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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10.1073/pnas.1605869113 | 83,176,715 | Infections due to clonal expansion of highly virulent bacterial strains are clear and present threats to human and animal health. Association of genetic changes with disease is now a routine, but identification of causative mutations that enable disease remains difficult. Campylobacter jejuni is an important zoonotic p... | 10.1038/s41579-018-0037-9 | This study reveals the very limited and specific genetic differences between an ovine C. jejuni abortifacient strain and a human C. jejuni diarrhoeal isolate |
10.1046/j.1365-2958.2000.01717.x | 123,562,627 | Campylobacter jejuni , a Gram‐negative spiral bacterium, is the most common bacterial cause of acute human gastroenteritis and is increasingly recognized for its association with the serious post‐infection neurological complications of the Miller–Fisher and Guillain–Barré syndromes. C. jejuni lipopolysaccharide (LPS) i... | 10.1038/s41579-018-0037-9 | This work demonstrates that the CPS determines the Penner serotype, which was previously thought to be due to LOS antigens |
10.1111/j.1365-2958.2004.04374.x | 82,463,381 | Summary We recently demonstrated that Campylobacter jejuni produces a capsular polysaccharide (CPS) that is the major antigenic component of the classical Penner serotyping system distinguishing Campylobacter into >60 groups. Although the wide variety of C. jejuni serotypes are suggestive of structural differences i... | 10.1038/s41579-018-0037-9 | This report provides a summary of different mechanisms that contribute to CPS diversity in C. jejuni |
10.1046/j.1365-2958.1999.01415.x | 29,308,611 | A genetic locus from Campylobacter jejuni 81‐176 (O:23, 36) has been characterized that appears to be involved in glycosylation of multiple proteins, including flagellin. The lipopolysaccharide (LPS) core of Escherichia coli DH5α containing some of these genes is modified such that it becomes immunoreactive with O:23 a... | 10.1038/s41579-018-0037-9 | This study presents the initial evidence that C. jejuni has a general protein glycosylation system |
10.1111/j.1365-2958.2004.03988.x | 20,713,076 | Summary Campylobacter jejuni is the leading cause of bacterial gastroenteritis in humans in developed countries throughout the world. This bacterium frequently promotes a commensal lifestyle in the gastrointestinal tracts of many animals including birds and consumption or handling of poultry meats is a prevalent source... | 10.1038/s41579-018-0037-9 | This is the first study to use transposon mutagenesis to identify C. jejuni genes required for commensalism in chickens |
10.1073/pnas.1703331114 | 62,029,334 | Campylobacter jejuni , a leading cause of bacterial gastroenteritis, is naturally competent. Like many competent organisms, C. jejuni restricts the DNA that can be used for transformation to minimize undesirable changes in the chromosome. Although C. jejuni can be transformed by C. jejuni -derived DNA, it is poorly tra... | 10.1038/s41579-018-0037-9 | This study shows that a methylase and specific modifications of a DNA sequence are important for DNA recognition by C. jejuni for natural transformation |
10.1073/pnas.1518952113 | 41,695,275 | Although it is known that diverse bacterial flagellar motors produce different torques, the mechanism underlying torque variation is unknown. To understand this difference better, we combined genetic analyses with electron cryo-tomography subtomogram averaging to determine in situ structures of flagellar motors that pr... | 10.1038/s41579-018-0037-9 | This work identifies a structural scaffold for incorporation of stator complexes into the C. jejuni flagellar motor that likely contributes to increased torque relative to other motile bacteria to power flagellar rotation and motility |
10.1111/j.1365-2958.2009.06797.x | 38,245,317 | Summary The food‐borne pathogen Campylobacter jejuni is dependent on a functional flagellum for motility and the export of virulence proteins that promote maximal host cell invasion. Both the flagellar and non‐flagellar proteins exported via the flagellar type III secretion system contain a sequence within the amino‐te... | 10.1038/s41579-018-0037-9 | This work identifies many potential proteins that are secreted by the flagella of C. jejuni that may have a role in host interactions |
10.1073/pnas.90.14.6884 | 18,551,543 | Bacterial invasion of six different human epithelial cell lines showed that some strains of the intestinal pathogen Campylobacter jejuni invaded intestinal cell lines at a level 10(2)-10(4) times higher than reported previously for other Campylobacter strains. Separately, urinary tract isolates of Citrobacter freundii ... | 10.1038/s41579-018-0037-9 | This is one of the first analyses of how C. jejuni invades human intestinal epithelial cells |
10.5194/ems2022-648 | 142,797,497 | <div> <p><span>The effects of floods are increasing as a result of global warming. Coastal, marine and watershed flooding, cause damage to people, the environment and economic activity. The damage to the economy is primarily affected by urban areas close to the coast and inland... | 10.1038/s41558-018-0340-5 | This study finds that up to 30% of the world’s total stock of manageable assets may be at risk due to climate change impacts, highlighting the potential costs of climate change as a major blind spot for companies and their investors |
10.1111/ppe.12416 | 60,718,746 | Abstract Background Evidence for risks of adverse maternal and birth outcomes in women with hyperemesis gravidarum ( HG ) is predominantly from small studies, unknown, or conflicting. Methods A population‐based cohort study using secondary health care records (Hospital Episode Statistics covering all of England from 19... | 10.1038/s41572-019-0110-3 | A recent and large population-based study elucidating HG complications for mother and baby. |
10.1038/s41467-018-03258-0 | 18,677,792 | Abstract Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3–2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for c... | 10.1038/s41572-019-0110-3 | The first GWAS of NVP and HG provided novel insight into the aetiology by revealing the placenta and appetite hormone gene GDF15 are the greatest risk factors for both NVP and HG. |
10.12688/wellcomeopenres.14818.1 | 85,525,238 | Background: Although nausea and vomiting are very common in pregnancy, their pathogenesis is poorly understood. We tested the hypothesis that circulating growth and differentiation factor 15 (GDF15) concentrations in early pregnancy, whose gene is implicated in hyperemesis gravidarum, are associated with nausea and vom... | 10.1038/s41572-019-0110-3 | The first study to show an association between serum levels of GDF15 and vomiting during the second trimester and between GDF15 and maternal antiemetic use, supporting the genetic findings and providing evidence for a novel therapeutic target for treating NVP and HG. |
10.1126/science.1253462 | 83,299,828 | Spatial and temporal dissection of the genomic changes occurring during the evolution of human non–small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations a... | 10.1038/s41568-018-0084-6 | This study nicely describes the genome evolution of lung cancer as determined by deep sequencing and demonstrates that subclonal diversification is driven by heterogeneous genetic instability |
10.1073/pnas.93.14.7081 | 40,689,576 | Increased 4N (G2/tetraploid) cell populations have been postulated to be genetically unstable intermediates in the progression to many cancers, but the mechanism by which they develop and their relationship to instability have been difficult to investigate in humans in vivo. Barrett's esophagus is an excellent model sy... | 10.1038/s41568-018-0084-6 | This is a landmark study into Barrett oesophagus that provides compelling evidence for tetraploidy as an early event in tumorigenesis |
10.1126/science.1104905 | 83,539,848 | Most tumor cells are characterized by increased genomic instability and chromosome segregational defects, often associated with hyperamplification of the centrosome and the formation of multipolar spindles. However, extra centrosomes do not always lead to multipolarity. Here, we describe a process of centrosomal cluste... | 10.1038/s41568-018-0084-6 | This paper provides a suitable explanation for the fact that tumour cells can tolerate centrosome amplifications |
10.1126/science.1210214 | 29,084,965 | Altering whole-chromosome number can directly increase chromosome structural damage in cancer cells. | 10.1038/s41568-018-0084-6 | This paper describes how missegregating chromosomes can break during cytokinesis, giving rise to non-reciprocal or unbalanced translocations |
10.1083/jcb.153.1.237 | 101,173,535 | When centrosomes are destroyed during prophase by laser microsurgery, vertebrate somatic cells form bipolar acentrosomal mitotic spindles (Khodjakov, A., R.W. Cole, B.R. Oakley, and C.L. Rieder. 2000. Curr. Biol. 10:59–67), but the fate of these cells is unknown. Here, we show that, although these cells lack the radial... | 10.1038/s41568-018-0084-6 | This paper nicely describes how centrosome defects affect the fidelity of cytokinesis and provides the first evidence that a human cell that is generated without a centrosome arrests in G1 |
10.1126/science.aaf8399 | 62,629,338 | Chromosomal chaos and tumor immunity Cancer immunotherapy produces durable clinical responses in only a subset of patients. Identification of tumor characteristics that correlate with responses could lead to predictive biomarkers and shed light on causal mechanisms. Davoli et al. found that human tumors with extensive ... | 10.1038/s41568-018-0084-6 | This study analyses 12 different human cancer types and demonstrates that highly aneuploid tumours display a reduction in infiltrating cytotoxic T cells, implying that aneuploidy does not stimulate an antitumour immune response |
10.1101/703140 | 117,655,969 | Abstract Genomic variation affects cellular networks by altering diverse molecular layers such as RNA levels, protein abundance, and post-translational protein modifications. However, it remains unclear how these different layers are affected by genetic polymorphisms and give rise to complex physiological phenotypes. T... | 10.1038/s41580-020-0231-2 | This recent study investigates quantitative trait loci on different molecular levels and how they mediate the effects of genomic variants in multilayered molecular networks |
10.1002/pmic.201800361 | 107,146,886 | Abstract A proteoform is a defined form of a protein derived from a given gene with a specific amino acid sequence and localized post‐translational modifications. In top‐down proteomic analyses, proteoforms are identified and quantified through mass spectrometric analysis of intact proteins. Recent technological develo... | 10.1038/s41580-020-0231-2 | This recent review discusses the current state of proteoform identification and quantification by top-down proteomics |
10.1146/annurev-anchem-071015-041535 | 62,494,733 | Proteins constitute a key class of molecular components that perform essential biochemical reactions in living cells. Whether the aim is to extensively characterize a given protein or to perform high-throughput qualitative and quantitative analysis of the proteome content of a sample, liquid chromatography coupled to t... | 10.1038/s41580-020-0231-2 | This in-depth review discusses current mass spectrometry techniques for bottom-up proteomics |
10.1038/s41467-020-15355-0 | 62,663,146 | Abstract Lithium-ion batteries have aided the portable electronics revolution for nearly three decades. They are now enabling vehicle electrification and beginning to enter the utility industry. The emergence and dominance of lithium-ion batteries are due to their higher energy density compared to other rechargeable ba... | 10.1038/s41467-023-35933-2 | We regard this paper as an excellent technical and historical account of positive electrode active materials. |
10.1101/gad.304113.117 | 61,061,486 | Maternal imprinting at the Xist gene is essential to achieve paternal allele-specific imprinted X-chromosome inactivation (XCI) in female mammals. However, the mechanism underlying Xist imprinting is unclear. Here we show that the Xist locus is coated with a broad H3K27me3 domain that is established during oocyte growt... | 10.1038/s41580-021-00438-7 | This article demonstrates that the transient maternal Xist imprint regulating iXCI in early mouse embryos is established through a large Polycomb domain upstream of Xist |
10.1073/pnas.1711206114 | 101,657,503 | X chromosome inactivation is an epigenetic dosage compensation mechanism in female mammals driven by the long noncoding RNA, Xist. Although recent genomic and proteomic approaches have provided a more global view of Xist’s function, how Xist RNA localizes to the inactive X chromosome (Xi) and spreads in cis remains unc... | 10.1038/s41580-021-00438-7 | Ridings-Figueroa et al. (2017) and Sunwoo et al. (2017) demonstrate the role of the protein CIZ1 in the coating of the Xi by Xist |
10.1126/science.aab2276 | 104,213,495 | The inactive X chromosome (Xi) serves as a model to understand gene silencing on a global scale. Here, we perform “identification of direct RNA interacting proteins” (iDRiP) to isolate a comprehensive protein interactome for Xist, an RNA required for Xi silencing. We discover multiple classes of interactors—including c... | 10.1038/s41580-021-00438-7 | Chu et al. (2015), McHugh et al. (2015) and Minajigi et al. (2015) provide a map of the proteins interacting with Xist RNA |
10.1126/science.aal2512 | 101,658,648 | Polycomb steps to inactivate X XX females silence one of their X chromosomes. This involves a process whereby a noncoding RNA known as Xist coats one of the X chromosomes and recruits chromatin silencing factors. The Polycomb complexes PRC1 and PRC2 are also known to be involved in X chromosome inactivation. Almeida et... | 10.1038/s41580-021-00438-7 | Pintacuda et al. (2017) and Almeida et al. (2017) demonstrate that a non-canonical PRC1 complex is directly recruited to the Xi by the Xist B-repeats, with PRC2 being recruited only subsequently |
10.1186/s13059-015-0728-8 | 103,779,034 | Abstract Background In mammals, one of the female X chromosomes and all imprinted genes are expressed exclusively from a single allele in somatic cells. To evaluate structural changes associated with allelic silencing, we have applied a recently developed Hi-C assay that uses DNase I for chromatin fragmentation to mous... | 10.1038/s41580-021-00438-7 | Rao et al. (2014) and Deng et al. (2015) reveal the bipartite organization of the Xi into two megadomains, in humans and mice |
10.1162/jocn.1997.9.5.648 | 41,749,140 | Nine previous positron emission tomography (PET) studies of human visual information processing were reanalyzed to determine the consistency across experiments of blood flow decreases during active tasks relative to passive viewing of the same stimulus array. Areas showing consistent decreases during active tasks inclu... | 10.1038/s41583-019-0212-7 | This study is an influential meta-analysis that revealed a network that is consistently suppressed during externally oriented tasks, which would later be called the default network |
10.1002/hbm.20113 | 83,552,263 | Abstract Recent neuroimaging studies have lead to the proposal that rest is characterized by an organized, baseline level of activity, a default mode of brain function that is suspended during specific goal‐oriented mental activity. Previous studies have shown that the primary function subserved by the default mode is ... | 10.1038/s41583-019-0212-7 | This article and Fox et al.’s (2005) paper provide evidence for an antagonistic relationship between the default network and networks involved in external attention |
10.1152/jn.00808.2018 | 20,641,899 | Examination of large-scale distributed networks within the individual reveals details of cortical network organization that are absent in group-averaged studies. One recent discovery is that a distributed transmodal network, often referred to as the “default network,” comprises two closely interdigitated networks, only... | 10.1038/s41583-019-0212-7 | This paper and Braga and Buckner (2017) demonstrate that the canonical default network comprises at least two distinct interwoven networks |
10.1073/pnas.1608282113 | 20,744,429 | Understanding how the structure of cognition arises from the topographical organization of the cortex is a primary goal in neuroscience. Previous work has described local functional gradients extending from perceptual and motor regions to cortical areas representing more abstract functions, but an overarching framework... | 10.1038/s41583-019-0212-7 | This paper draws attention to an orderly spatial relationship between the default network and other networks that repeat across the cortex |
10.1002/cne.24023 | 125,240,765 | The marmoset is an emerging animal model for large‐scale attempts to understand primate brain connectivity, but achieving this aim requires the development and validation of procedures for normalization and integration of results from many neuroanatomical experiments. Here we describe a computational pipeline for coreg... | 10.1038/s41583-019-0212-7 | This article is an open resource of aggregated anatomical tract tracing experiments that provides evidence for a default-network-like candidate in the marmoset monkey |
10.1073/pnas.1712431115 | 61,567,787 | The default mode network (DMN) is a collection of cortical brain regions that is active during states of rest or quiet wakefulness in humans and other mammalian species. A pertinent characteristic of the DMN is a suppression of local field potential gamma activity during cognitive task performance as well as during eng... | 10.1038/s41583-019-0212-7 | This rodent study demonstrates basal forebrain activity changes that are associated with behavioural state changes reminiscent of task suppression |
10.7554/elife.26196 | 4,860,206 | The adult primate visual system comprises a series of hierarchically organized areas. Each cortical area contains a topographic map of visual space, with different areas extracting different kinds of information from the retinal input. Here we asked to what extent the newborn visual system resembles the adult organizat... | 10.1038/s41583-019-0212-7 | This report suggests a mechanism by which specialized cortical areas are shaped through experience-dependent plasticity constrained by prenatal scaffolding |
10.1182/blood-2005-02-0494 | 20,233,246 | Abstract Heme oxygenase-1 (HO-1) is an intracellular enzyme that degrades heme and inhibits immune responses and inflammation in vivo. In most cell types, HO-1 is inducible by inflammatory stimuli and oxidative stress. Here we demonstrate that human monocyte-derived immature dendritic cells (iDCs) and several but not a... | 10.1038/s41577-020-00491-x | This important study is the first to describe the constitutive expression of HO-1 by immature DCs and its downregulation during DC maturation |
10.3390/cancers12020424 | 122,144,878 | Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>... | 10.1038/s41577-020-00491-x | This study shows a polymorphism resulting in increased HO-1 expression leads to increased survival in patients undergoing bone marrow transplantations |
10.18388/abp.2017_2542 | 104,128,695 | Inhibition of heme oxygenase-1 (HO-1, encoded by HMOX1), a cytoprotective, anti-apoptotic and anti-inflammatory enzyme, may be a valuable therapy in various pathophysiological processes, including tumorigenesis. We compared the effect of chemical inhibitors – metalloporphyrins, with genetic tools - shRNA and CRISPR/Cas... | 10.1038/s41577-020-00491-x | This article compares a number of methods to inhibit HO-1, with relevance to experimental modulation of HO-1 and development of therapeutic HO-1 inhibitors |
10.1038/s41591-022-01731-4 | 128,875,404 | Abstract High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as... | 10.1038/s41586-023-05707-3 | This study demonstrated that axi-cel is highly effective in the first-line therapy setting for high-risk LBCL |
10.1038/s41586-022-04489-4 | 136,428,887 | Abstract Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system 1 . We have previously shown that the disialoganglioside GD2 is highly expressed on H3K27M-mutated glioma cells and have demonstrated promising... | 10.1038/s41586-023-05707-3 | This study demonstrated clinical activity of GD2 CAR-T cells in diffuse midline gliomas |
10.1126/scisignal.abe2606 | 132,904,839 | Receptor pathway analysis informs structural modifications to CAR T cells that improve their function. | 10.1038/s41586-023-05707-3 | This study demonstrated diminished recruitment of proximal signaling molecules in CARs compared to TCRs |
10.1126/science.aba1786 | 83,541,606 | T cell exhaustion limits immune responses against cancer and is a major cause of resistance to chimeric antigen receptor (CAR)–T cell therapeutics. Using murine xenograft models and an in vitro model wherein tonic CAR signaling induces hallmark features of exhaustion, we tested the effect of transient cessation of rece... | 10.1038/s41586-023-05707-3 | This study showed that CAR-T functionality could be restored and features of exhaustion could be diminished by providing CAR-T cells with periods of rest |
10.1126/scitranslmed.abd8836 | 82,931,502 | The first clinically approved engineered chimeric antigen receptor (CAR) T cell therapies are remarkably effective in a subset of hematological malignancies with few therapeutic options. Although these clinical successes have been exciting, CAR T cells have hit roadblocks in solid tumors that include the lack of highly... | 10.1038/s41586-023-05707-3 | This study demonstrated that SynNotch-inducible CAR-T cells have lower tonic signalling, greater stemness and enhanced potency compared with conventional CAR-T cells |
10.1101/2022.06.17.496457 | 129,839,802 | Introductory paragraph While CAR T cells have altered the treatment landscape for B cell malignancies, the risk of on-target, off-tumor toxicity has hampered their development for solid tumors because most target antigens are shared with normal cells 1,2 . Researchers have attempted to apply Boolean logic gating to CAR... | 10.1038/s41586-023-05707-3 | LINK CAR utilizes proximal signalling molecules fused to membrane-bound scFvs to create an AND-gated CAR system. |
10.1038/s41586-021-04061-6 | 127,180,454 | Abstract The majority of oncogenic drivers are intracellular proteins, thus constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes 1 . However, most cancers have a modest mutational burden that is insufficient to generate response... | 10.1038/s41586-023-05707-3 | The authors developed a peptide-centric CAR targeting a peptide derived from an intracellular protein that is overexpressed in neuroblastoma |
10.1126/science.abm0594 | 133,296,737 | Making CAR T cells in vivo Cardiac fibrosis is the stiffening and scarring of heart tissue and can be fatal. Rurik et al . designed an immunotherapy strategy to generate transient chimeric antigen receptor (CAR) T cells that can recognize the fibrotic cells in the heart (see the Perspective by Gao and Chen). By injecti... | 10.1038/s41586-023-05707-3 | This study utilized CD5-targeting nanoparticles for in vivo gene engineering of T cells to treat cardiac fibrosis |
10.1101/gad.291518.116 | 107,164,384 | The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP... | 10.1038/s41467-019-08859-x | A comprehensive review that describes the current concepts of ARTD biology with a focus on new technologies to detect and study ADP-ribosylation. |
10.1126/science.1072221 | 20,855,366 | Poly(ADP-ribose) polymerase-1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network. PARP-1 is also a mediator of cell death after ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory processes. We show that PARP-1 activation is required for translocation of apopt... | 10.1038/s41467-019-08859-x | This is the first in a series of studies characterizing PAR as a cell death signal that induces release of AIF, elucidating the basis of the parthanatos cell death pathway. |
10.1038/srep18271 | 29,021,790 | Abstract ADP-ribosylation refers to the transfer of the ADP-ribose group from NAD + to target proteins post-translationally, either attached singly as mono(ADP-ribose) (MAR) or in polymeric chains as poly(ADP-ribose) (PAR). Though ADP-ribosylation is therapeutically important, investigation of this protein modification... | 10.1038/s41467-019-08859-x | This paper demonstrates the use of NUDIX enzymes to generate phosphoribose signatures for site-specific identification of ADP-ribosylation sites by MS. |
10.1111/febs.13811 | 105,346,859 | ADP ‐ribosylation is a conserved post‐translational protein modification that plays a role in all major cellular processes, particularly DNA repair, transcription, translation, stress response and cell death. Hence, dysregulation of ADP ‐ribosylation is linked to the physiopathology of several human diseases including ... | 10.1038/s41467-019-08859-x | This study describes the characterization of ENPP1 as the first mammalian enzyme without a NUDIX domain that generates phosphoribose remnants as a consequence of its phosphodiesterase activity against ADP-ribosylated proteins. |
10.1530/eje-18-0608 | 104,401,754 | Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Asses... | 10.1038/s41574-019-0221-7 | This publication reports the first focused clinical guidelines of ACC |
10.1210/jc.2018-01348 | 20,812,306 | Abstract Context Adrenocortical carcinoma (ACC) has a heterogeneous prognosis, and current medical therapies have limited efficacy in its advanced stages. Genome-wide multiomics studies identified molecular patterns associated with clinical outcome. Objective Here, we aimed at identifying a molecular signature useful f... | 10.1038/s41574-019-0221-7 | This paper presents the first comprehensive validation of ENS@T and TCGA studies |
10.1210/en.2015-1367 | 62,621,355 | Adrenocortical carcinoma (ACC) is a rare malignancy that harbors a dismal prognosis in advanced stages. Mitotane is approved as an orphan drug for treatment of ACC and counteracts tumor growth and steroid hormone production. Despite serious adverse effects, mitotane has been clinically used for decades. Elucidation of ... | 10.1038/s41574-019-0221-7 | This paper proposes SOAT1 as the molecular target of mitotane and remains to be validated |
10.1038/s44172-022-00012-9 | 142,892,503 | Abstract Space bioprocess engineering (SBE) is an emerging multi-disciplinary field to design, realize, and manage biologically-driven technologies specifically with the goal of supporting life on long term space missions. SBE considers synthetic biology and bioprocess engineering under the extreme constraints of the c... | 10.1038/s41467-023-37070-2 | A perspective paper highlighting the need to investigate space bioprocess engineering for future space missions, identifying key parameters to achieve this |
10.20944/preprints202207.0329.v1 | 142,494,703 | As renewed interest in human space-exploration intensifies, a coherent and modernized strategy for mission-design and planning has become increasingly crucial. Biotechnology has emerged as a promising approach to increase mission resilience, flexibility, and efficiency by virtue of its ability to efficiently utilize in... | 10.1038/s41467-023-37070-2 | A brilliant outline of strategic approaches to integrate biomanufacturing into space missions |
10.1098/rsif.2014.0715 | 104,248,532 | This paper demonstrates the significant utility of deploying non-traditional biological techniques to harness available volatiles and waste resources on manned missions to explore the Moon and Mars. Compared with anticipated non-biological approaches, it is determined that for 916 day Martian missions: 205 days of high... | 10.1038/s41467-023-37070-2 | This paper reviews highlights the potential for synthetic biology in human space exploration and ISRU |
10.32006/eeep.2021.1.2535 | 135,460,695 | The 3-days international virtual MELiSSA conference (November 3 to 5, 2020) about the closed life support systems was organized by the University of Ghent and IDDUP in collaboration with ESA/ESTEC (European Space Agency) and MELiSSA Foundation, and welcomed around 150 papers. The first day addressed the welcomed contri... | 10.1038/s41467-023-37070-2 | This review shows results and goals of the ESA MELiSSA project, which provides an excellent example of a project aiming to achieve loop-closure in space |
10.1126/science.218.4579.1273 | 3,728,673 | The polar ice sheets are rich sources of information on past atmospheric conditions, including paleoclimates. A new deep ice core has been drilled in south Greenland. Comparison of the oxygen isotopic profile with that from Camp Century and with a deep-sea foraminifera record indicates that the new core reaches back to... | 10.1038/s41558-020-0860-7 | First paper describing in depth the record of abrupt changes in Greenland ice cores |
10.1002/palo.20042 | 80,042,384 | Dansgaard‐Oeschger (D‐O) cycles are the most dramatic, frequent, and wide‐reaching abrupt climate changes in the geologic record. On Greenland, D‐O cycles are characterized by an abrupt warming of 10 ± 5°C from a cold stadial to a warm interstadial phase, followed by gradual cooling before a rapid return to stadial con... | 10.1038/s41558-020-0860-7 | Key reference for conceptual model and empirical evidence on the interplay between sea-ice cover, ocean stratification changes and abrupt warming |
10.1126/sciadv.aau6174 | 32,952,355 | The last glacial period was marked by pronounced millennial-scale variability in ocean circulation and global climate. Shifts in sea ice cover within the Nordic Seas are believed to have amplified the glacial climate variability in northern high latitudes and contributed to abrupt, high-amplitude temperature changes ov... | 10.1038/s41558-020-0860-7 | Documenting at high temporal resolution the phasing of first sea-ice diminution and a subsequent abrupt warming |
10.1175/jcli-d-17-0802.1 | 51,021,167 | The sensitivity of sea ice to the temperature of inflowing Atlantic water across the Greenland–Scotland Ridge is investigated using an eddy-resolving configuration of the Massachusetts Institute of Technology General Circulation Model with idealized topography. During the last glacial period, when climate on Greenland ... | 10.1038/s41558-020-0860-7 | Model experiments that indicate high sensitivity of ocean stratification and its potential to create abrupt sea-ice loss |
10.1029/2019gl083828 | 73,927,105 | Abstract Observed and model‐projected sea ice loss enhances warming in the Arctic. We investigate to what extent warming on Greenland can be attributed to changes in the sea ice cover in different parts of the Arctic. Using Climate Model Intercomparison Project phase 5 model projections of the future, we perform multil... | 10.1038/s41558-020-0860-7 | Shows that central Greenland temperatures at present are not particularly sensitive to regional Arctic sea-ice loss and associated warming. |
10.3390/cancers13246168 | 133,626,192 | By iCluster analysis, we found that the integrative molecular classification of the UM was primarily driven by DNA copy number variation on chromosomes 3, 6 and 8, differential methylation and expression of genes involved in the immune system, cell morphogenesis, movement and migration, and differential mutation of gen... | 10.1038/s41572-020-0158-0 | This report describes the use of different platforms to identify four subtypes of UM, each with different genetic, mRNA, long non-coding RNA and epigenetic patterns |
10.1158/0008-5472.can-04-1750 | 104,221,912 | Abstract Melanomas are notoriously difficult to classify because of a lack of discrete clinical and pathological stages. Here, we show that primary uveal melanomas surprisingly cluster into two distinct molecular classes based on gene expression profile. Genes that discriminate class 1 (low-grade) from class 2 (high-gr... | 10.1038/s41572-020-0158-0 | Expression of mRNA was used in this study to identify two different patterns, which had prognostic significance and led to the development of a clinical test for the prognostication of UM |
10.1126/science.1194472 | 20,791,849 | An Eye on Metastasis Despite the considerable progress being made in elucidating the cell biology of metastasis, little is known about the genetic alterations that promote metastasis of human tumors, the cause of most cancer deaths. A potentially important clue now emerges from the work of Harbour et al. (p. 1410 , pub... | 10.1038/s41572-020-0158-0 | Mutations in a gene on chromosome 3 BAP1 , were discovered in this work and shown to be associated with the development of metastases in UM |
10.4049/jimmunol.131.5.2587 | 139,042,681 | Abstract Intracameral inoculation of allogeneic P815 mastocytoma cells (DBA/2) into BALB/c mice resulted in progressively growing intraocular tumors. Intraocular tumor cells disseminated rapidly to the spleen and cervical lymph nodes, yet extraocular nests of tumor cells never developed into fulminant tumors. Further e... | 10.1038/s41572-020-0158-0 | The phenomenon of anterior chamber-associated immune deviation is described in this paper |
10.1097/iae.0000000000002440 | 59,204,025 | Purpose: To use multimodal imaging for identification of risk factors for choroidal nevus transformation into melanoma. Methods: Retrospective chart review of 3806 consecutive choroidal nevi with imaging and 2355 choroidal nevi with additional follow up to identify factors predictive of transformation of choroidal nevu... | 10.1038/s41572-020-0158-0 | This paper defines the characteristics of naevi that transform into UM |
10.1146/annurev-biodatasci-092820-114757 | 104,433,722 | The use of machine learning (ML) in healthcare raises numerous ethical concerns, especially as models can amplify existing health inequities. Here, we outline ethical considerations for equitable ML in the advancement of healthcare. Specifically, we frame ethics of ML in healthcare through the lens of social justice. W... | 10.1038/s41576-022-00465-w | This review identifies the many different ways that uncritical development of prediction models of health characteristics can entrench and exacerbate disparities for vulnerable populations |
10.1002/sim.7992 | 125,132,094 | When designing a study to develop a new prediction model with binary or time‐to‐event outcomes, researchers should ensure their sample size is adequate in terms of the number of participants ( n ) and outcome events ( E ) relative to the number of predictor parameters ( p ) considered for inclusion. We propose that the... | 10.1038/s41576-022-00465-w | This is an exploration of the key constraints that affect power and sample size in machine learning and prediction settings for binary and time-to-event outcomes |
10.1002/sim.7993 | 83,388,614 | In the medical literature, hundreds of prediction models are being developed to predict health outcomes in individuals. For continuous outcomes, typically a linear regression model is developed to predict an individual's outcome value conditional on values of multiple predictors (covariates). To improve model developme... | 10.1038/s41576-022-00465-w | This is an exploration of the key constraints that affect power and sample size in machine learning and prediction settings for continuous outcomes |
10.1093/nar/gkab397 | 45,409,536 | Abstract Long-read whole-genome sequencing analysis of DNA methylation would provide useful information on the chromosomal context of gene expression regulation. Here we describe the development of a method that improves the read length generated by using the bisulfite-sequencing-based approach. In this method, we comb... | 10.1038/s41576-022-00465-w | This study highlights the use of long-read sequencing of DNAm levels without bisulfite conversion |
10.1523/jneurosci.12-07-02549.1992 | 41,490,964 | We have found that the density of synapses in the stratum radiatum of the hippocampal CA1 region in the adult female rat is sensitive to estradiol manipulation and fluctuates naturally as the levels of ovarian steroids vary during the 5 d estrous cycle. In both cases, low levels of estradiol are correlated with lower s... | 10.1038/s41583-020-0362-7 | This foundational study links dynamic changes in hippocampal spine density to oestrous cyclicity, such that elevated spine density is correlated with higher levels of E 2 |
10.1523/jneurosci.5186-03.2004 | 62,622,184 | Estrogens have been described to induce synaptogenesis in principal neurons of the hippocampus and have been shown to be synthesized and released by exactly these neurons. Here, we have focused on the significance of local estrogen synthesis on spine synapse formation and the synthesis of synaptic proteins. To this end... | 10.1038/s41583-020-0362-7 | This study provides early evidence that locally synthesized oestrogens are critical for maintenance of hippocampal synapses |
10.1523/jneurosci.1968-08.2008 | 42,507,777 | The extracellular signal-regulated kinase (ERK) pathway is critical for various forms of learning and memory, and is activated by the potent estrogen 17β-estradiol (E 2 ). Here, we asked whether E 2 modulates memory via ERK activation and putative membrane-bound estrogen receptors (ERs). Using ovariectomized mice, we f... | 10.1038/s41583-020-0362-7 | This study reveals a crucial role for rapidly activated cell signalling activity in the memory-enhancing effects of E 2 |
10.1523/jneurosci.3011-17.2017 | 38,871,383 | Estradiol (E2) acutely potentiates glutamatergic synaptic transmission in the hippocampus of both male and female rats. Here, we investigated whether E2-induced synaptic potentiation occurs via presynaptic and/or postsynaptic mechanisms and which estrogen receptors (ERs) mediate E2's effects in each sex. Whole-cell vol... | 10.1038/s41583-020-0362-7 | This article provides a detailed example of how E 2 can work through sex-specific molecular mechanisms to produce the same functional outcomes in both males and females |
10.1073/pnas.1522150112 | 122,070,136 | Dramatic increases in hippocampal spine synapse density are known to occur within minutes of estrogen exposure. Until now, it has been assumed that enhanced spinogenesis increased excitatory input received by the CA1 pyramidal neurons, but how this facilitated learning and memory was unclear. Delivery of 17β-estradiol ... | 10.1038/s41583-020-0362-7 | This comprehensive study links rapid oestrogen-induced hippocampal spine formation with modulation of glutamatergic synapses and enhancement of spatial and recognition memory |
10.1210/en.2015-1959 | 2,652,007 | Abstract 17β-estradiol (E2) rapidly, within minutes, activates behaviors and cognition by binding to membrane estrogen receptors, activating cell signaling cascades and increasing dendritic spines. In female rodents, E2 enhances spatial memory within 2–4 hours, and spine density is increased in the CA1 area of the hipp... | 10.1038/s41583-020-0362-7 | This study shows that rapid E 2 signalling produces parallel effects on hippocampal structure and function in males comparable to historical findings in females |
10.1136/bmj.n826 | 61,931,151 | Abstract Objective To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust. Design Data resource comprising linked person level records from national healthcar... | 10.1038/s41591-022-02166-7 | This article presents an England-wide health data resource that enables whole population research on COVID-19. |
10.1111/bcp.14184 | 54,037,438 | Medicines are a major component of modern healthcare delivery, both in resource consumption and as drivers of innovation. The ever‐increasing application of digitalisation within day‐to‐day living and as part of our healthcare systems—with the resultant data generation—presents the opportunity to better define the popu... | 10.1038/s41591-022-02166-7 | This paper summarizes the development of the Scottish Prescribing Information System and reports on its use to promote the safe and effective use of medicines. |
10.1126/science.aaf2403 | 62,604,497 | Analysis of the pattern of proteins or messengerRNAs (mRNAs) in histological tissue sections is a cornerstone in biomedical research and diagnostics. This typically involves the visualization of a few proteins or expressed genes at a time. We have devised a strategy, which we call “spatial transcriptomics,” that allows... | 10.1038/s41586-021-03634-9 | This paper was the first to perform array-based spatial transcriptomics, using positional barcodes at a resolution of 200 μm, and demonstrated the approach on the mouse olfactory bulb |
10.1126/science.aaw1219 | 20,831,748 | Spatial positions of cells in tissues strongly influence function, yet a high-throughput, genome-wide readout of gene expression with cellular resolution is lacking. We developed Slide-seq, a method for transferring RNA from tissue sections onto a surface covered in DNA-barcoded beads with known positions, allowing the... | 10.1038/s41586-021-03634-9 | This paper describes Slide-seq, an array-based method with 10μm resolution, performed in the cerebellum and hippocampus |
10.1126/science.1250212 | 41,741,358 | Transcripts Visualized in Situ Despite advances, current methods for single-cell sequencing are unable to resolve transcript location within the cell, so Lee et al. (p. 1360 , published online 27 February) developed a method of fluorescent in situ RNA sequencing (FISSEQ) that works in vivo to show messenger RNA localiz... | 10.1038/s41586-021-03634-9 | This paper introduced an untargeted ISS method, FISSEQ, that generated 30 base reads from 8,102 genes in human primary fibroblasts |
10.30535/mto.15.3.16 | 114,437,311 | Sweet Anticipation is partially devoted to explaining why listeners have a positive response to music that they can successfully predict. The book also presents evidence that the pleasure felt when expectations are met is especially great when these expectations are unconscious. I give examples from popular and classic... | 10.1038/s41583-022-00578-5 | In this book, Huron draws on evolutionary theory and statistical learning to propose a general theory of musical expectation |
10.1017/s0140525x08005542 | 87,870,243 | Abstract There is certainly a need for a framework to guide the study of the physiological mechanisms underlying the experience of music and the emotions that music evokes. However, this framework should be organised hierarchically, with musical anticipation as its fundamental mechanism. | 10.1038/s41583-022-00578-5 | This is the foundation for the PCM model used in this Review |
10.1073/pnas.1730682100 | 38,597,482 | Musicians recognize pitch as having two dimensions. On the keyboard, these are illustrated by the octave and the cycle of notes within the octave. In perception, these dimensions are referred to as pitch height and pitch chroma, respectively. Pitch chroma provides a basis for presenting acoustic patterns (melodies) tha... | 10.1038/s41583-022-00578-5 | Using fMRI data, this study shows that pitch chroma is represented anterior to the primary auditory cortex, and pitch height is represented posterior to the primary auditory cortex |
10.1162/089892998563121 | 107,203,148 | In order to test the language-specificity of a known neural correlate of syntactic processing [the P600 event-related brain potential (ERP) component], this study directly compared ERPs elicited by syntactic incongruities in language and music. Using principles of phrase structure for language and principles of harmony... | 10.1038/s41583-022-00578-5 | This classic study compares responses to syntactic incongruities in both language and Western tonal music |
10.1162/jocn.2007.19.5.893 | 20,642,068 | When we listen to rhythm, we often move spontaneously to the beat. This movement may result from processing of the beat by motor areas. Previous studies have shown that several motor areas respond when attending to rhythms. Here we investigate whether specific motor regions respond to beat in rhythm. We predicted that ... | 10.1038/s41583-022-00578-5 | This fMRI study investigates participants listening to rhythms of varied complexity |
10.1073/pnas.191355898 | 82,948,425 | We used positron emission tomography to study neural mechanisms underlying intensely pleasant emotional responses to music. Cerebral blood flow changes were measured in response to subject-selected music that elicited the highly pleasurable experience of “shivers-down-the-spine” or “chills.” Subjective reports of chill... | 10.1038/s41583-022-00578-5 | This seminal positron emission tomography study shows that the experience of musical chills correlates with activity in the reward system |
10.1093/scan/nsaa056 | 37,921,028 | Abstract Interpersonal coordination is a core part of human interaction, and its underlying mechanisms have been extensively studied using social paradigms such as joint finger-tapping. Here, individual and dyadic differences have been found to yield a range of dyadic synchronization strategies, such as mutual adaptati... | 10.1038/s41583-022-00578-5 | This EEG study shows that differences in interpersonal synchronization are reflected by activity in a temporoparietal network |
10.1207/s15516709cog2601_1 | 123,087,448 | Abstract We address how listeners perceive temporal regularity in music performances, which are rich in temporal irregularities. A computational model is described in which a small system of internal self‐sustained oscillations, operating at different periods with specific phase and period relations, entrains to the rh... | 10.1038/s41583-022-00578-5 | This article proposes an oscillator-based approach for the perception of temporal regularity in music |
10.1098/rstb.2014.0169 | 107,318,471 | This paper considers neuronal architectures from a computational perspective and asks what aspects of neuroanatomy and neurophysiology can be disclosed by the nature of neuronal computations? In particular, we extend current formulations of the brain as an organ of inference—based upon hierarchical predictive coding—an... | 10.1038/s41583-020-0287-1 | This theoretical paper provides a neurobiological account of how the brain coordinates first-order (that is, perceptual content) and second-order (that is, modulatory gain control by the pulvinar) neural populations to optimize hierarchical predictive inference |
10.1126/science.aaa8694 | 104,080,929 | Looming in on the threat-response circuit What are the neural elements that transmit threat-relevant inputs in the brain? Shang et al. systematically identified the key neuronal subtypes in the mouse superior colliculus underlying active avoidance and defensive-like behaviors. They found a pathway that responded to loo... | 10.1038/s41583-020-0287-1 | This study demonstrates that a pathway from the SC to the parabigeminal nucleus that responds to looming visual stimuli also evokes fearful, defensive behaviour in mice |
10.1073/pnas.1701003114 | 102,446,371 | Models of visual attention postulate the existence of a bottom-up saliency map that is formed early in the visual processing stream. Although studies have reported evidence of a saliency map in various cortical brain areas, determining the contribution of phylogenetically older pathways is crucial to understanding its ... | 10.1038/s41583-020-0287-1 | This study demonstrates, using simultaneous recordings of the SC and V1 in Rhesus monkeys, that differential responses to saliency occurred in the SC before V1 |
10.1152/physrev.00006.2016 | 125,276,646 | Many cellular functions are regulated by calcium (Ca 2+ ) signals that are generated by different signaling pathways. One of these is the inositol 1,4,5-trisphosphate/calcium (InsP 3 /Ca 2+ ) signaling pathway that operates through either primary or modulatory mechanisms. In its primary role, it generates the Ca 2+ tha... | 10.1038/s41577-018-0110-7 | This paper provides an excellent and comprehensive review on Ins(1,4,5)P 3 signalling pathways in health and disease |
10.1146/annurev-biochem-060614-034216 | 62,147,798 | In the last 5 years, most of the molecules that control mitochondrial Ca 2+ homeostasis have been finally identified. Mitochondrial Ca 2+ uptake is mediated by the Mitochondrial Calcium Uniporter (MCU) complex, a macromolecular structure that guarantees Ca 2+ accumulation inside mitochondrial matrix upon increases in c... | 10.1038/s41577-018-0110-7 | This is an excellent review on mitochondrial Ca 2+ signalling and its role in shaping cell signalling and cell function |
10.1111/j.1600-065x.2009.00816.x | 83,333,038 | Summary: For more than 25 years, it has been widely appreciated that Ca 2+ influx is essential to trigger T‐lymphocyte activation. Patch clamp analysis, molecular identification, and functional studies using blockers and genetic manipulation have shown that a unique contingent of ion channels orchestrates the initiatio... | 10.1038/s41577-018-0110-7 | References 4 and 11 are detailed review articles that provide excellent overviews of different ions and ion channels and their role in controlling innate and adaptive immunity |
10.1073/pnas.0908099107 | 122,987,031 | Mitochondrial Ca 2+ efflux is linked to numerous cellular activities and pathophysiological processes. Although it is established that an Na + -dependent mechanism mediates mitochondrial Ca 2+ efflux, the molecular identity of this transporter has remained elusive. Here we show that the Na + /Ca 2+ exchanger NCLX is en... | 10.1038/s41577-018-0110-7 | This paper is the first to identify the molecular identity of the Na + /Ca 2+ exchanger in mitochondria (NCLX), which is responsible for Ca 2+ extrusion from mitochondria |
10.1152/physrev.00020.2014 | 104,389,224 | Store-operated calcium channels (SOCs) are a major pathway for calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca 2+ from the endo... | 10.1038/s41577-018-0110-7 | This is an exhaustive review that provides an outstanding overview of store-operated Ca 2+ channels, including their biophysical properties, activation, regulation and cellular function |
10.1152/physiol.00011.2017 | 39,832,546 | In this review article, we discuss the different gene products and translational variants of ORAI proteins and their contribution to the makeup of different native calcium-conducting channels with distinct compositions and modes of activation. We also review the different modes of regulation of these distinct calcium c... | 10.1038/s41577-018-0110-7 | This review provides a brief historical overview of store-operated Ca 2 + channels and a summary of the various native Ca 2 + channels encoded by ORAI proteins. |
10.1038/ncomms14714 | 19,348,642 | Abstract Store-operated Ca 2+ entry (SOCE) through Ca 2+ release-activated Ca 2+ (CRAC) channels is critical for lymphocyte function and immune responses. CRAC channels are hexamers of ORAI proteins that form the channel pore, but the contributions of individual ORAI homologues to CRAC channel function are not well und... | 10.1038/s41577-018-0110-7 | This paper provides the first evidence that ORAI2 channels act as negative modulators of SOCE and T cell immunity |
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