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::Regulation of food intake is fundamental to energy homeostasis in animals. The contribution of non-nutritive and metabolic signals in regulating feeding is unclear. Here we show that enteric neurons play a major role in regulating feeding through specialized mechanosensory ion channels in Drosophila. Modulating activi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04402
更新日期:2014-10-06 00:00:00
abstract::Plasma membrane lipid composition must be maintained during growth and under environmental insult. In yeast, signaling mediated by TOR Complex 2 (TORC2)-dependent protein kinase Ypk1 controls lipid abundance and distribution in response to membrane stress. Ypk1, among other actions, alleviates negative regulation of L...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03779
更新日期:2014-10-03 00:00:00
abstract::The TAM receptor tyrosine kinases Tyro3, Axl, and Mer regulate key features of cellular physiology, yet the differential activities of the TAM ligands Gas6 and Protein S are poorly understood. We have used biochemical and genetic analyses to delineate the rules for TAM receptor-ligand engagement and find that the TAMs...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03385
更新日期:2014-09-29 00:00:00
abstract::The receptor protein Dectin-1 recognizes structures found on cancerous cells, and then triggers an anti-tumor immune response. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.04476
更新日期:2014-09-24 00:00:00
abstract::Faithful chromosome segregation in all eukaryotes relies on centromeres, the chromosomal sites that recruit kinetochore proteins and mediate spindle attachment during cell division. The centromeric histone H3 variant, CenH3, is the defining chromatin component of centromeres in most eukaryotes, including animals, fung...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03676
更新日期:2014-09-23 00:00:00
abstract::During development, tissue repair, and tumor growth, most blood vessel networks are generated through angiogenesis. Vascular endothelial growth factor (VEGF) is a key regulator of this process and currently both VEGF and its receptors, VEGFR1, VEGFR2, and Neuropilin1 (NRP1), are targeted in therapeutic strategies for ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03720
更新日期:2014-09-22 00:00:00
abstract::Membrane transporters of the RND superfamily confer multidrug resistance to pathogenic bacteria, and are essential for cholesterol metabolism and embryonic development in humans. We use high-resolution X-ray crystallography and computational methods to delineate the mechanism of the homotrimeric RND-type proton/drug a...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03145
更新日期:2014-09-19 00:00:00
abstract::Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03781
更新日期:2014-09-12 00:00:00
abstract::Cells can avoid the effects of so-called 'nonsense' mutations by several methods, including a newly discovered mechanism driven by microRNA molecules. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.04300
更新日期:2014-09-09 00:00:00
abstract::During inflammation, serum amyloid A proteins transport retinol to infected tissues. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.04246
更新日期:2014-09-02 00:00:00
abstract::Lamina-associated polypeptide 1 (LAP1) resides at the nuclear envelope and interacts with Torsins, poorly understood endoplasmic reticulum (ER)-localized AAA+ ATPases, through a conserved, perinuclear domain. We determined the crystal structure of the perinuclear domain of human LAP1. LAP1 possesses an atypical AAA+ f...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03239
更新日期:2014-08-22 00:00:00
abstract::In all living organisms, ribosomes translating membrane proteins are targeted to membrane translocons early in translation, by the ubiquitous signal recognition particle (SRP) system. In eukaryotes, the SRP Alu domain arrests translation elongation of membrane proteins until targeting is complete. Curiously, however, ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03440
更新日期:2014-08-18 00:00:00
abstract::The Cdc45/Mcm2-7/GINS (CMG) helicase separates DNA strands during replication in eukaryotes. How the CMG is assembled and engages DNA substrates remains unclear. Using electron microscopy, we have determined the structure of the CMG in the presence of ATPγS and a DNA duplex bearing a 3' single-stranded tail. The struc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03273
更新日期:2014-08-12 00:00:00
abstract::The mechanisms generating epileptic neuronal networks following insults such as severe seizures are unknown. We have previously shown that interfering with the function of the neuron-restrictive silencer factor (NRSF/REST), an important transcription factor that influences neuronal phenotype, attenuated development of...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01267
更新日期:2014-08-12 00:00:00
abstract::Even when we are at rest, our spinal cords show spontaneous, yet well organised, fluctuations of activity that might reflect sensory and motor networks. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.03811
更新日期:2014-08-05 00:00:00
abstract::Calcineurin is responsible for mediating a wide variety of cellular processes in response to dynamic calcium (Ca(2+)) signals, yet the precise mechanisms involved in the spatiotemporal control of calcineurin signaling are poorly understood. Here, we use genetically encoded fluorescent biosensors to directly probe the ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03765
更新日期:2014-07-23 00:00:00
abstract::Temperature-sensitive transient receptor potential (TRP) ion channels are members of the large tetrameric cation channels superfamily but are considered to be uniquely sensitive to heat, which has been presumed to be due to the existence of an unidentified temperature-sensing domain. Here we report that the homologous...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03255
更新日期:2014-07-16 00:00:00
abstract::To understand the neural origins of rhythmic behavior one must characterize the central pattern generator circuit and quantify the population size needed to sustain functionality. Breathing-related interneurons of the brainstem pre-Bötzinger complex (preBötC) that putatively comprise the core respiratory rhythm genera...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03427
更新日期:2014-07-15 00:00:00
abstract::New data on the relationship between two proteins, cyclin D and Rb, suggest that we need to re-evaluate our understanding of how cells enter into the cell cycle. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.03475
更新日期:2014-07-01 00:00:00
abstract::Hybrid sterility is one of the earliest postzygotic isolating mechanisms to evolve between two recently diverged species. Here we identify causes underlying hybrid infertility of two recently diverged fission yeast species Schizosaccharomyces pombe and S. kambucha, which mate to form viable hybrid diploids that effici...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02630
更新日期:2014-06-24 00:00:00
abstract::Recent studies suggested an essential role for seryl-tRNA synthetase (SerRS) in vascular development. This role is specific to SerRS among all tRNA synthetases and is independent of its well-known aminoacylation function in protein synthesis. A unique nucleus-directing domain, added at the invertebrate-to-vertebrate t...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02349
更新日期:2014-06-17 00:00:00
abstract::Cell surface reception of Sonic hedgehog (Shh) must ensure that the graded morphogenic signal is interpreted accordingly in neighboring cells to specify tissue patterns during development. Here, we report endocytic sorting signals for the receptor Patched1 (Ptch1), comprising two 'PPXY' motifs, that direct it to degra...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02555
更新日期:2014-06-12 00:00:00
abstract::Individuals vary in their responses to stroke and trauma, hampering predictions of outcomes. One reason might be that neural circuits contain hidden variability that becomes relevant only when those individuals are challenged by injury. We found that in the mollusc, Tritonia diomedea, subtle differences between animal...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02598
更新日期:2014-06-11 00:00:00
abstract::Although the wiring of the cerebellar cortex appears to be uniform, the neurons in this region of the brain behave more differently from each other than previously thought. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.03285
更新日期:2014-06-10 00:00:00
abstract::A major puzzle in biology is how mammalian sperm maintain the correct swimming direction during various phases of the sexual reproduction process. Whilst chemotaxis may dominate near the ovum, it is unclear which cues guide spermatozoa on their long journey towards the egg. Hypothesized mechanisms range from peristalt...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02403
更新日期:2014-05-27 00:00:00
abstract::Recent epidemiological and laboratory-based studies suggest that the anti-diabetic drug metformin prevents cancer progression. How metformin diminishes tumor growth is not fully understood. In this study, we report that in human cancer cells, metformin inhibits mitochondrial complex I (NADH dehydrogenase) activity and...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02242
更新日期:2014-05-13 00:00:00
abstract::During translation elongation, the ribosome ratchets along its mRNA template, incorporating each new amino acid and translocating from one codon to the next. The elongation cycle requires dramatic structural rearrangements of the ribosome. We show here that deep sequencing of ribosome-protected mRNA fragments reveals ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01257
更新日期:2014-05-09 00:00:00
abstract::Atopic dermatitis can result from loss of structural proteins in the outermost epidermal layers, leading to a defective epidermal barrier. To test whether this influences tumour formation, we chemically induced tumours in EPI-/- mice, which lack three barrier proteins-Envoplakin, Periplakin, and Involucrin. EPI-/- mic...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01888
更新日期:2014-05-05 00:00:00
abstract::Homologous recombination (HR)-mediated repair of DNA double-strand break (DSB)s is restricted to the post-replicative phases of the cell cycle. Initiation of HR in the G1 phase blocks non-homologous end joining (NHEJ) impairing DSB repair. Completion of HR in G1 cells can lead to the loss-of-heterozygosity (LOH), whic...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02445
更新日期:2014-04-30 00:00:00
abstract::Hox genes are essential regulators of embryonic development. Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products. We have analyzed the 3D chromatin organization of Hox clusters ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02557
更新日期:2014-04-29 00:00:00
abstract::Cerebellar climbing fiber activity encodes performance errors during many motor learning tasks, but the role of these error signals in learning has been controversial. We compared two motor learning paradigms that elicited equally robust putative error signals in the same climbing fibers: learned increases and decreas...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02076
更新日期:2014-04-22 00:00:00
abstract::Chronic endoplasmic reticulum (ER) stress results in toxicity that contributes to multiple human disorders. We report a stress resolution pathway initiated by the nuclear receptor LRH-1 that is independent of known unfolded protein response (UPR) pathways. Like mice lacking primary UPR components, hepatic Lrh-1-null m...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01694
更新日期:2014-04-15 00:00:00
abstract::When a plant cell divides, four related proteins control the trafficking of vesicles and ensure that cargo that is normally recycled to the plasma membrane is instead re-routed to the plane of cell division. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.02747
更新日期:2014-04-08 00:00:00
abstract::Neuropathic pain remains notoriously difficult to treat despite numerous drug targets. Here, we offer a novel explanation for this intractability. Computer simulations predicted that qualitative changes in primary afferent excitability linked to neuropathic pain arise through a switch in spike initiation dynamics when...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02370
更新日期:2014-04-01 00:00:00
abstract::Many primary sensory cilia exhibit unique architectures that are critical for transduction of specific sensory stimuli. Although basic ciliogenic mechanisms are well described, how complex ciliary structures are generated remains unclear. Seminal work performed several decades ago provided an initial but incomplete de...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01948
更新日期:2014-03-25 00:00:00
abstract::Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior-posterior axis. Hox proteins exert their function by interaction wit...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01939
更新日期:2014-03-18 00:00:00
abstract::Stem cells are maintained in a specialized microenvironment called niche but the nature of stem cell niche remains poorly defined in many systems. Here we demonstrate that intestinal epithelium-derived BMP serves as a niche signal for intestinal stem cell (ISC) self-renewal in Drosophila adult midgut. We find that BMP...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01857
更新日期:2014-03-11 00:00:00
abstract::Bacterial flagella mediate host-microbe interactions through tissue tropism during colonization, as well as by activating immune responses. The flagellar shaft of some bacteria, including several human pathogens, is encased in a membranous sheath of unknown function. While it has been hypothesized that the sheath may ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01579
更新日期:2014-03-04 00:00:00
abstract::Microtubule dynamics facilitate neurite growth and establish morphology, but the role of minus-end binding proteins in these processes is largely unexplored. CAMSAP homologs associate with microtubule minus-ends, and are important for the stability of epithelial cell adhesions. In this study, we report morphological d...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01637
更新日期:2014-02-25 00:00:00
abstract::Orphans are genes restricted to a single phylogenetic lineage and emerge at high rates. While this predicts an accumulation of genes, the gene number has remained remarkably constant through evolution. This paradox has not yet been resolved. Because orphan genes have been mainly analyzed over long evolutionary time sc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01311
更新日期:2014-02-19 00:00:00