans: up to one-third of X-chromosomal genes are expressed from both the active and inactive X chromo... | 10.1038/s41576-018-0083-1 | This important study demonstrates that both escape from XCI and incomplete XCI, which affect a portion of ChrX genes, result in sex-biased gene expression across human tissues |
10.1038/ncomms3771 | 123,540,349 | Abstract There is strong evidence to show that men and women differ in terms of neurodevelopment, neurochemistry and susceptibility to neurodegenerative and neuropsychiatric disease. The molecular basis of these differences remains unclear. Progress in this field has been hampered by the lack of genome-wide information... | 10.1038/s41576-018-0083-1 | This study reports widespread sex-biased gene expression in 12 regions of the human brain |
10.3389/fnbeh.2022.845491 | 127,191,709 | Major depressive disorder (MDD) is amongst the most devastating psychiatric conditions affecting several millions of people worldwide every year. Despite the importance of this disease and its impact on modern societies, still very little is known about the etiological mechanisms. Treatment strategies have stagnated ov... | 10.1038/s41576-018-0083-1 | This study reports the remodelling of human brain transcriptional profiles in major depression, with little overlap in the alterations occurring in males and females |
10.1101/gr.197897.115 | 101,896,972 | The X Chromosome, with its unique mode of inheritance, contributes to differences between the sexes at a molecular level, including sex-specific gene expression and sex-specific impact of genetic variation. Improving our understanding of these differences offers to elucidate the molecular mechanisms underlying sex-spec... | 10.1038/s41576-018-0083-1 | This study characterizes human whole blood cis-eQTLs and SNP-by-sex interaction eQTLs on ChrX and autosomes and the relationship to sex-biased chromatin accessibility |
10.1128/mcb.00601-10 | 102,538,553 | ABSTRACT We have used a simple and efficient method to identify condition-specific transcriptional regulatory sites in vivo to help elucidate the molecular basis of sex-related differences in transcription, which are widespread in mammalian tissues and affect normal physiology, drug response, inflammation, and disease.... | 10.1038/s41576-018-0083-1 | This study characterizes sex-biased DNase occupancy in mouse liver associated with sex-biased gene expression and shows how chromatin accessibility can be altered by sex hormones |
10.1128/jvi.01774-19 | 61,964,779 | Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential an... | 10.1038/s41579-020-00468-6 | Highlights the requirements for cross-species transmission and the zoonotic potential of coronaviruses |
10.1128/jvi.01296-07 | 125,269,394 | ABSTRACT Replication fidelity of RNA virus genomes is constrained by the opposing necessities of generating sufficient diversity for adaptation and maintaining genetic stability, but it is unclear how the largest viral RNA genomes have evolved and are maintained under these constraints. A coronavirus (CoV) nonstructura... | 10.1038/s41579-020-00468-6 | Experimental evidence for the involvement of the nsp14 exonuclease activity in coronavirus genome integrity, which led, in subsequent studies, to the concept of an RNA proofreading function during coronavirus RNA synthesis |
10.1073/pnas.0808790106 | 20,675,801 | The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded ... | 10.1038/s41579-020-00468-6 | Discovery of N7 methyltransferase in SARS-CoV nsp14 as part of its RNA capping machinery |
10.1101/2020.06.23.167064 | 20,110,589 | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID19 pandemic, is a highly pathogenic β-coronavirus. As other coronaviruses, SARS-CoV-2 is enveloped, replicates in the cytoplasm and assembles at intracellular membranes. Here, we structurally characterize the viral replication... | 10.1038/s41579-020-00468-6 | Detailed ultrastructural investigation of the SARS-CoV-2 replication structures and assembly process, notably detecting viral (presumably double-stranded) RNA inside DMVs |
10.1128/jvi.76.8.3697-3708.2002 | 41,476,352 | ABSTRACT The replication complexes (RCs) of positive-stranded RNA viruses are intimately associated with cellular membranes. To investigate membrane alterations and to characterize the RC of mouse hepatitis virus (MHV), we performed biochemical and ultrastructural studies using MHV-infected cells. Biochemical fractiona... | 10.1038/s41579-020-00468-6 | First evidence that coronaviruses induce double-membrane structures in the cytoplasm of infected cells |
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/s41579-020-00468-6 | Identification of a pore connecting the interior of the coronavirus DMVs to the cytosol, thereby providing a plausible concept for how viral RNAs can exit DMVs |
10.1146/annurev-immunol-030409-101212 | 125,163,765 | CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T help... | 10.1038/s41590-022-01302-2 | A review article that presents the fundamentals of CD4 + T cells. |
10.1126/science.aax0194 | 20,426,994 | T cells maintain a quiescent state prior to activation. As inappropriate T cell activation can cause disease, T cell quiescence must be preserved. Despite its importance, the mechanisms underlying the “quiescent state” remain elusive. Here, we identify BTG1 and BTG2 (BTG1/2) as factors responsible for T cell quiescence... | 10.1038/s41590-022-01302-2 | This study demonstrates that the transcription factors BTG1 and BTG2 protect global mRNA polyadenylate tail length and T cell quiescence. |
10.1002/lpor.201600213 | 123,094,488 | Abstract Nanophotonic beamsplitters are fundamental building blocks in integrated optics, with applications ranging from high speed telecom receivers to biological sensors and quantum splitters. While high‐performance multiport beamsplitters have been demonstrated in several material platforms using multimode interfere... | 10.1038/s41586-018-0421-7 | This study exploited the anisotropy of SWG structures to achieve broadband operation |
10.12688/f1000research.13440.1 | 123,384,305 | In the August 16th issue of Science Translational Medicine, Phallen et al propose a method for early cancer diagnosis by using circulating tumor DNA (1). One major advance of this paper includes optimized sequencing of cell-free/circulating tumor DNA (ctDNA) without knowledge of tumor mutations. Evaluation of 200 patie... | 10.1038/s41576-018-0071-5 | In this study, high-resolution gene panel profiling (TEC-Seq) is employed for non-invasive detection of early-stage tumours in 200 patients with stage I or II colorectal, breast, lung or ovarian cancer |
10.1073/pnas.1804134115 | 83,338,470 | Cell-free DNA in human plasma is nonrandomly fragmented and reflects genomewide nucleosomal organization. Previous studies had demonstrated tissue-specific preferred end sites in plasma DNA of pregnant women. In this study, we performed integrative analysis of preferred end sites with the size characteristics of plasma... | 10.1038/s41576-018-0071-5 | The authors investigate whether preferred end sites might bear any relationship with fragment lengths of plasma DNA. Short and long plasma DNA molecules were associated with different preferred DNA end sites |
10.1073/pnas.1508736112 | 29,286,493 | Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA and deconvolution of the sequencing data with reference to methylation profiles of different tissues, we developed a general approach for studying the major tissue contributors to the circulating ... | 10.1038/s41576-018-0071-5 | In this study, the tissue of origin of circulating cell-free DNA is tracked using methylation deconvolution in different cohorts |
10.3389/fspas.2021.797591 | 127,507,512 | Salar de Pajonales, a Ca-sulfate salt flat in the Chilean High Andes, showcases the type of polyextreme environment recognized as one of the best terrestrial analogs for early Mars because of its aridity, high solar irradiance, salinity, and oxidation. The surface of the salar represents a natural climate-transition ex... | 10.1038/s41550-023-01894-1 | An article that presents observations on the origins of salt structures in the SdP. |
10.3389/fmicb.2020.561427 | 58,772,096 | Microbes encompass tremendous biodiversity, provide support to all living forms, including humans, and play an important role in many ecosystem services. The rules that govern microorganism community assembly are increasingly revealed due to key advances in molecular and analytical methods but their understanding remai... | 10.1038/s41550-023-01894-1 | A review article that presents the main concepts, current applications and future directions in microbial landscape ecology |
10.1126/science.1177319 | 125,224,198 | Thalidomide Teratogenicity Target In the late 1950s and early 1960s, thalidomide was prescribed to pregnant women as a cure for morning sickness, but it was then found to have developmental defects, most obviously, stunted limbs in thousands of babies. Although its use was banned worldwide, thalidomide has since been f... | 10.1038/s41573-022-00409-3 | This paper reports how chemoproteomics enabled the discovery that thalidomide binds to an E3 ligase complex |
10.1073/pnas.96.26.14694 | 20,515,027 | With the postgenome era rapidly approaching, new strategies for the functional analysis of proteins are needed. To date, proteomics efforts have primarily been confined to recording variations in protein level rather than activity. The ability to profile classes of proteins on the basis of changes in their activity wou... | 10.1038/s41573-022-00409-3 | This article is a landmark study that introduces activity-based protein profiling |
10.1126/science.aab1433 | 104,262,163 | A degrading game plan for cancer therapy Certain classes of proteins that contribute to cancer development are challenging to target therapeutically. Winter et al. devised a chemical strategy that, in principle, permits the selective degradation of any protein of interest. The strategy involves chemically attaching a l... | 10.1038/s41573-022-00409-3 | The above two articles relate to breakthrough studies that sparked renewed interest in targeted degradation as therapeutic strategy |
10.1261/rna.035667.112 | 125,063,670 | Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-d... | 10.1038/s41580-020-0243-y | This study uncovers circRNAs as a large class of RNA molecules in human cells |
10.1101/gr.202895.115 | 103,689,138 | Circular RNAs (circRNAs) derived from back-spliced exons have been widely identified as being co-expressed with their linear counterparts. A single gene locus can produce multiple circRNAs through alternative back-splice site selection and/or alternative splice site selection; however, a detailed map of alternative bac... | 10.1038/s41580-020-0243-y | This study defines the diversity of alternative back-splicing and alternative splicing in circRNAs |
10.1101/gad.314856.118 | 29,113,296 | Circular RNAs (circRNAs) are generated from many protein-coding genes. Most accumulate in the cytoplasm, but how circRNA localization or nuclear export is controlled remains unclear. Using RNAi screening, we found that depletion of the Drosophila DExH/D-box helicase Hel25E results in nuclear accumulation of long (>8... | 10.1038/s41580-020-0243-y | This study reveals that circRNA nuclear export occurs in a length-dependent manner |
10.1126/science.284.5411.143 | 41,739,425 | Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the charac... | 10.1038/s41580-020-00279-w | This work establishes the potential for MSCs to differentiate into bone, cartilage and fat |
10.1038/ncomms10928 | 18,943,440 | Abstract Immune responses are crucial not only for host defence against pathogens but also for tissue maintenance and repair after injury. Lymphocytes are involved in the healing process after tissue injury, including bone fracture and muscle damage. However, the specific immune cell subsets and mediators of healing ar... | 10.1038/s41580-020-00279-w | This work shows that the presence of the proinflammatory cytokine IL-17, from the niche, aided in bone regrowth after injury |
10.1073/pnas.0701600104 | 103,767,521 | Fibroblast growth factor 21 (FGF21) is a liver-derived endocrine factor that stimulates glucose uptake in adipocytes. Here, we show that FGF21 activity depends on βKlotho, a single-pass transmembrane protein whose expression is induced during differentiation from preadipocytes to adipocytes. βKlotho physically interact... | 10.1038/s41581-018-0078-3 | This study demonstrates that βKlotho forms complexes with FGFR1c and functions as the obligate co-receptor for FGF21 |
10.1126/science.1112766 | 20,626,217 | A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insu... | 10.1038/s41581-018-0078-3 | This study confirmed that the αKlotho gene is an ageing-suppressor gene that can extend lifespan when overexpressed |
10.1128/mmbr.00020-10 | 83,444,609 | SUMMARY Plasmids are key vectors of horizontal gene transfer and essential genetic engineering tools. They code for genes involved in many aspects of microbial biology, including detoxication, virulence, ecological interactions, and antibiotic resistance. While many studies have decorticated the mechanisms of mobility ... | 10.1038/s41579-020-00497-1 | A thorough analysis of plasmid mobility that sets the basis for mobility typing |
10.1038/s41467-020-16282-w | 79,804,826 | Abstract Many bacteria can exchange genetic material through horizontal gene transfer (HGT) mediated by plasmids and plasmid-borne transposable elements. Here, we study the population structure and dynamics of over 10,000 bacterial plasmids, by quantifying their genetic similarities and reconstructing a network based o... | 10.1038/s41579-020-00497-1 | A comprehensive analysis of plasmid whole-genome sequences using similarity networks that paves the way for novel plasmid classification schemes |
10.1073/pnas.1514326112 | 82,905,878 | rRNA is essential for life because of its functional importance in protein synthesis. The rRNA ( rrn ) operon encoding 16S, 23S, and 5S rRNAs is located on the “main” chromosome in all bacteria documented to date and is frequently used as a marker of chromosomes. Here, our genome analysis of a plant-associated alphapro... | 10.1038/s41579-020-00497-1 | An example of an HCP carrying an essential core gene for its bacterial host |
10.1038/s41467-019-13709-x | 40,578,735 | Abstract Transmissible plasmids spread genes encoding antibiotic resistance and other traits to new bacterial species. Here we report that laboratory populations of Escherichia coli with a newly acquired IncQ plasmid often evolve ‘satellite plasmids’ with deletions of accessory genes and genes required for plasmid repl... | 10.1038/s41579-020-00497-1 | An elegant study highlighting the role of recombination in plasmid evolution |
10.1111/mec.14056 | 107,389,530 | Abstract Plasmids are nucleic acid molecules that can drive their own replication in a living cell. They can be transmitted horizontally and can thrive in the host cell to high‐copy numbers. Plasmid replication and gene expression consume cellular resources and cells carrying plasmids incur fitness costs. But many plas... | 10.1038/s41579-020-00497-1 | A study describing for the first time the effects of plasmid interference in evolving bacterial populations |
10.1073/pnas.2001240117 | 101,152,067 | Mobile genetic elements (MGEs), such as plasmids, promote bacterial evolution through horizontal gene transfer (HGT). However, the rules governing the repertoire of traits encoded on MGEs remain unclear. In this study, we uncovered the central role of genetic dominance shaping genetic cargo in MGEs, using antibiotic re... | 10.1038/s41579-020-00497-1 | The first article to demonstrate that genetic dominance shapes plasmid evolution and genetic content |
10.1038/ncomms13989 | 20,485,317 | Abstract Extracellular matrix adhesion is required for normal epithelial cell survival, nutrient uptake and metabolism. This requirement can be overcome by oncogene activation. Interestingly, inhibition of PI3K/mTOR leads to apoptosis of matrix-detached, but not matrix-attached cancer cells, suggesting that matrix-atta... | 10.1038/s41568-018-0048-x | This study shows that dietary restriction and nutrient deprivation promote laminin scavenging via α6β4 integrin-mediated endocytosis. Endocytosed laminin maintains essential amino acid levels and supports growth and proliferation when serum and growth factors or nutrients are limited |
10.1126/science.aan6298 | 61,552,945 | The lysosome degrades and recycles macromolecules, signals to the cytosol and nucleus, and is implicated in many diseases. Here, we describe a method for the rapid isolation of mammalian lysosomes and use it to quantitatively profile lysosomal metabolites under various cell states. Under nutrient-replete conditions, ma... | 10.1038/s41568-018-0048-x | This study shows that mTORC1 activity is necessary for the efflux of hydrophobic essential amino acids from the lysosome. This study identified signalling pathways regulating lysosomal nutrient efflux |
10.1126/scisignal.2004754 | 62,022,351 | Enhancing TFE3 activity to promote expression of lysosome-associated genes may be beneficial in treating lysosomal storage disorders. | 10.1038/s41568-018-0048-x | This study shows that TFE3 promotes lysosomal biogenesis and autophagy by increasing the expression of coordinated lysosomal expression and regulation (CLEAR) network genes. mTORC1 inactivation and nutrient stress promote lysosomal biogenesis and function by driving the nuclear translocation of TFE3 |
10.1126/scisignal.2002790 | 62,542,322 | The nuclear translocation of a transcription factor that promotes lysosomal biogenesis is inhibited when lysosomal function is adequate. | 10.1038/s41568-018-0048-x | This study shows that TFEB promotes lysosomal biogenesis and autophagy by increasing the expression of CLEAR network genes. mTORC1 inactivation and nutrient stress promote lysosomal biogenesis and function by driving the nuclear translocation of TFEB. |
10.1101/gad.2016111 | 62,113,269 | Macroautophagy (autophagy) is a regulated catabolic pathway to degrade cellular organelles and macromolecules. The role of autophagy in cancer is complex and may differ depending on tumor type or context. Here we show that pancreatic cancers have a distinct dependence on autophagy. Pancreatic cancer primary tumors and ... | 10.1038/s41575-021-00431-7 | This study provides the first evidence demonstrating that PDAC tumour cells depend on autophagy to support tumour growth |
10.1126/science.aao4908 | 103,409,467 | The majority of patients with pancreatic ductal adenocarcinoma (PDA) develop metastatic disease after resection of their primary tumor. We found that livers from patients and mice with PDA harbor single disseminated cancer cells (DCCs) lacking expression of cytokeratin 19 (CK19) and major histocompatibility complex cla... | 10.1038/s41575-021-00431-7 | In patients with PDAC and mouse models, disseminated cancer cells lack the cytokeratin 19-negative (CK19) and major histocompatibility complex class I (MHC-I) |
10.1073/pnas.1817494116 | 19,994,193 | Oncogenic mutations in the small GTPase KRAS are frequently found in human cancers, and, currently, there are no effective targeted therapies for these tumors. Using a combinatorial siRNA approach, we analyzed a panel of KRAS mutant colorectal and pancreatic cancer cell lines for their dependency on 28 gene nodes that ... | 10.1038/s41575-021-00431-7 | Together with Bryant et al. (2019) and Kinsey et al. (2019), this study shows that a combination of chloroquine and MEK/ERK inhibition is a novel therapeutic approach for PDAC and KRAS-mutant cancers. |
10.1038/s41586-020-1943-3 | 83,488,365 | Abstract Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1 . Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCG... | 10.1038/s41568-021-00377-7 | This study reports the largest number of mutational signatures to date, which form the basis of COSMIC mutational signatures v3, and introduces DBSs and IDs |
10.1126/science.1143422 | 29,187,631 | During cytokinesis, as dividing animal cells pull apart into two daughter cells, the final stage, termed abscission, requires breakage of the midbody, a thin membranous stalk connecting the daughter cells. This membrane fission event topologically resembles the budding of viruses, such as HIV-1, from infected cells. We... | 10.1038/s41580-019-0177-4 | First demonstration that ESCRTs mediate cytokinetic abscission, and that TSG101 and ALIX are recruited to the midbody ring by binding CEP55 |
10.1126/science.1217180 | 59,313,837 | To Cut or Not to Cut During animal cell division, the final separation of daughter cells requires ESCRT-III (endosomal sorting complex required for transport III), the core membrane scission machinery. Carlton et al. (p. 220 , published online 15 March; see the Perspective by Petronczki and Uhlmann ) report that ESCRT-... | 10.1038/s41580-019-0177-4 | This study provided a mechanistic link between the abscission checkpoint and the ESCRT machinery via the ESCRT-III component CHMP4C, which contains a phosphorylation site for Aurora B |
10.1038/srep08461 | 124,264,206 | Abstract Neural circuits are refined by both functional and structural changes. Structural remodeling by large-scale pruning occurs where relatively long neuronal branches are cut away from their parent neuron and removed by local degeneration. Until now, the molecular mechanisms executing such branch severing events h... | 10.1038/s41580-019-0177-4 | Together with Zhang et al 67 , this paper demonstrated that ESCRTs mediate neuronal pruning. This paper proposes a non-endocytic mechanism that acts directly on the plasma membrane |
10.1126/science.1247136 | 104,089,072 | ESCRT Your Wound Away The ESCRT (endosomal sorting complex required for transport) protein complex plays a role in budding into multivesicular bodies, in cytokinesis, and in HIV budding. Now, Jimenez et al. (p. 10.1126/science.1247136 , published online 30 January) propose a role for ESCRT proteins in wound repair at t... | 10.1038/s41580-019-0177-4 | Demonstration that ESCRT-III is required for repair of small wounds in the plasma membrane, and that extracellular buds are found at the site of ESCRT-III recruitment |
10.1126/science.aad7611 | 83,024,030 | Repairing tears in the nuclear envelope The nuclear envelope segregates genomic DNA from the cytoplasm and regulates protein trafficking between the cytosol and the nucleus. Maintaining nuclear envelope integrity during interphase is considered crucial. However, Raab et al. and Denais et al. show that migrating immune ... | 10.1038/s41580-019-0177-4 | Together with Denais et al. (ref. 90), this paper demonstrated that ESCRT-III repairs ruptures in the nuclear envelope during cell migration through confined spaces |
10.1038/s41467-018-05889-9 | 39,334,309 | Abstract Vesicle-mediated nucleocytoplasmic transport is a nuclear pore-independent mechanism for the nuclear export of macromolecular complexes, but the molecular basis for this transport remains largely unknown. Here we show that endosomal sorting complex required for transport-III (ESCRT-III) is recruited to the inn... | 10.1038/s41580-019-0177-4 | Demonstration that ESCRT-III mediates budding of HSV-1 across the inner nuclear membrane, and that ESCRT-III-mediated budding of the inner nuclear membrane in non-infected cells plays a role in nuclear envelope homeostasis |
10.1126/science.aar5078 | 83,540,309 | Endolysosomes can be damaged by diverse materials. Terminally damaged compartments are degraded by lysophagy, but pathways that repair salvageable organelles are poorly understood. Here we found that the endosomal sorting complex required for transport (ESCRT) machinery, known to mediate budding and fission on endolyso... | 10.1038/s41580-019-0177-4 | First demonstration that ESCRTs promote sealing of damaged lysosomes, and identification of Ca 2+ and ALG2 as triggers of ESCRT recruitment to the sites of membrane damage |
10.1200/jco.2010.29.7101 | 62,151,321 | Purpose This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases. Patients and Methods Patients were random... | 10.1038/s41572-020-00216-3 | This study is the first RCT to demonstrate the role of denosumab in patients with bone metastases and superior efficacy compared with a bisphosphonate |
10.1126/science.abc1669 | 41,721,557 | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission through the respiratory route. However, clinical evidence suggests that the intestine may present another viral target org... | 10.1038/s41574-020-00462-1 | This important study reports that SARS-CoV and SARS-CoV-2 readily infect enterocytes |
10.1038/s41592-021-01358-2 | 128,850,692 | Abstract Spatial omics data are advancing the study of tissue organization and cellular communication at an unprecedented scale. Flexible tools are required to store, integrate and visualize the large diversity of spatial omics data. Here, we present Squidpy, a Python framework that brings together tools from omics and... | 10.1038/s41592-023-01772-8 | This paper describes Squidpy, one of the most useful spatial omics analysis packages. |
10.1038/s41592-021-01336-8 | 128,113,885 | Abstract Single-cell atlases often include samples that span locations, laboratories and conditions, leading to complex, nested batch effects in data. Thus, joint analysis of atlas datasets requires reliable data integration. To guide integration method choice, we benchmarked 68 method and preprocessing combinations on... | 10.1038/s41592-023-01772-8 | This paper surveys and benchmarks many computational methods for single-cell data integration. |
10.1002/yea.3242 | 62,621,157 | Abstract Hybridization between different species can result in the emergence of new lineages and adaptive phenotypes. Occasionally, hybridization in fungal organisms can drive the appearance of opportunistic lifestyles or shifts to new hosts, resulting in the emergence of novel pathogens. In recent years, an increasing... | 10.1038/s41579-021-00537-4 | In this review, the authors comprehensively discuss how hybridization can influence the origin and evolution of pathogenic fungal lineages |
10.1073/pnas.1201403109 | 104,412,832 | In a genome alignment of five individuals of the ascomycete fungus Zymoseptoria pseudotritici , a close relative of the wheat pathogen Z. tritici (synonym Mycosphaerella graminicola ), we observed peculiar diversity patterns. Long regions up to 100 kb without variation alternate with similarly long regions of high vari... | 10.1038/s41579-021-00537-4 | This article describes one of the few cases of homoploid speciation discovered in fungi to date |
10.1126/science.1169766 | 62,643,770 | Gene Expression in Hybrids A large proportion of genes differ in their expression patterns between closely related species, and this divergence is believed to be an important driver of phenotypic evolution. However, little is known about the genetic basis of this divergence. Tirosh et al. (p. 659 ) use allele-specific ... | 10.1038/s41579-021-00537-4 | In this article, the authors map the contribution of cis and trans polymorphisms to expression variation in an interspecific yeast hybrid |
10.1101/gr.197244.115 | 58,984,001 | Genome evolution is driven by a complex interplay of factors, including selection, recombination, and introgression. The regions determining sexual identity are particularly dynamic parts of eukaryotic genomes that are prone to molecular degeneration associated with suppressed recombination. In the fungus Neurospora te... | 10.1038/s41579-021-00537-4 | By investigating 92 Neurospora genomes, the authors identify many cases of adaptive introgressions in the mat locus |
10.1126/science.abc8697 | 104,378,503 | TP53 (tumor protein p53) is the most commonly mutated cancer driver gene, but drugs that target mutant tumor suppressor genes, such as TP53 , are not yet available. Here, we describe the identification of an antibody highly specific to the most common TP53 mutation (R175H, in which arginine at position 175 is replaced ... | 10.1038/s41573-022-00571-8 | This paper reports a bispecific antibody, highly specific to the p53(R175H) mutation, which activates T cells to kill cancer cells presenting a p53(R175H)-derived neoantigen in vitro and in vivo |
10.1126/scitranslmed.aaw1565 | 62,287,783 | Loss of function in tumor suppressor genes is commonly associated with the onset/progression of cancer and treatment resistance. The p53 tumor suppressor gene, a master regulator of diverse cellular pathways, is frequently altered in various cancers, for example, in ~36% of hepatocellular carcinomas (HCCs) and ~68% of ... | 10.1038/s41573-022-00571-8 | This paper describes the use of synthetic p53 mRNA as a potential anticancer treatment |
10.1126/science.1104904 | 19,037,328 | CD4 + T cells classically recognize antigens that are endocytosed and processed in lysosomes for presentation on major histocompatibility complex (MHC) class II molecules. Here, endogenous Epstein-Barr virus nuclear antigen 1 (EBNA1) was found to gain access to this pathway by autophagy. On inhibition of lysosomal acid... | 10.1038/s41579-018-0003-6 | In this study, autophagy-mediated lysosomal processing contributes to MHC class II-restricted surveillance of EBV to generate EBNA1-specific CD4+ T cells. |
10.1126/science.1136880 | 20,587,005 | Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytos... | 10.1038/s41579-018-0003-6 | This study reveals that autophagy occurs in pDCs and is required for recognition of viral infection and production of type I IFNs, highlighting the importance of autophagy in innate immunity against viral pathogenesis. |
10.1128/jvi.72.11.8586-8596.1998 | 81,637,451 | ABSTRACT bcl-2 , the prototypic cellular antiapoptotic gene, decreases Sindbis virus replication and Sindbis virus-induced apoptosis in mouse brains, resulting in protection against lethal encephalitis. To investigate potential mechanisms by which Bcl-2 protects against central nervous system Sindbis virus infection, w... | 10.1038/s41579-018-0003-6 | This study is the first to identify one of the most important mammalian autophagy proteins, Beclin 1, as a BCL-2-binding protein upon viral infection. |
10.1126/science.1246829 | 105,313,440 | The Secret Life of a Vaccine Antigen-specific CD8 ÷ T cells play a central role in the adaptive immune response to viral infections and to cancer. Ravindran et al. (p. 313 , published online 5 December) studied the successful yellow fever virus vaccine YF-17D to gain insight into its mechanism of action. The vaccine ac... | 10.1038/s41579-018-0003-6 | In this study, an unknown mechanism of vaccine-mediated protection reveals that stress-response dependent initiation of autophagy enhances antigen presentation to T cells. |
10.1159/000452082 | 103,663,253 | Bloom's syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early onset of cancer and for the development of multiple cancers. Loss-of-function mutations of <i>BLM... | 10.1038/s41572-019-0113-0 | A comprehensive paper that discusses the features of BS and its underlying molecular pathology |
10.1111/cge.12517 | 20,724,693 | Fanconi anaemia ( FA ) is an inherited disease with congenital and developmental abnormalities, cross‐linker hypersensitivity and extreme cancer predisposition. With better understanding of the genetic and molecular basis of the disease, and improved clinical management, FA has been transformed from a life‐limiting pae... | 10.1038/s41572-019-0113-0 | This paper describes the clinical management of patients with FA |
10.1002/ppul.22760 | 41,010,158 | Abstract Background Pulmonary disease contributes to significant morbidity and mortality in people with ataxia telangiectasia (A‐T). To determine the association between age and lung function in children and young adults with A‐T and to identify factors associated with decreased lung function, pulmonary function tests ... | 10.1038/s41572-019-0113-0 | This paper reports the incidence of an important clinical feature (pulmonary function) in children and young adults with classic A-T |
10.1002/ajmg.a.40374 | 62,014,604 | Bloom Syndrome (BSyn) is an autosomal recessive disorder that causes growth deficiency, endocrine abnormalities, photosensitive skin rash, immune abnormalities, and predisposition to early‐onset cancer. The available treatments for BSyn are symptomatic, and early identification of complications has the potential to imp... | 10.1038/s41572-019-0113-0 | This paper offers recommendations for diagnosis, screening and symptom treatment in BS |
10.1038/s41467-018-03367-w | 125,209,222 | Abstract Nanoscale or single-cell technologies are critical for biomedical applications. However, current mass spectrometry (MS)-based proteomic approaches require samples comprising a minimum of thousands of cells to provide in-depth profiling. Here, we report the development of a nanoPOTS (nanodroplet processing in o... | 10.1038/s41592-023-01785-3 | Introduced a microfabricated chip (nanoPOTS) for sample preparation and used it to prepare small bulk samples in sample volumes of about 200 nl |
10.1186/s13059-022-02817-5 | 139,440,112 | Abstract Background Many biological processes, such as cell division cycle and drug resistance, are reflected in protein covariation across single cells. This covariation can be quantified and interpreted by single-cell mass spectrometry with sufficiently high throughput and accuracy. Results Here, we describe nPOP, a ... | 10.1038/s41592-023-01785-3 | Introduced a method for simultaneous sample preparation of thousands of single cells in droplets of about 20 nl on the surface of glass slides. It also demonstrated cross-validation based on using different MS methods |
10.1002/anie.202100923 | 124,502,525 | Abstract We report the development of in vivo subcellular high‐resolution mass spectrometry (HRMS) for proteo‐metabolomic molecular systems biology in complex tissues. With light microscopy, we identified the left‐dorsal and left‐ventral animal cells in cleavage‐stage non‐sentient Xenopus laevis embryos. Using precisio... | 10.1038/s41592-023-01785-3 | This study used in vivo and dual proteo-metabolomics single-cell MS for single-cell molecular systems biology in live vertebrate embryos |
10.1038/s41467-021-23667-y | 135,560,152 | Abstract Large-scale single-cell analyses are of fundamental importance in order to capture biological heterogeneity within complex cell systems, but have largely been limited to RNA-based technologies. Here we present a comprehensive benchmarked experimental and computational workflow, which establishes global single-... | 10.1038/s41592-023-01785-3 | Analyzed primary cells using an isobaric carrier and modified SCoPE2 approach |
10.1186/s13059-021-02267-5 | 38,437,486 | Abstract Background Macrophages are innate immune cells with diverse functional and molecular phenotypes. This diversity is largely unexplored at the level of single-cell proteomes because of the limitations of quantitative single-cell protein analysis. Results To overcome this limitation, we develop SCoPE2, which subs... | 10.1038/s41592-023-01785-3 | This study analyzed thousands of proteins in over a thousand single cells. It performed parallel RNA and protein measurements in single cells and identified the emergence of polarization in the absence of polarizing cytokines |
10.1101/2022.03.16.484655 | 135,891,157 | Major aims of single-cell proteomics include increasing the consistency, sensitivity, and depth of protein quantification, especially for proteins and modifications of biological interest. To simultaneously advance all of these aims, we developed prioritized Single Cell ProtEomics (pSCoPE). pSCoPE ensures duty-cycle ti... | 10.1038/s41592-023-01785-3 | Demonstrated that prioritized MS analysis increases the consistency, sensitivity and depth of protein quantification in single cells. It also enabled quantifying post-translational modifications and polarization in primary macrophages |
10.1101/399774 | 41,095,186 | A major limitation to applying quantitative LC-MS/MS proteomics to small samples, such as single cells, are the losses incured during sample cleanup. To relieve this limitation, we developed a Minimal ProteOmic sample Preparation (mPOP) method for culture-grown mammalian cells. mPOP obviates cleanup and thus eliminates... | 10.1038/s41592-023-01785-3 | An automated method for simultaneously preparing hundreds of single cells for MS analysis |
10.1002/anie.201802843 | 102,632,714 | Abstract We report on the quantitative proteomic analysis of single mammalian cells. Fluorescence‐activated cell sorting was employed to deposit cells into a newly developed nanodroplet sample processing chip, after which samples were analyzed by ultrasensitive nanoLC‐MS. An average of circa 670 protein groups were con... | 10.1038/s41592-023-01785-3 | A label-free MS analysis of hundreds of proteins in single HeLa cells |
10.1126/science.aav2588 | 104,407,712 | The metabolic characteristics of tumors present considerable hurdles to immune cell function and cancer immunotherapy. Using a glutamine antagonist, we metabolically dismantled the immunosuppressive microenvironment of tumors. We demonstrate that glutamine blockade in tumor-bearing mice suppresses oxidative and glycoly... | 10.1038/s41568-020-0273-y | This study demonstrates, using pharmacologic glutamine blockade, the potential of leveraging the ability of CD8 + T cells to use alternative metabolic pathways, including acetate metabolism and glucose anaplerosis, to enhance the antitumour response |
10.1084/jem.189.9.1363 | 20,783,585 | We have recently shown that expression of the enzyme indoleamine 2,3-dioxygenase (IDO) during murine pregnancy is required to prevent rejection of the allogeneic fetus by maternal T cells. In addition to their role in pregnancy, IDO-expressing cells are widely distributed in primary and secondary lymphoid organs. Here ... | 10.1038/s41568-020-0273-y | This paper uncovers the ability of macrophages to induce cell cycle arrest in T eff cells through the IDO-dependent catabolism of tryptophan |
10.1073/pnas.0605251103 | 29,257,253 | The A2A adenosine receptor (A2AR) has been shown to be a critical and nonredundant negative regulator of immune cells in protecting normal tissues from inflammatory damage. We hypothesized that A2AR also protects cancerous tissues by inhibiting incoming antitumor T lymphocytes. Here we confirm this hypothesis by showin... | 10.1038/s41568-020-0273-y | This study demonstrates that pharmacologic or genetic inhibition of adenosine-A2AR receptor signalling on T cells enhanced T cell-mediated tumour regression and destruction of metastases |
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