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::Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.302679.117
更新日期:2017-08-15 00:00:00
abstract::Transcription is often stochastic. This is seemingly incompatible with the importance of gene expression during development. Here we show that during zebrafish embryogenesis, transcription activation is stochastic due to (1) genes acquiring transcriptional competence at different times in different cells, (2) differen...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.302935.117
更新日期:2017-08-15 00:00:00
abstract::Protection of the stalled replication fork is crucial for responding to replication stress and minimizing its impact on chromosome instability, thus preventing diseases, including cancer. We found a new component, Abro1, in the protection of stalled replication fork integrity. Abro1 deficiency results in increased chr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.299172.117
更新日期:2017-07-15 00:00:00
abstract::While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of mi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.303537.117
更新日期:2017-07-15 00:00:00
abstract::Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To determine the biological function of FDXR, we generated a Fdxr-deficient mouse model and found that loss of Fdxr led to embryonic lethality potentially due to ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.299388.117
更新日期:2017-06-15 00:00:00
abstract::Multiple DNA repair pathways maintain genome stability and ensure that DNA remains essentially unchanged over the life of a cell. Various human diseases occur if DNA repair is compromised, and most of these impact the nervous system, in some cases exclusively. However, it is often unclear what specific endogenous dama...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.301325.117
更新日期:2017-06-15 00:00:00
abstract::Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.302067.117
更新日期:2017-06-01 00:00:00
abstract::Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (C...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.297135.117
更新日期:2017-05-15 00:00:00
abstract::Long understood as a bona fide tumor suppressor that safeguards the integrity of the genome via regulating numerous cellular outcomes, p53 may also exert its decisive and versatile functions by controlling DNA methylation. In this issue of Genes & Development, Tovy and colleagues (pp. 959-972) report that, in naïve mo...
journal_title:Genes & development
pub_type: 评论,杂志文章,评审
doi:10.1101/gad.302364.117
更新日期:2017-05-15 00:00:00
abstract::DNA methylation is a key regulator of embryonic stem cell (ESC) biology, dynamically changing between naïve, primed, and differentiated states. The p53 tumor suppressor is a pivotal guardian of genomic stability, but its contributions to epigenetic regulation and stem cell biology are less explored. We report that, in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.299198.117
更新日期:2017-05-15 00:00:00
abstract::Telomeres are specialized nucleoprotein structures that protect chromosome ends from DNA damage response (DDR) and DNA rearrangements. The telomeric shelterin protein TRF2 suppresses the DDR, and this function has been attributed to its abilities to trigger t-loop formation or prevent massive decompaction and loss of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.294082.116
更新日期:2017-03-15 00:00:00
abstract::The female mammary gland is a very dynamic organ that undergoes continuous tissue remodeling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy (in this case transiently) increase the risk of breast cancer, the reasons are unclear. Growing clinical and experimental evid...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.292318.116
更新日期:2017-03-15 00:00:00
abstract::We hypothesized that basic helix-loop-helix (bHLH) MIST1 (BHLHA15) is a "scaling factor" that universally establishes secretory morphology in cells that perform regulated secretion. Here, we show that targeted deletion of MIST1 caused dismantling of the secretory apparatus of diverse exocrine cells. Parietal cells (PC...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.285684.116
更新日期:2017-01-15 00:00:00
abstract::The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. The identity of native adipocyte precursors has remained unclear...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.293704.116
更新日期:2017-01-15 00:00:00
abstract::Programmed cell death occurs in a highly reproducible manner during Caenorhabditis elegans development. We demonstrate that, during embryogenesis, miR-35 and miR-58 bantam family microRNAs (miRNAs) cooperate to prevent the precocious death of mothers of cells programmed to die by repressing the gene egl-1, which encod...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.288555.116
更新日期:2017-01-15 00:00:00
abstract::In many eukaryotes, siRNAs bound to Argonaute proteins guide chromatin-modifying enzymes to complementary loci, resulting in transcriptional gene silencing. Multiple lines of evidence indicate that siRNAs base-pair with longer RNAs produced at target loci, but the possibility that siRNAs base-pair directly with DNA re...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.294900.116
更新日期:2016-12-15 00:00:00
abstract::In cytoplasm, the survival of motor neuron (SMN) complex delivers pre-small nuclear RNAs (pre-snRNAs) to the heptameric Sm ring for the assembly of the ring complex on pre-snRNAs at the conserved Sm site [A(U)4-6G]. Gemin5, a WD40 protein component of the SMN complex, is responsible for recognizing pre-snRNAs. In addi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.288340.116
更新日期:2016-11-01 00:00:00
abstract::Oncogene-induced senescence (OIS) is a potent tumor suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.286112.116
更新日期:2016-10-01 00:00:00
abstract::Glucocorticoid (GC) receptor (GR) has been shown recently to bind a subset of mRNAs and elicit rapid mRNA degradation. However, the molecular details of GR-mediated mRNA decay (GMD) remain unclear. Here, we demonstrate that GMD triggers rapid degradation of target mRNAs in a translation-independent and exon junction c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.286484.116
更新日期:2016-09-15 00:00:00
abstract::Two broad gene classes are distinguished within multicellular organisms: cell type-specific genes, which confer particular cellular properties, and ubiquitous genes that support general cellular functions. However, certain so-called ubiquitous genes show functionally relevant cell type-specific repression. How such re...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.287904.116
更新日期:2016-09-15 00:00:00
abstract::The discovery of transcription factors (TFs) controlling pathways in health and disease is of paramount interest. We designed a widely applicable method, dubbed barcorded synthetic tandem repeat promoter screening (BC-STAR-PROM), to identify signal-activated TFs without any a priori knowledge about their properties. T...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.284828.116
更新日期:2016-08-15 00:00:00
abstract::The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a tran...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.284729.116
更新日期:2016-08-15 00:00:00
abstract::Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.281030.116
更新日期:2016-08-01 00:00:00
abstract::In Drosophila germ cells, PIWI-interacting RNAs (piRNAs) are amplified through a PIWI slicer-dependent feed-forward loop termed the ping-pong cycle, yielding secondary piRNAs. However, the detailed mechanism remains poorly understood, largely because an ex vivo model system amenable to biochemical analyses has not bee...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.283929.116
更新日期:2016-07-15 00:00:00
abstract::In this issue of Genes & Development, Dowen and colleagues (pp. 1515-1528) elegantly unify two previously unconnected aspects of physiology. The investigators provide significant genetic evidence to support a critical link between developmental timing decisions and the regulation of lipid mobilization at the transitio...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.285460.116
更新日期:2016-07-01 00:00:00
abstract::Nuclear pore complexes (NPCs) emerged as nuclear transport channels in eukaryotic cells ∼1.5 billion years ago. While the primary role of NPCs is to regulate nucleo-cytoplasmic transport, recent research suggests that certain NPC proteins have additionally acquired the role of affecting gene expression at the nuclear ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.280941.116
更新日期:2016-05-15 00:00:00
abstract::Cytosolic RNA/DNA sensing elicits primary defense against viral pathogens. Interferon regulatory factor 3 (IRF3), a key signal mediator/transcriptional factor of the antiviral-sensing pathway, is indispensible for interferon production and antiviral defense. However, how the status of IRF3 activation is controlled rem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.277533.116
更新日期:2016-05-01 00:00:00
abstract::The recombination-activating gene 1 (RAG1) and RAG2 proteins initiate V(D)J recombination, the process that assembles the B- and T-lymphocyte antigen receptor genes of jawed vertebrates. RAG1 and RAG2 are thought to have arisen from a transposable element, but the origins of this element are not understood. We show th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.278432.116
更新日期:2016-04-15 00:00:00
abstract::The eukaryotic ribosomal RNA (rRNA) is associated cotranscriptionally with numerous factors into an enormous 90S preribosomal particle that conducts early processing of small ribosomal subunits. The assembly pathway and structure of the 90S particle is poorly understood. Here, we affinity-purified and analyzed the con...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.274688.115
更新日期:2016-03-15 00:00:00
abstract::Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. Here we critically evaluate members of the SR protein family (SRSF1-7) for their potential to act as NXF1 adaptors that cou...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.276477.115
更新日期:2016-03-01 00:00:00
abstract::Metazoans start embryogenesis with a relatively naïve genome. The transcriptionally inert, late-replicating heterochromatic regions, including the constitutive heterochromatin on repetitive sequences near centromeres and telomeres, need to be re-established during development. To explore the events initiating heteroch...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.272237.115
更新日期:2016-03-01 00:00:00
abstract::Genome instability is a recurring feature of tumorigenesis. Mutation in MLL2, encoding a histone methyltransferase, is a driver in numerous different cancer types, but the mechanism is unclear. Here, we present evidence that MLL2 mutation results in genome instability. Mouse cells in which MLL2 gene deletion can be in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.275453.115
更新日期:2016-02-15 00:00:00
abstract::Animals alter their reproductive programs to accommodate changes in nutrient availability, yet the connections between known nutrient-sensing systems and reproductive programs are underexplored, and whether there is a mechanism that senses nucleotide levels to coordinate germline proliferation is unknown. We establish...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.275107.115
更新日期:2016-02-01 00:00:00
abstract::Class switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B-cell genome. Transcription at the immunoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transactivation domain-interact...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.268797.115
更新日期:2016-01-15 00:00:00
abstract::Reactive oxygen species (ROS) participate in numerous cell responses, including proliferation, DNA damage, and cell death. Based on these disparate activities, both promotion and inhibition of ROS have been proposed for cancer therapy. However, how the ROS response is determined is not clear. We examined the activitie...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271130.115
更新日期:2016-01-01 00:00:00
abstract::Genomic imprinting, an inherently epigenetic phenomenon defined by parent of origin-dependent gene expression, is observed in mammals and flowering plants. Genome-scale surveys of imprinted expression and the underlying differential epigenetic marks have led to the discovery of hundreds of imprinted plant genes and co...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.269902.115
更新日期:2015-12-15 00:00:00
abstract::The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an ∼ 500-residue N-terminal region, whose functions and mo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271528.115
更新日期:2015-12-15 00:00:00
abstract::Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271353.115
更新日期:2015-12-01 00:00:00
abstract::Alternative polyadenylation (APA) is widespread in neuronal development and activity-mediated neural plasticity. However, the underlying molecular mechanisms are largely unknown. We used systematic genetic studies and genome-wide surveys of the transcriptional landscape to identify a context-dependent regulatory pathw...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.266650.115
更新日期:2015-11-15 00:00:00
abstract::Mammalian cells possess two amino acid-sensing kinases: general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1). Their combined effects orchestrate cellular adaptation to amino acid levels, but how their activities are coordinated remains poorly understood. Here, we demonstrate...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.269324.115
更新日期:2015-11-15 00:00:00