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::A well-established cascade of transcription factor (TF) activity orchestrates adipogenesis in response to chemical cues, yet how cell-intrinsic determinants of differentiation such as cell shape and/or seeding density inform this transcriptional program remain enigmatic. Here, we uncover a novel mechanism licensing tr...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.06821
更新日期:2015-06-25 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving cytotoxic conformations of Cu, Zn superoxide dismutase (SOD1). A major challenge in understanding ALS disease pathology has been the identification and atomic-level characterization of these conformers. Here, we use a combination ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.07296
更新日期:2015-06-23 00:00:00
abstract::Gustatory pheromones play an essential role in shaping the behavior of many organisms. However, little is known about the processing of taste pheromones in higher order brain centers. Here, we describe a male-specific gustatory circuit in Drosophila that underlies the detection of the anti-aphrodisiac pheromone (3R,11...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.06914
更新日期:2015-06-17 00:00:00
abstract::Pervasive expression of circular RNA is a recently discovered feature of eukaryotic gene expression programs, yet its function remains largely unknown. The presumed biogenesis of these RNAs involves a non-canonical 'backsplicing' event. Recent studies in mammalian cell culture posit that backsplicing is facilitated by...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.07540
更新日期:2015-06-09 00:00:00
abstract::Striatal dysfunction plays an important role in dystonia, but the striatal cell types that contribute to abnormal movements are poorly defined. We demonstrate that conditional deletion of the DYT1 dystonia protein torsinA in embryonic progenitors of forebrain cholinergic and GABAergic neurons causes dystonic-like twis...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.08352
更新日期:2015-06-08 00:00:00
abstract::Centrioles are microtubule-based organelles crucial for cell division, sensing and motility. In Caenorhabditis elegans, the onset of centriole formation requires notably the proteins SAS-5 and SAS-6, which have functional equivalents across eukaryotic evolution. Whereas the molecular architecture of SAS-6 and its role...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.07410
更新日期:2015-05-29 00:00:00
abstract::The neural correlates of consciousness are typically sought by comparing the overall brain responses to perceived and unperceived stimuli. However, this comparison may be contaminated by non-specific attention, alerting, performance, and reporting confounds. Here, we pursue a novel approach, tracking the neuronal codi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05652
更新日期:2015-05-21 00:00:00
abstract::The final identity of a differentiated neuron is determined by multiple signaling events, including activity dependent calcium transients. Non-canonical Frizzled2 (Fz2) signaling generates calcium transients that determine neuronal polarity, neuronal migration, and synapse assembly in the developing vertebrate brain. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.07046
更新日期:2015-05-08 00:00:00
abstract::The time it takes a sound to travel from source to ear differs between the ears and creates an interaural delay. It varies systematically with spatial direction and is generally modeled as a pure time delay, independent of frequency. In acoustical recordings, we found that interaural delay varies with frequency at a f...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.06072
更新日期:2015-04-27 00:00:00
abstract::Adipocyte differentiation is a strictly controlled process regulated by a series of transcriptional activators. Adipogenic signals activate early adipogenic activators and facilitate the transient formation of early enhanceosomes at target genes. These enhancer regions are subsequently inherited by late enhanceosomes....
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05615
更新日期:2015-04-23 00:00:00
abstract::In the retina, synaptic transmission between photoreceptors and downstream ON-bipolar neurons (ON-BCs) is mediated by a GPCR pathway, which plays an essential role in vision. However, the mechanisms that control signal transmission at this synapse and its relevance to behavior remain poorly understood. In this study w...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.06358
更新日期:2015-04-16 00:00:00
abstract::Numerous brain regions have been shown to have neural correlates of gradually accumulating evidence for decision-making, but the causal roles of these regions in decisions driven by accumulation of evidence have yet to be determined. Here, in rats performing an auditory evidence accumulation task, we inactivated the f...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05457
更新日期:2015-04-14 00:00:00
abstract::Here, we document a collection of ∼7434 MiMIC (Minos Mediated Integration Cassette) insertions of which 2854 are inserted in coding introns. They allowed us to create a library of 400 GFP-tagged genes. We show that 72% of internally tagged proteins are functional, and that more than 90% can be imaged in unfixed tissue...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05338
更新日期:2015-03-31 00:00:00
abstract::Toothed whales use sonar to detect, locate, and track prey. They adjust emitted sound intensity, auditory sensitivity and click rate to target range, and terminate prey pursuits with high-repetition-rate, low-intensity buzzes. However, their narrow acoustic field of view (FOV) is considered stable throughout target ap...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05651
更新日期:2015-03-20 00:00:00
abstract::Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP. Surprisingly, PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate selec...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04871
更新日期:2015-03-16 00:00:00
abstract::The circadian transcriptional repressors cryptochrome 1 (Cry1) and 2 (Cry2) evolved from photolyases, bacterial light-activated DNA repair enzymes. In this study, we report that while they have lost DNA repair activity, Cry1/2 adapted to protect genomic integrity by responding to DNA damage through posttranslational m...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04883
更新日期:2015-03-10 00:00:00
abstract::In eukaryotes, most integral membrane proteins are synthesized, integrated into the membrane, and folded properly in the endoplasmic reticulum (ER). We screened the mutants affecting rhabdomeric expression of rhodopsin 1 (Rh1) in the Drosophila photoreceptors and found that dPob/EMC3, EMC1, and EMC8/9, Drosophila homo...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.06306
更新日期:2015-02-26 00:00:00
abstract::Loss of polarity correlates with progression of epithelial cancers, but how plasma membrane misorganization drives oncogenic transcriptional events remains unclear. The polarity regulators of the Drosophila Scribble (Scrib) module are potent tumor suppressors and provide a model for mechanistic investigation. RNA prof...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03189
更新日期:2015-02-26 00:00:00
abstract::Previously, we identified ISRIB as a potent inhibitor of the integrated stress response (ISR) and showed that ISRIB makes cells resistant to the effects of eIF2α phosphorylation and enhances long-term memory in rodents (Sidrauski et al., 2013). Here, we show by genome-wide in vivo ribosome profiling that translation o...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05033
更新日期:2015-02-26 00:00:00
abstract::During outbreaks of high-consequence pathogens, airport screening programs have been deployed to curtail geographic spread of infection. The effectiveness of screening depends on several factors, including pathogen natural history and epidemiology, human behavior, and characteristics of the source epidemic. We develop...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05564
更新日期:2015-02-19 00:00:00
abstract::Armor plate changes in sticklebacks are a classic example of repeated adaptive evolution. Previous studies identified ectodysplasin (EDA) gene as the major locus controlling recurrent plate loss in freshwater fish, though the causative DNA alterations were not known. Here we show that freshwater EDA alleles have cis-a...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05290
更新日期:2015-01-28 00:00:00
abstract::Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exh...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04494
更新日期:2015-01-20 00:00:00
abstract::Cell fate decisions are critical for life, yet little is known about how their reliability is achieved when signals are noisy and fluctuating with time. In this study, we show that in budding yeast, the decision of cell cycle commitment (Start) is determined by the time integration of its triggering signal Cln3. We fu...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03977
更新日期:2015-01-14 00:00:00
abstract::Heterochromatin exerts a heritable form of eukaryotic gene repression and contributes to chromosome segregation fidelity and genome stability. However, to date there has been no quantitative evaluation of the stability of heterochromatic gene repression. We designed a genetic strategy to capture transient losses of ge...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05007
更新日期:2015-01-12 00:00:00
abstract::Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle, limiting their use in physiological and pharmacological studies. Here, we demonstrate engineering of electrically and chemically responsive, contractile human muscle tissues ('myobundles') using primar...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04885
更新日期:2015-01-09 00:00:00
abstract::miR-128, a brain-enriched microRNA, has been implicated in the control of neurogenesis and synaptogenesis but its potential roles in intervening processes have not been addressed. We show that post-transcriptional mechanisms restrict miR-128 accumulation to post-mitotic neurons during mouse corticogenesis and in adult...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04263
更新日期:2015-01-03 00:00:00
abstract::Actin, spectrin, and associated molecules form a periodic sub-membrane lattice structure in axons. How this membrane skeleton is developed and why it preferentially forms in axons are unknown. Here, we studied the developmental mechanism of this lattice structure. We found that this structure emerged early during axon...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04581
更新日期:2014-12-23 00:00:00
abstract::In order to assess the contribution of a central clock in the hypothalamic suprachiasmatic nucleus (SCN) to circadian behavior and the organization of peripheral clocks, we generated forebrain/SCN-specific Bmal1 knockout mice by using floxed Bmal1 and pan-neuronal Cre lines. The forebrain knockout mice showed >90% del...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04617
更新日期:2014-12-19 00:00:00
abstract::How different helicase families with a conserved catalytic 'helicase core' evolved to function on varied RNA and DNA substrates by diverse mechanisms remains unclear. In this study, we used Mss116, a yeast DEAD-box protein that utilizes ATP to locally unwind dsRNA, to investigate helicase specificity and mechanism. Ou...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04630
更新日期:2014-12-12 00:00:00
abstract::Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest know...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03743
更新日期:2014-12-11 00:00:00
abstract::Drosophila larvae and adults possess a potent innate immune response, but the response of Drosophila eggs is poor. In contrast to Drosophila, eggs of the beetle Tribolium are protected by a serosa, an extraembryonic epithelium that is present in all insects except higher flies. In this study, we test a possible immune...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04111
更新日期:2014-12-09 00:00:00
abstract::Dorsal/ventral (DV) patterning of the sea urchin embryo relies on a ventrally-localized organizer expressing Nodal, a pivotal regulator of the DV gene regulatory network. However, the inceptive mechanisms imposing the symmetry-breaking are incompletely understood. In Paracentrotus lividus, the Hbox12 homeodomain-conta...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04664
更新日期:2014-12-02 00:00:00
abstract::Acquisition of pluripotency is driven largely at the transcriptional level by activators OCT4, SOX2, and NANOG that must in turn cooperate with diverse coactivators to execute stem cell-specific gene expression programs. Using a biochemically defined in vitro transcription system that mediates OCT4/SOX2 and coactivato...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03573
更新日期:2014-11-19 00:00:00
abstract::In eukaryotes, intra-chromosomal recombination generates DNA circles, but little is known about how cells react to them. In yeast, partitioning of such circles to the mother cell at mitosis ensures their loss from the population but promotes replicative ageing. Nevertheless, the mechanisms of partitioning are debated....
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03790
更新日期:2014-11-17 00:00:00
abstract::Entry and extrusion of cations are essential processes in living cells. In alkaliphilic prokaryotes, high external pH activates voltage-gated sodium channels (Nav), which allows Na(+) to enter and be used as substrate for cation/proton antiporters responsible for cytoplasmic pH homeostasis. Here, we describe a new mem...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04387
更新日期:2014-11-11 00:00:00
abstract::In the developing fruit fly brain, a protein called Trithorax increases the number of neural cells produced from a single stem cell, in part by regulating the transcription of the target genes buttonhead and pointed. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05000
更新日期:2014-11-06 00:00:00
abstract::Humans and other animals routinely identify and attend to sensory stimuli so as to rapidly acquire rewards or avoid aversive experiences. Emotional arousal, a process mediated by the amygdala, can enhance attention to stimuli in a non-spatial manner. However, amygdala neural activity was recently shown to encode spati...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04478
更新日期:2014-10-30 00:00:00
abstract::Fruit fly neuroblasts can either self-renew, rest or take on a specialized form, depending on the levels of a protein called Prospero. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04869
更新日期:2014-10-29 00:00:00
abstract::Human SEMAPHORIN 5A (SEMA5A) is an autism susceptibility gene; however, its function in brain development is unknown. In this study, we show that mouse Sema5A negatively regulates synaptogenesis in early, developmentally born, hippocampal dentate granule cells (GCs). Sema5A is strongly expressed by GCs and regulates d...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04390
更新日期:2014-10-14 00:00:00
abstract::Innate lymphoid cells (ILCs) are recently identified lymphocytes that limit infection and promote tissue repair at mucosal surfaces. However, the pathways underlying ILC development remain unclear. Here we show that the transcription factor NFIL3 directs the development of a committed bone marrow precursor that differ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04406
更新日期:2014-10-13 00:00:00