解剖学和形态学
麻醉学
听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
免疫学
传染病
综合和补充性医学
医学伦理学
医学信息学
医学实验室技术
医学,全科和内科
医学,法律
医学,研究和试验
神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
肿瘤学
眼科学
整形外科学
耳鼻喉科学
病理学
儿科学
周围血管疾病
药理学和药剂学
生理学
基本医疗保健
精神病学
公共、环境和职业卫生
放射学,核医学和医学成像
康复学
生殖生物学
呼吸系统
风湿病学
运动科学
外科学
毒理学
热带医学
泌尿学和肾脏学
病毒学
老年医学
健康政策和服务
心理学,临床
abstract::Predictably regulating protein expression levels to improve recombinant protein production has become an important tool, but is still rarely applied to engineer mammalian cells. We therefore sought to set-up an easy-to-implement toolbox to facilitate fast and reliable regulation of protein expression in mammalian cell...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa847
更新日期:2020-11-18 00:00:00
abstract::HORMA domain-containing proteins (HORMADs) play an essential role in meiosis in many organisms. The meiotic HORMADs, including yeast Hop1, mouse HORMAD1 and HORMAD2, and Arabidopsis ASY1, assemble along chromosomes at early prophase and the closure motif at their C-termini has been hypothesized to be instrumental for ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa527
更新日期:2020-11-18 00:00:00
abstract::Double-stranded DNA viruses use ATP-powered molecular motors to package their genomic DNA. To ensure efficient genome encapsidation, these motors regulate functional transitions between initiation, translocation, and termination modes. Here, we report structural and biophysical analyses of the C-terminal domain of the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa874
更新日期:2020-11-18 00:00:00
abstract::Mismatch repair is a highly conserved cellular pathway responsible for repairing mismatched dsDNA. Errors are detected by the MutS enzyme, which most likely senses altered mechanical property of damaged dsDNA rather than a specific molecular pattern. While the curved shape of dsDNA in crystallographic MutS/DNA structu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa896
更新日期:2020-11-18 00:00:00
abstract::Studies of bacterial chromosomes and plasmids indicate that their replication initiator proteins bind to origins of replication at many double-stranded sites and also at AT-rich regions where single-stranded DNA is exposed during origin opening. Single-strand binding apparently promotes origin opening by stabilizing a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa826
更新日期:2020-11-04 00:00:00
abstract::Circular DNA aptamers are powerful candidates for therapeutic applications given their dramatically enhanced biostability. Herein we report the first effort to evolve circular DNA aptamers that bind a human protein directly in serum, a complex biofluid. Targeting human thrombin, this strategy has led to the discovery ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa800
更新日期:2020-11-04 00:00:00
abstract::ATR functions as a master regulator of the DNA-damage response. ATR activation requires the ATR activator, topoisomerase IIβ-binding protein 1 (TopBP1). However, the underlying mechanism of TopBP1 regulation and how its regulation affects DNA replication remain unknown. Here, we report a specific interaction between T...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa756
更新日期:2020-11-04 00:00:00
abstract::During DNA replication, the presence of 8-oxoguanine (8-oxoG) lesions in the template strand cause the high-fidelity (HiFi) DNA polymerase (Pol) to stall. An early response to 8-oxoG lesions involves 'on-the-fly' translesion synthesis (TLS), in which a specialized TLS Pol is recruited and replaces the stalled HiFi Pol...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa803
更新日期:2020-11-04 00:00:00
abstract::Horizontally acquired genes are typically regulated by ancestral regulators. This regulation enables expression of horizontally acquired genes to be coordinated with that of preexisting genes. Here, we report a singular example of the opposite regulation: a horizontally acquired gene that controls an ancestral regulat...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa813
更新日期:2020-11-04 00:00:00
abstract::Synonymous codon usage significantly impacts translational and transcriptional efficiency, gene expression, the secondary structure of both mRNA and proteins, and has been implicated in various diseases. However, population-specific differences in codon usage biases remain largely unexplored. Here, we present a web se...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa863
更新日期:2020-11-04 00:00:00
abstract::G-quadruplexes (G4s) are nucleic acid structure motifs that are of significance in chemistry and biology. The function of G4s is often governed by their interaction with G4-binding proteins. Few categories of G4-specific tools have been developed to inhibit G4-protein interactions; however, until now there is no aptam...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa759
更新日期:2020-10-09 00:00:00
abstract::The underlying mechanism of transcriptional co-repressor ETO2 during early erythropoiesis and hemoglobin switching is unclear. We find that absence of ETO2 in mice interferes with down-regulation of PU.1 and GATA2 in the fetal liver, impeding a key step required for commitment to erythroid maturation. In human β-globi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa736
更新日期:2020-10-09 00:00:00
abstract::A 5',7-methylguanosine cap is a quintessential feature of RNA polymerase II-transcribed RNAs, and a textbook aspect of co-transcriptional RNA processing. The cap is bound by the cap-binding complex (CBC), canonically consisting of nuclear cap-binding proteins 1 and 2 (NCBP1/2). Interest in the CBC has recently renewed...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa743
更新日期:2020-10-09 00:00:00
abstract::Poly(ADP-ribosyl)ation regulates numerous cellular processes like genome maintenance and cell death, thus providing protective functions but also contributing to several pathological conditions. Poly(ADP-ribose) (PAR) molecules exhibit a remarkable heterogeneity in chain lengths and branching frequencies, but the biol...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa590
更新日期:2020-10-09 00:00:00
abstract::To gain insight into the mechanistic link between translation termination and nonsense-mediated mRNA decay (NMD), we depleted the ribosome recycling factor ABCE1 in human cells, resulting in an upregulation of NMD-sensitive mRNAs. Suppression of NMD on these mRNAs occurs prior to their SMG6-mediated endonucleolytic cl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa758
更新日期:2020-10-09 00:00:00
abstract::The Xist lncRNA requires Repeat A, a conserved RNA element located in its 5' end, to induce gene silencing during X-chromosome inactivation. Intriguingly, Repeat A is also required for production of Xist. While silencing by Repeat A requires the protein SPEN, how Repeat A promotes Xist production remains unclear. We r...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa789
更新日期:2020-10-09 00:00:00
abstract::Stringent starvation protein A (SspA) is an RNA polymerase (RNAP)-associated protein involved in nucleotide metabolism, acid tolerance and virulence of bacteria. Despite extensive biochemical and genetic analyses, the precise regulatory role of SspA in transcription is still unknown, in part, because of a lack of stru...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa672
更新日期:2020-09-25 00:00:00
abstract::CTCF plays a pivotal role in mediating chromatin interactions, but it does not do so alone. A number of factors have been reported to co-localize with CTCF and regulate CTCF loops, but no comprehensive analysis of binding partners has been performed. This prompted us to identify CTCF loop participants and regulators b...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa705
更新日期:2020-09-25 00:00:00
abstract::RNA G-quadruplexes (G4s) are secondary structures proposed to function as regulators of post-transcriptional mRNA localisation and translation. G4s within some neuronal mRNAs are known to control distal localisation and local translation, contributing to distinct local proteomes that facilitate the synaptic remodellin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa699
更新日期:2020-09-25 00:00:00
abstract::Transcription termination defines accurate transcript 3'-ends and ensures programmed transcriptomes, making it critical to life. However, transcription termination mechanisms remain largely unknown in Archaea. Here, we reported the physiological significance of the newly identified general transcription termination fa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa702
更新日期:2020-09-25 00:00:00
abstract::Inducible promoters are a central regulatory component in synthetic biology, metabolic engineering, and protein production for laboratory and commercial uses. Many of these applications utilize two or more exogenous promoters, imposing a currently unquantifiable metabolic burden on the living system. Here, we engineer...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa734
更新日期:2020-09-25 00:00:00
abstract::We present NetCore, a novel network propagation approach based on node coreness, for phenotype-genotype associations and module identification. NetCore addresses the node degree bias in PPI networks by using node coreness in the random walk with restart procedure, and achieves improved re-ranking of genes after propag...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa639
更新日期:2020-09-25 00:00:00
abstract::Posttranslational modifications (PTMs) of histones represent a crucial regulatory mechanism of nucleosome and chromatin dynamics in various of DNA-based cellular processes, such as replication, transcription and DNA damage repair. Lysine succinylation (Ksucc) is a newly identified histone PTM, but its regulation and f...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa663
更新日期:2020-09-25 00:00:00
abstract::Stable protein complexes, including those formed with RNA, are major building blocks of every living cell. Escherichia coli has been the leading bacterial organism with respect to global protein-protein networks. Yet, there has been no global census of RNA/protein complexes in this model species of microbiology. Here,...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa676
更新日期:2020-09-18 00:00:00
abstract::The p53 transcription factor confers its potent tumor suppressor functions primarily through the regulation of a large network of target genes. The recent explosion of next generation sequencing protocols has enabled the study of the p53 gene regulatory network (GRN) and underlying mechanisms at an unprecedented depth...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa666
更新日期:2020-09-18 00:00:00
abstract::Gene losses provide an insightful route for studying the morphological and physiological adaptations of species, but their discovery is challenging. Existing genome annotation tools focus on annotating intact genes and do not attempt to distinguish nonfunctional genes from genes missing annotation due to sequencing an...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa550
更新日期:2020-09-18 00:00:00
abstract::We used the high resolution and accuracy of the Cambridge Structural Database (CSD) to provide detailed information regarding base pairing interactions of selected nucleobases. We searched for base pairs in which nucleobases interact with each other through two or more hydrogen bonds and form more or less planar struc...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa629
更新日期:2020-09-04 00:00:00
abstract::DNA synthesis is a fundamental requirement for cell proliferation and DNA repair, but no single method can identify the location, direction and speed of replication forks with high resolution. Mammalian cells have the ability to incorporate thymidine analogs along with the natural A, T, G and C bases during DNA synthe...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa517
更新日期:2020-09-04 00:00:00
abstract::H/ACA small nucleolar RNAs (snoRNAs) guide pseudouridylation as part of a small nucleolar ribonucleoprotein complex (snoRNP). Disruption of H/ACA snoRNA levels in stem cells impairs pluripotency, yet it remains unclear how H/ACA snoRNAs contribute to differentiation. To determine if H/ACA snoRNA levels are dynamic dur...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa612
更新日期:2020-09-04 00:00:00
abstract::Single-cell RNA-sequencing (scRNA-seq) enables the characterization of transcriptomic profiles at the single-cell resolution with increasingly high throughput. However, it suffers from many sources of technical noises, including insufficient mRNA molecules that lead to excess false zero values, termed dropouts. Comput...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa506
更新日期:2020-09-04 00:00:00
abstract::Highly toxic DNA double-strand breaks (DSBs) readily trigger the DNA damage response (DDR) in cells, which delays cell cycle progression to ensure proper DSB repair. In Saccharomyces cerevisiae, mitotic S phase (20-30 min) is lengthened upon DNA damage. During meiosis, Spo11-induced DSB onset and repair lasts up to 5 ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa587
更新日期:2020-09-04 00:00:00
abstract::Alternative splicing (AS) and alternative polyadenylation (APA) generate diverse transcripts in mammalian genomes during development and differentiation. Epigenetic marks such as trimethylation of histone H3 lysine 36 (H3K36me3) and DNA methylation play a role in generating transcriptome diversity. Intragenic CpG isla...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa556
更新日期:2020-09-04 00:00:00
abstract::Specific nucleic acid sequences can be detected in individual cells by in situ hybridization. However, when very few copies of a target sequence are present per cell, its signal is undetectable by flow cytometry. Although various approaches have been developed to increase fluorescence signals for in situ hybridization...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa515
更新日期:2020-09-04 00:00:00
abstract::Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa545
更新日期:2020-08-20 00:00:00
abstract::In synthetic circuits, CRISPR-Cas systems have been used effectively for endpoint changes from an initial state to a final state, such as in logic gates. Here, we use deactivated Cas9 (dCas9) and deactivated Cas12a (dCas12a) to construct dynamic RNA ring oscillators that cycle continuously between states over time in ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa557
更新日期:2020-08-20 00:00:00
abstract::Allostery is comprehensively studied for natural macromolecules, such as proteins and nucleic acids. Here, we present controllable allostery of synthetic DNA nanostructure-enzyme systems. Rational designs of the synthetic allosteric systems are based on an in-depth understanding of allosteric sites with several types ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa488
更新日期:2020-07-27 00:00:00
abstract::Methylation of miRNAs at the 2'-hydroxyl group on the ribose at 3'-end (2'-O-methylation, 2'Ome) is critical for miRNA function in plants and Drosophila. Whether this methylation phenomenon exists for mammalian miRNA remains unknown. Through LC-MS/MS analysis, we discover that majority of miR-21-5p isolated from human...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa504
更新日期:2020-07-27 00:00:00
abstract::The modulation of GLI2, an oncogenic transcription factor commonly upregulated in cancer, is in many cases not due to genetic defects, suggesting dysregulation through alternative mechanisms. The identity of these molecular events remains for the most part unknown. Here, we identified TFII-I as a novel repressor of GL...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa476
更新日期:2020-07-27 00:00:00
abstract::Despite two decades of study, the full scope of RNAi in mammalian cells has remained obscure. Here we combine: (i) Knockout of argonaute (AGO) variants; (ii) RNA sequencing analysis of gene expression changes and (iii) Enhanced Crosslinking Immunoprecipitation Sequencing (eCLIP-seq) using anti-AGO2 antibody to identif...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa478
更新日期:2020-07-27 00:00:00
abstract::Digital PCR provides high sensitivity and unprecedented accuracy in DNA quantification, but current approaches require dedicated instrumentation and have limited opportunities for multiplexing. Here, we present an isothermal platform for digital enumeration of DNA reaction products in multiplex via standard fluorescen...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa419
更新日期:2020-07-27 00:00:00