source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.5194/bg-10-7793-2013 | 83,405,415 | Abstract. The Atlantic Ocean is one of the most important sinks for atmospheric carbon dioxide (CO2), but this sink has been shown to vary substantially in time. Here we use surface ocean CO2 observations to estimate this sink and the temporal variability from 1998 through 2007 in the Atlantic Ocean. We benefit from (i... | 10.1038/s41586-019-0912-1 | This paper describes the first data-driven machine-learning-based carbon fluxes in the ocean |
10.5194/isprs-archives-xlii-1-w1-551-2017 | 122,385,624 | Abstract. Land cover classification (LCC) is a central and wide field of research in earth observation and has already put forth a variety of classification techniques. Many approaches are based on classification techniques considering observation at certain points in time. However, some land cover classes, such as cro... | 10.1038/s41586-019-0912-1 | This paper describes the first use of the LSTM deep learning model for multi-temporal land-cover classification |
10.1073/pnas.1514074113 | 19,212,407 | Midbrain dopamine neurons project densely to the striatum and form so-called dopamine synapses on medium spiny neurons (MSNs), principal neurons in the striatum. Because dopamine receptors are widely expressed away from dopamine synapses, it remains unclear how dopamine synapses are involved in dopaminergic transmissio... | 10.1038/s41583-021-00455-7 | Dopamine axons can make synaptic contacts with MSNs but dopamine receptors seem to be excluded from the postsynaptic areas |
10.1126/sciadv.aaw3108 | 20,842,955 | Neuromodulation plays a critical role in brain function in both health and disease, and new tools that capture neuromodulation with high spatial and temporal resolution are needed. Here, we introduce a synthetic catecholamine nanosensor with fluorescent emission in the near infrared range (1000–1300 nm), near infrared ... | 10.1038/s41583-021-00455-7 | The generation and use of improved nanotube dopamine sensors reveal that striatal dopamine release occurs at small, sparse hotspots |
10.7554/elife.58359 | 121,431,174 | Dopamine powerfully controls neural circuits through neuromodulation. In the vertebrate striatum, dopamine adjusts cellular functions to regulate behaviors across broad time scales, but how the dopamine secretory system is built to support fast and slow neuromodulation is not known. Here, we set out to identify Ca2+-tr... | 10.1038/s41583-021-00455-7 | Synaptotagmin 1 is the main fast Ca 2+ sensor for synchronous dopamine release in the striatum, and supplementary Ca 2+ sensors may mediate additional release modes |
10.1126/science.aav2334 | 83,035,127 | Bulk–surface correspondence in Weyl semimetals ensures the formation of topological “Fermi arc” surface bands whose existence is guaranteed by bulk Weyl nodes. By investigating three distinct surface terminations of the ferromagnetic semimetal Co 3 Sn 2 S 2 , we verify spectroscopically its classification as a time-rev... | 10.1038/s41586-022-05516-0 | Quasiparticle scattering of the surface Fermi arc states in a kagome magnet |
10.1126/scitranslmed.aad3740 | 62,311,561 | Antioxidants increase migration and invasion of human melanoma cells and accelerate metastasis in an endogenous mouse model of malignant melanoma. | 10.1038/s41568-020-00320-2 | This article provides evidence that antioxidants and the glutathione synthesis can increase lymph node metastasis formation of melanoma |
10.1126/science.aan8690 | 103,781,606 | Brain mutations, young and old Most neurons that make up the human brain are postmitotic, living and functioning for a very long time without renewal (see the Perspective by Lee). Bae et al. examined the genomes of single neurons from the prenatal developing human brain. Both the type of mutation and the rates of accum... | 10.1038/s41593-018-0257-3 | This study used clonal cell expansion of fetal human neuronal progenitor cells to estimate the somatic mutation rate during neurogenesis |
10.1126/science.aao4426 | 62,160,543 | Brain mutations, young and old Most neurons that make up the human brain are postmitotic, living and functioning for a very long time without renewal (see the Perspective by Lee). Bae et al. examined the genomes of single neurons from the prenatal developing human brain. Both the type of mutation and the rates of accum... | 10.1038/s41593-018-0257-3 | This study used whole-genome sequencing of single human neurons to demonstrate that somatic SNVs in human neurons accumulate linearly with age |
10.1126/science.aab1785 | 62,312,248 | Neurons live for decades in a postmitotic state, their genomes susceptible to DNA damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs) in the human brain. We identified thousands of somatic SNVs by single-cell sequencing of 36 neurons from the cerebral cortex of three normal individuals. Un... | 10.1038/s41593-018-0257-3 | This study used whole-genome sequencing of single human neurons to estimate the number of somatic mutations in each postmitotic neuron |
10.1126/science.1243472 | 103,786,433 | Not All Neurons Are Alike As life proceeds, many cells acquire individualized mutations. In the immune system, genome rearrangements generate useful antibody diversity. McConnell et al. (p. 632 ; see the Perspective by Macosko and McCarroll ) now show that human neurons also diversify. Neurons taken from postmortem hum... | 10.1038/s41593-018-0257-3 | This study demonstrated that mosaic CNVs are common in human neurons |
10.1002/bdra.23067 | 103,774,413 | Abstract BACKGROUND: The prevalence of esophageal atresia (EA) has been shown to vary across different geographical settings. Investigation of geographical differences may provide an insight into the underlying etiology of EA. METHODS: The study population comprised infants diagnosed with EA during 1998 to 2007 from 18... | 10.1038/s41572-019-0077-0 | This study, together with that of Pedersen et al. (2012), reports the prevalence of EA with or without TEF and its associated anomalies as calculated from national and international databases for congenital anomalies and reports the number of spontaneous intrauterine deaths and induced abortions |
10.1055/s-0036-1597946 | 41,513,076 | Background Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) represents the most common developmental malformation of the upper digestive tract. It is classified into six subtypes according to the classification of Vogt, depending on anatomical variation of this malformation. Around 50% of the patie... | 10.1038/s41572-019-0077-0 | This study is the first to specifically look at different EA subtypes and co-occurring congenital anomalies |
10.1126/science.aao6047 | 19,064,964 | The great escape Mitochondrial DNA (mtDNA) is a potent damage-associated molecular pattern that, if it reaches the cytoplasm or extracellular milieu, triggers innate immune pathways. mtDNA signaling has been implicated in a wide range of diseases; however, the mechanisms of mtDNA release are unclear, and the process ha... | 10.1038/s41580-022-00564-w | This study revealed that BAX/BAK can assemble into enlarged pores that extrude the inner mitochondrial membrane into the cytosol where it ruptures and triggers pro-inflammatory cGAS/STING signalling |
10.1038/s41467-021-27851-y | 132,740,814 | Abstract BCL-2 proteins regulate mitochondrial poration in apoptosis initiation. How the pore-forming BCL-2 Effector BAK is activated remains incompletely understood mechanistically. Here we investigate autoactivation and direct activation by BH3-only proteins, which cooperate to lower BAK threshold in membrane poratio... | 10.1038/s41580-022-00564-w | This study elucidated how BAK becomes activated by BH3-only proteins, and how such activated BAK entities can trigger the activation of other dormant BAK proteins in trans involving asymmetric BH3-in-groove assemblies |
10.15252/embj.2020106438 | 62,182,231 | Abstract Bax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. This might involve their embedding in the cytosolic leaflet of the lipid bilayer, thus generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, Bax proteins might comprise part of ... | 10.1038/s41580-022-00564-w | This paper presented the high-resolution structure of the BAX core dimer as a part of the proteolipid wall of the pore in MOMP |
10.1126/sciimmunol.abd2591 | 122,868,201 | Gasdermins are executioners of the inflammatory cell death pathway pyroptosis that has so far been studied exclusively in vertebrates. In this study, we identified gasdermin E (GSDME) homologs in several invertebrate species including corals. We report that coral GSDME was cleaved by caspase 3 at two sites, yielding tw... | 10.1038/s41580-022-00564-w | This study elegantly showed how gasdermin proteolytic activation and pore formation have been evolutionarily conserved in invertebrates and vertebrates |
10.1038/s41467-022-30232-8 | 127,390,980 | Abstract Gasdermins are main effectors of pyroptosis, an inflammatory form of cell death. Released by proteolysis, the N-terminal gasdermin domain assembles large oligomers to punch lytic pores into the cell membrane. While the endpoint of this reaction, the fully formed pore, has been well characterized, the assembly ... | 10.1038/s41580-022-00564-w | This study provided structural insights into the dynamics of GSDMA3 pore formation, including critical mechanistic views on pre-pore assemblies |
10.1038/s41467-020-16823-3 | 125,039,274 | Abstract The MLKL pseudokinase is the terminal effector in the necroptosis cell death pathway. Phosphorylation by its upstream regulator, RIPK3, triggers MLKL’s conversion from a dormant cytoplasmic protein into oligomers that translocate to, and permeabilize, the plasma membrane to kill cells. The precise mechanisms u... | 10.1038/s41580-022-00564-w | This study identified differences in necroptotic signalling between species and suggested the existence of divergent regulatory mechanisms among orthologous MLKL pseudoenzymes |
10.1038/s41467-021-27032-x | 127,868,527 | Abstract The ancestral origins of the lytic cell death mode, necroptosis, lie in host defense. However, the dysregulation of necroptosis in inflammatory diseases has led to widespread interest in targeting the pathway therapeutically. This mode of cell death is executed by the terminal effector, the MLKL pseudokinase, ... | 10.1038/s41580-022-00564-w | This paper reported the structure of the human RIPK3 kinase domain, both alone and in complex with the MLKL pseudokinase, and revealed how human RIPK3 structurally differs from its mouse counterpart by its ability to maintain MLKL in an inactive conformation prior to induction of necroptosis |
10.1038/s41467-020-16887-1 | 62,377,032 | Abstract Mixed lineage kinase domain-like (MLKL) is the terminal protein in the pro-inflammatory necroptotic cell death program. RIPK3-mediated phosphorylation is thought to initiate MLKL oligomerization, membrane translocation and membrane disruption, although the precise choreography of events is incompletely underst... | 10.1038/s41580-022-00564-w | MLKL trafficking and plasma membrane accumulation at intercellular junctions act as crucial necroptosis checkpoints |
10.1126/sciadv.abc3465 | 62,270,056 | Gasdermin D (GSDMD) is a pore-forming protein that promotes pyroptosis and release of proinflammatory cytokines. Recent studies revealed that apoptotic caspase-8 directly cleaves GSDMD to trigger pyroptosis. However, the molecular requirements for caspase-8–dependent GSDMD cleavage and the physiological impact of this ... | 10.1038/s41580-022-00564-w | This study revealed the differential effect of caspase-8-mediated cleavage of GSDMD at D88 in TNF-induced lethality and anti-Yersinia defence |
10.4049/jimmunol.1100015 | 101,148,151 | Abstract Sleep regulates immune functions. We asked whether sleep can influence immunological memory formation. Twenty-seven healthy men were vaccinated against hepatitis A three times, at weeks 0, 8, and 16 with conditions of sleep versus wakefulness in the following night. Sleep was recorded polysomnographically, and... | 10.1038/s41577-019-0190-z | This experimental study looks at the role of sleep in promoting antigen-specific T cell-mediated immunity to a vaccination and also provides novel evidence that slow wave sleep activity immediately after vaccination drives T H 1 cell-mediated immune responses that persist over the following year |
10.1126/science.aat1650 | 40,573,769 | Sleep remains a major mystery of biology. In particular, little is known about the mechanisms that account for the drive to sleep. In an unbiased screen of more than 12,000 Drosophila lines, we identified a single gene, nemuri , that induces sleep. The NEMURI protein is an antimicrobial peptide that can be secreted ect... | 10.1038/s41577-019-0190-z | This ground-breaking study identifies an antimicrobial peptide, nemuri, that is a bona fide sleep homeostasis factor that drives prolonged ‘sleep’, as defined by locomotor activity, and also promotes survival after infection |
10.1302/0301-620x.89b7.19097 | 102,917,803 | We treated 22 patients with a diagnosis of primary frozen shoulder resistant to conservative treatment by manipulation under anaesthetic and arthroscopic release of the rotator interval, at a mean time from onset of 15 months (3 to 36). Biopsies were taken from this site and histological and immunocytochemical analysis... | 10.1038/s41572-022-00386-2 | Important basic science study looking at the pathophysiology of frozen shoulder. |
10.1002/jor.1100150316 | 82,443,448 | Abstract The purpose of this study was to test the hypothesis that specific cytokines are involved in the initiation and evolution of the fibrotic process in adhesive capsulitis of the shoulder. After approval from the Institutional Review Board, biopsies of shoulder capsule and synovium were collected during shoulder ... | 10.1038/s41572-022-00386-2 | First description of dysregulated cytokines and inflammation in frozen shoulder. |
10.1177/0363546517741127 | 101,287,405 | Background: The pathophysiological mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Alarmins (also known as danger signals) are endogenous molecules that are released into the extracellular milieu after infection or tissue injury and th... | 10.1038/s41572-022-00386-2 | Article discussing alarmins and clinical correlation of inflammation and pain. |
10.1038/s41586-021-04042-9 | 128,061,609 | Abstract Accurate navigation to a desired goal requires consecutive estimates of spatial relationships between the current position and future destination throughout the journey. Although neurons in the hippocampal formation can represent the position of an animal as well as its nearby trajectories 1–7 , their role in ... | 10.1038/s41583-022-00589-2 | Recent neurophysiological study showing that OFC neurons potentially encode the value of specific states in the state-transition graph |
10.1073/pnas.78.11.6628 | 61,163,977 | Activated glucocorticoid receptor protein, purified to 40-60% homogeneity from rat liver extracts, binds selectively in vitro to a cloned fragment of murine mammary tumor virus (MTV) DNA. The DNA fragment tested contains about half of the sequences present in intact MTV DNA, and its rate of transcription, like that of ... | 10.1038/s41586-019-1517-4 | A hormone-sensitive DNA sequence-specific transcription factor can bind near its Pol II target promoter |
10.1126/science.3059495 | 104,102,511 | Sp1 is a sequence-specific DNA binding protein that activates RNA polymerase II transcription from promoters that contain properly positioned GC boxes. A series of deletion mutants of Sp1 were expressed in Escherichia coli and used to identify separate regions of the protein that are important for three different bioch... | 10.1038/s41586-019-1517-4 | A transcription factor contains separate DNA binding and transactivation regions |
10.15252/embj.201796958 | 61,507,780 | Abstract In eukaryotic cells, RNA polymerase I (Pol I) synthesizes precursor ribosomal RNA (pre‐rRNA) that is subsequently processed into mature rRNA. To initiate transcription, Pol I requires the assembly of a multi‐subunit pre‐initiation complex (PIC) at the ribosomal RNA promoter. In yeast, the minimal PIC includes ... | 10.1038/s41586-019-1517-4 | This paper presents the structure of a Pol I pre-initiation complex |
10.1126/science.288.5470.1418 | 123,235,821 | We show that transcription factor IIH ERCC3 subunit, the DNA helicase responsible for adenosine triphosphate (ATP)–dependent promoter melting during transcription initiation, does not interact with the promoter region that undergoes melting but instead interacts with DNA downstream of this region. We show further that ... | 10.1038/s41586-019-1517-4 | Crosslinking shows that TFIIH acts on downstream DNA to open the promoter |
10.1126/science.1239053 | 17,610,508 | Transcription is reported to be spatially compartmentalized in nuclear transcription factories with clusters of RNA polymerase II (Pol II). However, little is known about when these foci assemble or their relative stability. We developed a quantitative single-cell approach to characterize protein spatiotemporal organiz... | 10.1038/s41586-019-1517-4 | Live-cell imaging visualizes Pol II clusters and their dynamics in human nuclei |
10.1038/s41467-018-07870-y | 125,048,907 | Abstract Transcription of eukaryotic protein-coding genes requires passage of RNA polymerase II (Pol II) through nucleosomes, but it is unclear how this is achieved. Here we report the cryo-EM structure of transcribing Saccharomyces cerevisiae Pol II engaged with a downstream nucleosome core particle at an overall reso... | 10.1038/s41586-019-1517-4 | Cryo-electron microscopy provides the structure of a Pol II–nucleosome complex |
10.1126/science.aau9904 | 101,940,951 | Genomic DNA forms chromatin, in which the nucleosome is the repeating unit. The mechanism by which RNA polymerase II (RNAPII) transcribes the nucleosomal DNA remains unclear. Here we report the cryo–electron microscopy structures of RNAPII-nucleosome complexes in which RNAPII pauses at the superhelical locations SHL(−6... | 10.1038/s41586-019-1517-4 | Cryo-electron microscopy provides the structures of several Pol II–nucleosome complexes |
10.1126/science.aam9288 | 104,392,378 | The internet—a vast network that enables simultaneous long-range classical communication—has had a revolutionary impact on our world. The vision of a quantum internet is to fundamentally enhance internet technology by enabling quantum communication between any two points on Earth. Such a quantum internet may operate in... | 10.1038/s41467-019-13332-w | A detailed overview and outlook on realising a quantum internet and quantum communications |
10.1038/s41598-019-55013-0 | 58,681,056 | Abstract Little attention was given to the interaction between tumor and stromal cells in urothelial bladder carcinoma (UBC). While recent studies point towards the existence of different fibroblast subsets, no comprehensive analyses linking different fibroblast markers to UBC patient survival have been performed so fa... | 10.1038/s41568-020-00313-1 | Analysing a cohort of 344 patients with bladder cancer, this study uses five fibroblast markers to highlight the need for multiple marker analysis when one is generating a prognosis using fibroblasts |
10.1038/s41467-018-05992-x | 124,219,643 | Abstract Cancers infiltrated with T-cells are associated with a higher likelihood of response to PD-1/PD-L1 blockade. Counterintuitively, a correlation between epithelial–mesenchymal transition (EMT)-related gene expression and T-cell infiltration has been observed across tumor types. Here we demonstrate, using The Can... | 10.1038/s41568-020-00313-1 | This study finds that non-haematopoietic stromal cells are a major source of EMT-related gene expression and that higher EMT-related and stromal gene expression is associated with poorer response to nivolumab and shorter progression-free and overall survival |
10.1158/0008-5472.can-19-2254 | 116,782,967 | Abstract Tumor-associated macrophages (TAM) play an indispensable role in the modulation of the cancer immune microenvironment. Despite the fact that TAMs may exert both antitumor and protumor activities, the molecular mechanisms involved remain poorly understood. Here, we characterized a subpopulation of TAMs expressi... | 10.1038/s41568-020-00313-1 | This study identifies of TAMs expressing a dendritic cell-specific C-type lectin which is shown to promote an anti-inflammatory environment. Neutralization of the lectin with an antibody augments pembrolizumab antitumour activity |
10.1126/sciadv.aav2437 | 100,385,607 | While a fraction of cancer patients treated with anti–PD-1 show durable therapeutic responses, most remain unresponsive, highlighting the need to better understand and improve these therapies. Using an in vivo screening approach with a customized shRNA pooled library, we identified DDR2 as a leading target for the enha... | 10.1038/s41568-020-00313-1 | This study uses functional genomics to find rational and effective therapeutic combinations of small molecules with checkpoint inhibitors in bladder and other cancer types. |
10.1038/s41598-018-29054-w | 79,709,605 | Abstract Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls.... | 10.1038/s41568-020-00313-1 | This study compares patients with bladder cancer and 11 healthy individuals and identifies unique urinary microbiota signatures as a potential means of prognosis and surveillance |
10.1126/science.aan3706 | 104,442,622 | Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced ... | 10.1038/s41568-020-00313-1 | This study highlights the negative impact antibiotics may have on immune checkpoint blockade and illuminates the potential that faecal microbiota transplantation may have in promoting patient response to immunotherapy |
10.1126/science.1198056 | 125,161,363 | Genomic analysis of a childhood cancer reveals markedly fewer mutations than what is typically seen in adult cancers. | 10.1038/s41572-019-0063-6 | This study is the first exome-level sequencing study of MB, identifying novel recurrent mutations targeting chromatin-modifying genes |
10.1093/med/9780190655341.003.0025 | 14,249,540 | This study summarizes a landmark study on the role of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) in patients with muscle-invasive bladder cancer. This randomized study of M-VAC plus cystectomy versus cystectomy alone suggested improved overall survival in patients receiv... | 10.1038/s41585-021-00505-w | This was the first randomized trial in MIBC that included pCR as a key end point, reported pCR results in neoadjuvant chemotherapy and control arms, and also survival results according to pCR status |
10.1159/000500620 | 32,307,179 | Many analyses of the efficacy of neoadjuvant treatment (NAT) for early breast cancer including a meta-analysis derived from 10 randomized trials came to the conclusion that patients who would achieve pathologic complete response (pCR) following NAT would experience significant improvement in disease-free and overall su... | 10.1038/s41585-021-00505-w | This guidance is intended to assist investigators in designing trials with the use of pCR as an early end point to support accelerated approval, and discusses accepted definitions of pCR in breast cancer, describes trial designs and patient populations in which pCR may be accepted as reasonably likely to predict clinic... |
10.1073/pnas.231473398 | 60,125,136 | The trithorax genes encode an evolutionarily conserved family of proteins that function to maintain specific patterns of gene expression throughout cellular development. Members of this protein family contain a highly conserved 130- to 140-amino acid motif termed the SET domain. We report the purification and molecular... | 10.1038/s41576-020-0278-0 | Together with Krogan et al. (2002), this critical study describes how COMPASS complexes were first identified biochemically in yeast |
10.1126/sciadv.1500447 | 20,452,875 | Over the past 4 years, nearly 100 exome sequencing studies have revealed the high frequency of mutations in the genes encoding the subunits of ATP-dependent chromatin remodelers in human cancer. Most of these mutations are within the genes encoding subunits of the BAF (Brg/Brahma-associated factors) or mSWI/SNF complex... | 10.1038/s41576-020-0278-0 | This article is an excellent review of SWI/SNF and its roles in malignancies |
10.1128/mcb.06092-11 | 103,312,101 | ABSTRACT Methylation of histone H3 lysine 4 (H3K4) in Saccharomyces cerevisiae is implemented by Set1/COMPASS, which was originally purified based on the similarity of yeast Set1 to human MLL1 and Drosophila melanogaster Trithorax (Trx). While humans have six COMPASS family members, Drosophila possesses a representativ... | 10.1038/s41576-020-0278-0 | This paper describes dSet1, the fly paralog of yeast Set1/COMPASS |
10.1101/gad.201327.112 | 61,719,234 | Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex... | 10.1038/s41576-020-0278-0 | This study identifies D. melanogaster Trr as the key enhancer monomethylase in flies |
10.1128/mcb.01181-13 | 81,557,876 | ABSTRACT Histone H3 lysine 4 (H3K4) can be mono-, di-, and trimethylated by members of the COMPASS ( com plex of p roteins as sociated with S et1) family from Saccharomyces cerevisiae to humans, and these modifications can be found at distinct regions of the genome. Monomethylation of histone H3K4 (H3K4me1) is relative... | 10.1038/s41576-020-0278-0 | This study shows that MLL3/4-COMPASS complexes function as major histone H3K4 monomethylases at enhancers in mammals |
10.1073/pnas.0812889106 | 39,985,693 | Mammalian SWI/SNF [also called BAF (Brg/Brahma-associated factors)] ATP-dependent chromatin remodeling complexes are essential for formation of the totipotent and pluripotent cells of the early embryo. In addition, subunits of this complex have been recovered in screens for genes required for nuclear reprogramming in X... | 10.1038/s41576-020-0278-0 | This study characterizes the embryonic stem cell-specific esBAF complex and its role in embryogenesis |
10.1242/dev.128892 | 104,130,074 | Precise gene expression ensures proper stem and progenitor cell differentiation, lineage commitment and organogenesis during mammalian development. ATP-dependent chromatin-remodeling complexes utilize the energy from ATP hydrolysis to reorganize chromatin and, hence, regulate gene expression. These complexes contain di... | 10.1038/s41576-020-0278-0 | This paper is a well-written review on the developmental functions of SWI/SNF complexes, as well as ISWI (imitation SWI) and CHD (chromodomain-helicase DNA-binding) proteins |
10.1073/pnas.250492697 | 104,311,998 | Malignant rhabdoid tumor (MRT) is an aggressive, highly lethal cancer of young children. Tumors occur in various locations, including kidney, brain, and soft tissues. Despite intensive therapy, 80% of affected children die, often within 1 year of diagnosis. The majority of MRT samples and cell lines have sustained bial... | 10.1038/s41576-020-0278-0 | This important paper highlights the function of SWI/SNF in MRT pathogenesis |
10.1126/science.aaz1776 | 125,172,438 | The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 8... | 10.1038/s41588-022-01249-y | A seminal paper by the GTEx consortium that characterizes the genetic regulation of gene expression and splicing phenotypes across dozens of tissue sources. |
10.1038/s41467-019-12228-z | 103,671,589 | Abstract Identifying methylation quantitative trait loci (meQTLs) and integrating them with disease-associated variants from genome-wide association studies (GWAS) may illuminate functional mechanisms underlying genetic variant-disease associations. Here, we perform GWAS of >415 thousand CpG methylation sites in who... | 10.1038/s41588-022-01249-y | A relevant paper that identifies mQTL effects in trans, and performs multiomic analysis to provide molecular characterization to genotype–phenotype associations. |
10.1002/mds.27431 | 20,683,820 | ABSTRACT Background : In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease (PD). Although recent validation studies suggest high accuracy, one unmet need is for highly specific criteria for clinical trials in early/de novo PD. Objectives : The... | 10.1038/s41583-021-00542-9 | This study describes high-specificity criteria for de novo PD according to the International Parkinson and Movement Disorder Society |
10.1002/mds.26605 | 104,224,529 | ABSTRACT Nonmotor manifestations of Parkinson's disease (PD) can begin well before motor PD begins. It is now clear, from clinical and autopsy studies, that there is significant Lewy‐type α‐synucleinopathy present outside the nigro‐striatal pathway and that this may underlie these nonmotor manifestations. This review d... | 10.1038/s41583-021-00542-9 | This review discusses neuropathological findings that may underlie nonmotor symptoms that either predate motor findings or occur as PD progresses |
10.1093/brain/awaa238 | 104,421,738 | Abstract Parkinson’s disease is characterized by the presence of abnormal, intraneuronal α-synuclein aggregates, which may propagate from cell-to-cell in a prion-like manner. However, it remains uncertain where the initial α-synuclein aggregates originate. We have hypothesized that Parkinson’s disease comprises two sub... | 10.1038/s41583-021-00542-9 | This paper discusses the existence of two subtypes of PD: brain-first, where α-syn pathology initially arises in the brain with secondary spreading to the peripheral autonomic nervous system, and body-first, where the pathology originates in the peripheral autonomic nervous system and then spreads to the brain |
10.1093/brain/awaa096 | 104,224,924 | Abstract In Parkinson’s disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the CNS. Here, we compare, in baboon monkeys, the pathological consequences of either intrastriatal or enteric injection of α-synuclein-containing Lewy body extracts from patients with Par... | 10.1038/s41583-021-00542-9 | This study showed that progression of α-syn pathology in a non-human primate model of PD might be either bottom-up or top-down in the absence of pathology through the vagus nerve and the dorsal motor nucleus of the vagus |
10.1126/sciimmunol.aag1266 | 38,335,369 | Radiotherapy and immunotherapy cooperate to generate antitumor immune responses for therapeutic gain. | 10.1038/s41573-018-0011-2 | This is a review of augmentation of radiotherapeutic effects by type I interferons |
10.1158/0008-5472.can-15-2125 | 104,249,651 | Abstract The most exciting recent advance for achieving durable management of advanced human cancers is immunotherapy, especially the concept of immune checkpoint blockade. However, with the exception of melanoma, most patients do not respond to immunotherapy alone. A growing body of work has shown that epigenetic drug... | 10.1038/s41573-018-0011-2 | This article discusses the potential of combining inhibition of genomic methylation and immunotherapy to augment effects of type I interferons |
10.1073/pnas.95.26.15623 | 125,283,596 | The pleiotropic activities of interferons (IFNs) are mediated primarily through the transcriptional regulation of many downstream effector genes. The mRNA profiles from IFN-α, -β, or -γ treatments of the human fibrosarcoma cell line, HT1080, were determined by using oligonucleotide arrays with probe sets corresponding ... | 10.1038/s41573-018-0011-2 | This is a seminal paper that defines the spectrum of ISGs |
10.1002/jlb.2mir0817-342r | 103,734,950 | Abstract Type I IFNs (α, β, and others) are a family of cytokines that are produced in physiological conditions as well as in response to the activation of pattern recognition receptors. They are critically important in controlling the host innate and adaptive immune response to viral and some bacterial infections, can... | 10.1038/s41573-018-0011-2 | This review discusses the balance in interferon responses resulting from negative molecular regulation |
10.1093/brain/awaa436 | 29,276,148 | Abstract Recent data suggest that multiple sclerosis white matter lesions surrounded by a rim of iron containing microglia, termed iron rim lesions, signify patients with more severe disease course and a propensity to develop progressive multiple sclerosis. So far, however, little is known regarding the dynamics of iro... | 10.1038/s41582-022-00624-x | This paper describes the evolution of MS lesions on the basis of iron content in microglia and macrophages |
10.1002/ana.25429 | 103,926,479 | Objective Central nervous system pathology in multiple sclerosis includes both focal inflammatory perivascular injury and injury to superficial structures, including the subpial region of the cortex, which reportedly exhibits a gradient of damage from the surface inward. We assessed how early in the multiple sclerosis ... | 10.1038/s41582-022-00624-x | This study demonstrates the surface-in distribution of pathology in the thalamus, which implicates CSF-derived injury |
10.1002/ana.25197 | 82,848,024 | Objective Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can these changes be identified in the patient early in the disease course? Methods To identify possible biomarkers linking meningeal inflammati... | 10.1038/s41582-022-00624-x | This study demonstrates the link between cortical damage in progressive MS and immune-derived products in the CSF and meninges |
10.1177/1352458519879303 | 123,826,793 | New DNA sequencing technologies have uncovered non-coding RNA (ncRNA) as a major player in regulating cellular processes and can no longer be dismissed as “junk” or “dark” RNA. Among the ncRNA, microRNA (miRNA) is arguably the most extensively characterized category and a number of studies have implicated them in regul... | 10.1038/s41582-022-00624-x | This study demonstrates the potential of microRNAs and exosomes as biomarkers in progressive MS |
10.1038/s41421-021-00243-8 | 104,412,588 | Abstract In mammals, many organs lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced cell reprogramming offers a temporally flexible and non-integrative strategy for altering cell fate... | 10.1038/s41582-022-00624-x | This study identifies a novel means to reprogramme functional properties of astrocytes |
10.1038/s41467-018-07785-8 | 102,025,928 | Abstract Epigenetic annotation studies of genetic risk variants for multiple sclerosis (MS) implicate dysfunctional lymphocytes in MS susceptibility; however, the role of central nervous system (CNS) cells remains unclear. We investigated the effect of the risk variant, rs7665090 G , located near NFKB1 , on astrocytes.... | 10.1038/s41582-022-00624-x | This study demonstrates the potential to manipulate astrocyte function on the basis of genetic profile |
10.1093/brain/awz287 | 83,326,994 | Radioligands targeting the 18 kDa translocator protein (TSPO) are increasingly used to visualise inflammation in the brain. Nutma et al. report that TSPO expression in multiple sclerosis lesions originates mainly from astrocytes and microglia, but is not restricted to cells with a specific pro-inflammatory phenotype. | 10.1038/s41582-022-00624-x | This study relates the expression of TSPO, which is used as a target in in vivo PET ligand studies, with cell type and activation state |
10.1093/jtm/taac077 | 142,957,968 | Description of the monkeypox 2022 outbreak is essentially based on historical cases mostly observed locally in Africa, but also from rare imported cases in four countries elsewhere, before the 2022 outbreak. This orthopoxvirus outbreak appears to be particularly well transmitted sexually possibly due to the high preval... | 10.1038/s41577-022-00775-4 | This paper describes the presence of genital lesions in recent cases involving young men engaging in activities with MSM |
10.3390/vaccines8030396 | 118,689,856 | The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to ex... | 10.1038/s41577-022-00775-4 | This study evaluates and characterizes the differences in protection provided by IMVAMUNE and ACAM2000 as post-exposure prophylactic vaccines in protection against MPXV infection |
10.1038/s41591-022-01907-y | 132,932,906 | Abstract The largest monkeypox virus (MPXV) outbreak described so far in non-endemic countries was identified in May 2022 (refs. 1–6 ). In this study, shotgun metagenomics allowed the rapid reconstruction and phylogenomic characterization of the first MPXV outbreak genome sequences, showing that this MPXV belongs to cl... | 10.1038/s41577-022-00775-4 | This recent article characterizes the MPXV outbreak genome sequence and highlights the involvement of host APOBEC3 protein in the virus evolution |
10.1126/science.1172377 | 61,917,890 | Card Sorting Monkeys Single-neuron studies in primates help to establish a detailed understanding of cognitive processing and to provide an experimental base for understanding the cognitive deficits incurred by patients who have suffered damage to areas of the brain. Buckley et al. (p. 52 ) present the results of an in... | 10.1038/s41583-020-0364-5 | This study examines the effects of selective lesions within different prefrontal regions on cognitive flexibility in shifting between abstract rules |
10.1093/cercor/bhz072 | 122,733,119 | Abstract Imaging and neural activity recording studies have shown activation in the primate prefrontal cortex when shifting attention between visual dimensions is necessary to achieve goals. A fundamental unanswered question is whether representations of these dimensions emerge from top-down attentional processes media... | 10.1038/s41583-020-0364-5 | This cross-species study reveals that both monkeys and humans show bias to a particular dimension in the WCST and that such biases are not dependent on the PFC |
10.1126/science.1072493 | 83,022,761 | Deriving the quantity of items is an abstract form of categorization. To explore it, monkeys were trained to judge whether successive visual displays contained the same quantity of items. Many neurons in the lateral prefrontal cortex were tuned for quantity irrespective of the exact physical appearance of the displays.... | 10.1038/s41583-020-0364-5 | This pioneering study shows how single neurons in the monkey PFC encode abstract numerical information |
10.1126/science.291.5502.312 | 83,338,729 | The ability to group stimuli into meaningful categories is a fundamental cognitive process. To explore its neural basis, we trained monkeys to categorize computer-generated stimuli as “cats” and “dogs.” A morphing system was used to systematically vary stimulus shape and precisely define the category boundary. Neural a... | 10.1038/s41583-020-0364-5 | This pioneering study shows how single neurons in the monkey PFC encode multifaceted categories |
10.1126/science.273.5281.1542 | 58,367,887 | Partitioning continuously varying stimuli into categories is a fundamental problem of perception. One solution to this problem, categorical perception, is known primarily from human speech, but also occurs in other modalities and in some mammals and birds. Categorical perception was tested in crickets by using two para... | 10.1038/s41583-020-0364-5 | This pioneering study provides solid evidence for category-guided behaviour in insects |
10.1126/science.1067653 | 86,498,107 | Functional brain organization of macaque monkeys and humans was directly compared by functional magnetic resonance imaging. Subjects of both species performed a modified Wisconsin Card Sorting Test that required behavioral flexibility in the form of cognitive set shifting. Equivalent visual stimuli and task sequence we... | 10.1038/s41583-020-0364-5 | This pioneering fMRI study in monkeys and humans reveals how shifting between rules is represented in the PFC |
10.1073/pnas.1206608109 | 103,713,218 | A considerable body of previous research on the prefrontal cortex (PFC) has helped characterize the regional specificity of various cognitive functions, such as cognitive control and decision making. Here we provide definitive findings on this topic, using a neuropsychological approach that takes advantage of a unique ... | 10.1038/s41583-020-0364-5 | This paper presents a comprehensive neuropsychological examination of the effects of brain lesions on cognitive flexibility in shifting between abstract rules |
10.1146/annurev.ne.19.030196.000545 | 20,864,194 | Cells in area TE of the inferotemporal cortex of the monkey brain selectively respond to various moderately complex object features, and those that cluster in a columnar region that runs perpendicular to the cortical surface respond to similar features. Although cells within a column respond to similar features, their ... | 10.1038/s41583-020-0364-5 | This comprehensive review describes the architecture of the ventral visual pathway of object recognition in primates |
10.1126/science.aam9690 | 38,432,768 | Neutrophils have been implicated as harmful cells in a variety of inappropriate inflammatory conditions where they injure the host, leading to the death of the neutrophils and their subsequent phagocytosis by monocytes and macrophages. Here we show that in a fully repairing sterile thermal hepatic injury, neutrophils a... | 10.1038/s41577-021-00571-6 | This work shows that neutrophils infiltrate sterile hepatic injury and support new vascular regrowth before re-entering the circulation and journeying via the lungs to the bone marrow, where they are cleared |
10.1136/jitc-2019-000473 | 82,585,850 | Background Understanding neutrophil heterogeneity and its relationship to disease progression has become a recent focus of cancer research. Indeed, several studies have identified neutrophil subpopulations associated with protumoral or antitumoral functions. However, this work has been hindered by a lack of widely acce... | 10.1038/s41577-021-00571-6 | This study defines neutrophil heterogeneity in human cancer using high-dimensional methods |
10.1126/science.aal5081 | 107,385,549 | A bona fide portrayal of tumor growth Bone has a well-established role in advanced cancer. It provides a supportive microenvironment for the growth of metastatic cells that escape the primary tumor, which ultimately leads to loss of bone mass. Engblom et al. show that bone may also contribute to early-stage tumorigenes... | 10.1038/s41577-021-00571-6 | This work shows that lung cancer-released circulating factors stimulate osteoblasts to mobilize Siglec-F high neutrophils, which home to the lungs and support cancer growth |
10.1126/science.1160631 | 38,304,971 | Some developmentally important genes can be regulated via two enhancers, one located nearby and the other, a "shadow" enhancer, 10 to 20 kilobases away. | 10.1038/s41576-020-00311-x | This article introduces the term ‘shadow enhancer’ to describe several enhancers important for dorsal–ventral patterning in the fly embryo and speculates on the evolutionary role of shadow enhancers |
10.7554/elife.59351 | 19,921,084 | Shadow enhancers, groups of seemingly redundant enhancers, are found in a wide range of organisms and are critical for robust developmental patterning. However, their mechanism of action is unknown. We hypothesized that shadow enhancers drive consistent expression levels by buffering upstream noise through a separation... | 10.1038/s41576-020-00311-x | This study in fly embryos shows that a pair of shadow enhancers, each regulated by different TFs, drives lower expression noise than do single or duplicated enhancers |
10.7554/elife.07956 | 122,748,756 | Metazoan genes are embedded in a rich milieu of regulatory information that often includes multiple enhancers possessing overlapping activities. In this study, we employ quantitative live imaging methods to assess the function of pairs of primary and shadow enhancers in the regulation of key patterning genes-knirps, hu... | 10.1038/s41576-020-00311-x | This article investigates how the activities of individual shadow enhancers interact to establish their combined activity in fly embryos and finds a wide range of possible interactions (superadditive, additive, subadditive and repressive) that may depend on the strength of the individual enhancers |
10.7554/elife.45325 | 121,619,456 | We previously showed in Drosophila melanogaster embryos that low-affinity Ultrabithorax (Ubx)-responsive shavenbaby (svb) enhancers drive expression using localized transcriptional environments and that active svb enhancers on different chromosomes tended to colocalize (Tsai et al., 2017). Here, we test the hypothesis ... | 10.1038/s41576-020-00311-x | This study describes how shadow enhancers may be critical for establishing or maintaining local regions of high TF concentrations required for achieving a certain threshold of gene expression |
10.1084/jem.20052036 | 84,574,187 | Unlike T-dependent immune responses against protein antigens, T-independent responses against polysaccharides confer long-lasting humoral immunity in the absence of recall responses and are not known to generate memory B cells. Here we report that polysaccharide antigens elicit memory B cells that are phenotypically di... | 10.1038/s41577-019-0244-2 | This study shows T cell-independent antigens can generate memory B cells that are phenotypically different from T cell-dependent memory B cells but that can last for months after immunization. |
10.1126/sciimmunol.aau6598 | 103,124,090 | Protective antibody responses to vaccination or infection depend on affinity maturation, a process by which high-affinity germinal center (GC) B cells are selected on the basis of their ability to bind, gather, and present antigen to T follicular helper (T fh ) cells. Here, we show that human GC B cells have intrinsica... | 10.1038/s41577-019-0244-2 | This study shows that human GC B cells make cytoskeletal rearrangements and form actin- and ezrin-rich pod-like extensions to test their affinity against membrane-bound antigens. |
10.1126/science.1201730 | 83,016,347 | A cell enrichment technique reveals the dynamics of the endogenous memory B cell response. | 10.1038/s41577-019-0244-2 | This study shows that owing to their high affinity and ability to be activated in the presence of neutralizing antibodies, isotype-switched IgG-expressing memory B cells prevail during the early phase of immune memory; however, once they disappear due to a shorter life span, IgM + memory B cells take on and lead the la... |
10.15252/embj.201592660 | 40,753,267 | Abstract The existence of a 30‐nm fiber as a basic folding unit for DNA packaging has remained a topic of active discussion. Here, we characterize the supramolecular structures formed by reversible Mg 2+ ‐dependent self‐association of linear 12‐mer nucleosomal arrays using microscopy and physicochemical approaches. The... | 10.1038/s41594-019-0368-x | This study shows that, with increasing cation concentrations, nucleosome arrays reversibly self-assemble into oligmeric structures in vitro instead of forming a 30-nm fiber |
10.1126/science.aag0025 | 38,361,847 | A close-up view inside the nucleus The nuclei of human cells contain 2 meters of genomic DNA. How does it all fit? Compaction starts with the DNA wrapping around histone octamers to form nucleosomes, but it is unclear how these further compress into mitotic chromosomes. Ou et al. describe a DNA-labeling method that all... | 10.1038/s41594-019-0368-x | Specific DNA staining in electron tomography allows visualization of chromatin ultrastructure in situ |
10.1523/jneurosci.04-08-02051.1984 | 62,231,961 | Previous studies have reported that some neurons in the inferior temporal (IT) cortex respond selectively to highly specific complex objects. In the present study, we conducted the first systematic survey of the responses of IT neurons to both simple stimuli, such as edges and bars, and highly complex stimuli, such as ... | 10.1038/s41583-020-00393-w | This is one of the earliest attempts to systematically analyse the selectivity of IT cells, including face cells, reporting a concentrated cluster of face cells in the fundus of the STS, likely corresponding to face patch MF |
10.1523/jneurosci.17-11-04302.1997 | 41,620,498 | Using functional magnetic resonance imaging (fMRI), we found an area in the fusiform gyrus in 12 of the 15 subjects tested that was significantly more active when the subjects viewed faces than when they viewed assorted common objects. This face activation was used to define a specific region of interest individually f... | 10.1038/s41583-020-00393-w | This landmark paper identified several regions in the human brain that respond selectively to faces, including one in the right fusiform gyrus and demonstrated this region is specialized for processing faces through a stringent set of tests |
10.1126/science.1119983 | 82,004,581 | Face perception is a skill crucial to primates. In both humans and macaque monkeys, functional magnetic resonance imaging (fMRI) reveals a system of cortical regions that show increased blood flow when the subject views images of faces, compared with images of objects. However, the stimulus selectivity of single neuron... | 10.1038/s41583-020-00393-w | This paper was the first to target an fMRI-identified region of the IT cortex for single-unit recording and found that face patches contain an extremely high concentration of face-selective cells, opening the possibility to systematically dissect the organization and coding properties of these cells |
10.1126/science.1194908 | 83,406,509 | Tuned for Faces The temporal lobe of macaques' brains contains six patches of face-selective cortex. This observation has prompted systems neuroscientists to ask, why so many and what do they do? Freiwald and Tsao (p. 845 ; see the Perspective by Connor ) targeted four of these regions for single-unit recordings and fo... | 10.1038/s41583-020-00393-w | This paper found that face patches form a functional hierarchy, with a view-specific representation in face patch ML, a mirror-symmetric representation in face patch AL and a view-invariant representation in face patch AM |
10.1126/science.1157436 | 123,615,703 | The brain processes objects through a series of regions along the ventral visual pathway, but the circuitry subserving the analysis of specific complex forms remains unknown. One complex form category, faces, selectively activates six patches of cortex in the macaque ventral pathway. To identify the connectivity of the... | 10.1038/s41583-020-00393-w | This paper combined electrical microstimulation with simultaneous fMRI and found that face patches are strongly and specifically connected to each other |
10.1073/pnas.1403112111 | 83,023,250 | Significance Humans and monkeys easily recognize objects in scenes. This ability is known to be supported by a network of hierarchically interconnected brain areas. However, understanding neurons in higher levels of this hierarchy has long remained a major challenge in visual systems neuroscience. We use computational ... | 10.1038/s41583-020-00393-w | This paper showed that units in a deep neural network trained to classify objects are predictive of neural responses in IT cortex and formalized the hypothesis that neural representations are equivalent if they are related by a linear transform |
10.1523/jneurosci.2609-12.2012 | 41,064,146 | Face-selective neural responses in the human fusiform gyrus have been widely examined. However, their causal role in human face perception is largely unknown. Here, we used a multimodal approach of electrocorticography (ECoG), high-resolution functional magnetic resonance imaging (fMRI), and electrical brain stimulatio... | 10.1038/s41583-020-00393-w | This study reported that, when the fusiform face area was stimulated, a human patient reported perceived distortions in the faces of people in the room |
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