Abstract：
:Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P=8.6 × 10(-9) and P=6.4 × 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR=1.30; P=0.0024).
journal_name
Nat Communjournal_title
Nature communicationsauthors
Swaminathan B,Thorleifsson G,Jöud M,Ali M,Johnsson E,Ajore R,Sulem P,Halvarsson BM,Eyjolfsson G,Haraldsdottir V,Hultman C,Ingelsson E,Kristinsson SY,Kähler AK,Lenhoff S,Masson G,Mellqvist UH,Månsson R,Nelander S,Oladoi
10.1038/ncomms8213subject
Has Abstractpub_date
2015-05-26 00:00:00pages
7213issn
2041-1723pii
ncomms8213journal_volume
6pub_type
杂志文章,meta分析,多中心研究abstract：:Medulloblastoma (MB) is the most common malignant brain tumor in children and among the subtypes, Group 3 MB has the worst outcome. Here, we perform an in vivo, patient-specific screen leading to the identification of Otx2 and c-MYC as strong Group 3 MB inducers. We validated our findings in human cerebellar organoids...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-019-13989-3
更新日期：2020-01-29 00:00:00
abstract：:Human hnRNP A2/B1 is an RNA-binding protein that plays important roles in many biological processes, including maturation, transport, and metabolism of mRNA, and gene regulation of long noncoding RNAs. hnRNP A2/B1 was reported to control the microRNAs sorting to exosomes and promote primary microRNA processing as a po...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-017-02770-z
更新日期：2018-01-29 00:00:00
abstract：:This corrects the article DOI: 10.1038/ncomms14778. ...
journal_title：Nature communications
pub_type： 杂志文章,已发布勘误
doi：10.1038/ncomms15574
更新日期：2017-05-24 00:00:00
abstract：:Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation of AR signalling remains the main driver of castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased characterisation of LNCaP cells chronically exposed to multiple AR inhibitors (...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-16126-7
更新日期：2020-05-19 00:00:00
abstract：:Genetic mutations predispose the serine protease inhibitor α1-antitrypsin to misfolding and polymerisation within hepatocytes, causing liver disease and chronic obstructive pulmonary disease. This misfolding occurs via a transiently populated intermediate state, but our structural understanding of this process is limi...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-20147-7
更新日期：2020-12-11 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature communications
pub_type： 已发布勘误
doi：10.1038/s41467-019-11219-4
更新日期：2019-07-10 00:00:00
abstract：:One primary reason that makes single-cell RNA-seq analysis challenging is dropouts, where the data only captures a small fraction of the transcriptome of each cell. Almost all computational algorithms developed for single-cell RNA-seq adopted gene selection, dimension reduction or imputation to address the dropouts. H...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-14976-9
更新日期：2020-03-03 00:00:00
abstract：:The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enrich...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms6890
更新日期：2015-01-19 00:00:00
abstract：:Device performance and in particular device stability for blue perovskite light-emitting diodes (PeLEDs) remain considerable challenges for the whole community. In this manuscript, we conceive an approach by tuning the 'A-site' cation composition of perovskites to develop blue-emitters. We herein report a Rubidium-Ces...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-019-09794-7
更新日期：2019-04-23 00:00:00
abstract：:FBXW2 inhibits proliferation of lung cancer cells by targeting SKP2 for degradation. Whether and how FBXW2 regulates tumor invasion and metastasis is previously unknown. Here, we report that FBXW2 is an E3 ligase for β-catenin. FBXW2 binds to β-catenin upon EGF-AKT1-mediated phosphorylation on Ser552, and promotes its...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-019-09289-5
更新日期：2019-03-27 00:00:00
abstract：:Missense mutations in Valosin-Containing Protein (VCP) are linked to diverse degenerative diseases including IBMPFD, amyotrophic lateral sclerosis (ALS), muscular dystrophy and Parkinson's disease. Here, we characterize a VCP-binding co-factor (SVIP) that specifically recruits VCP to lysosomes. SVIP is essential for l...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-20796-8
更新日期：2021-01-21 00:00:00
abstract：:Determining whether recurrent but rare cancer mutations are bona fide driver mutations remains a bottleneck in cancer research. Here we present the most comprehensive analysis of murine leukemia virus-driven lymphomagenesis produced to date, sequencing 700,000 mutations from >500 malignancies collected at time points ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-05069-9
更新日期：2018-07-09 00:00:00
abstract：:The original version of this article contained an error in the spelling of the author Christian A.M. Wilson, which was incorrectly given as Christian M.A. Wilson. This has now been corrected in both the PDF and HTML versions of the article. ...
journal_title：Nature communications
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41467-017-02384-5
更新日期：2017-12-14 00:00:00
abstract：:Because the surface-to-volume ratio of quasi-two-dimensional materials is extremely high, understanding their surface characteristics is crucial for practically controlling their intrinsic properties and fabricating p-type and n-type layered semiconductors. Van der Waals crystals are expected to have an inert surface ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-03824-6
更新日期：2018-04-12 00:00:00
abstract：:The brain identifies potentially salient features within continuous information streams to process hierarchical temporal events. This requires the compression of information streams, for which effective computational principles are yet to be explored. Backpropagating action potentials can induce synaptic plasticity in...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-15367-w
更新日期：2020-03-25 00:00:00
abstract：:To learn, obtain reward and survive, humans and other animals must monitor, approach and act on objects that are associated with variable or unknown rewards. However, the neuronal mechanisms that mediate behaviours aimed at uncertain objects are poorly understood. Here we demonstrate that a set of neurons in an intern...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms12735
更新日期：2016-09-14 00:00:00
abstract：:Circadian clock mechanisms have been extensively investigated but the main rate-limiting step that determines circadian period remains unclear. Formation of a stable complex between clock proteins and CK1 is a conserved feature in eukaryotic circadian mechanisms. Here we show that the FRQ-CK1 interaction, but not FRQ ...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-019-12239-w
更新日期：2019-09-25 00:00:00
abstract：:Frequency tuning within the auditory papilla of most non-mammalian species is electrical, deriving from ion-channel resonance within their sensory hair cells. In contrast, tuning within the mammalian cochlea is mechanical, stemming from active mechanisms within outer hair cells that amplify the basilar membrane travel...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms13133
更新日期：2016-10-31 00:00:00
abstract：:Immune responses are crucial not only for host defence against pathogens but also for tissue maintenance and repair after injury. Lymphocytes are involved in the healing process after tissue injury, including bone fracture and muscle damage. However, the specific immune cell subsets and mediators of healing are not en...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms10928
更新日期：2016-03-11 00:00:00
abstract：:To function, biomolecules require sufficient specificity of interaction as well as stability to live in the cell while still being able to move. Thermodynamic stability of only a limited number of specific structures is important so as to prevent promiscuous interactions. The individual interactions in proteins, there...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-19560-9
更新日期：2020-11-23 00:00:00
abstract：:Hedgehog (Hh) signalling regulates embryonic development and adult tissue homoeostasis. Mutations of its pathway components including Suppressor of Fused (Sufu) and Gli/Ci predispose to cancers and congenital anomalies. The Sufu-Gli protein complex occupies a central position in the vertebrate Hh signalling pathway, e...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms3608
更新日期：2013-01-01 00:00:00
abstract：:Ribosomal RNA (rRNA) is most highly expressed in rapidly growing bacteria and is drastically downregulated under stress conditions by the global transcriptional regulator DksA and the alarmone ppGpp. Here, we determined cryo-electron microscopy structures of the Escherichia coli RNA polymerase (RNAP) σ70 holoenzyme du...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-20776-y
更新日期：2021-01-22 00:00:00
abstract：:Under hypoxia, most of glucose is converted to secretory lactate, which leads to the overuse of glutamine-carbon. However, under such a condition how glutamine nitrogen is disposed to avoid over-accumulating ammonia remains to be determined. Here we identify a metabolic flux of glutamine to secretory dihydroorotate, w...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-08033-9
更新日期：2019-01-14 00:00:00
abstract：:Biocatalytic cyclization is highly desirable for efficient synthesis of biologically derived chemical substances, such as the commodity chemicals ε-caprolactam and δ-valerolactam. To identify biocatalysts in lactam biosynthesis, we develop a caprolactam-detecting genetic enzyme screening system (CL-GESS). The Alcalige...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-07488-0
更新日期：2018-11-29 00:00:00
abstract：:A human cell contains hundreds to thousands of mitochondrial DNA (mtDNA) packaged into nucleoids. Currently, the segregation and allocation of nucleoids are thought to be passively determined by mitochondrial fusion and division. Here we provide evidence, using live-cell super-resolution imaging, that nucleoids can be...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-18202-4
更新日期：2020-09-08 00:00:00
abstract：:Reliable prediction of seasonal precipitation in the southwestern US (SWUS) remains a challenge with significant implications for the economy, water security and ecosystem management of the region. Winter precipitation in the SWUS has been linked to several climate modes, including the El Niño-Southern Oscillation (EN...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-04722-7
更新日期：2018-06-13 00:00:00
abstract：:The presence of a di-unsaturated highly branched isoprenoid (HBI) lipid biomarker (diene II) in Southern Ocean sediments has previously been proposed as a proxy measure of palaeo Antarctic sea ice. Here we show that a source of diene II is the sympagic diatom Berkeleya adeliensis Medlin. Furthermore, the propensity fo...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms12655
更新日期：2016-08-30 00:00:00
abstract：:Microbiome-derived metabolites influence intestinal homeostasis and regulate graft-versus-host disease (GVHD), but the molecular mechanisms remain unknown. Here we show the metabolite sensor G-protein-coupled receptor 43 (GPR43) is important for attenuation of gastrointestinal GVHD in multiple clinically relevant muri...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-06048-w
更新日期：2018-09-10 00:00:00
abstract：:Despite the fundamental importance of efficient and selective synthesis of widely useful alkylarenes, the direct catalytic C(sp2)-H alkylation of unactivated arenes with a readily available alkyl halide remains elusive. Here, we report the catalytic C(sp2)-H alkylation reactions of unactivated arenes with alkyl bromid...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-19038-8
更新日期：2020-10-19 00:00:00
abstract：:Pupylation is a posttranslational protein modification occurring in mycobacteria and other actinobacteria that is functionally analogous to ubiquitination. Here we report the crystal structures of the modification enzymes involved in this pathway, the prokaryotic ubiquitin-like protein (Pup) ligase PafA and the depupy...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms2009
更新日期：2012-01-01 00:00:00
