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::Cystic Fibrosis (CF) is a monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in defective CFTR-mediated chloride and bicarbonate transport, with dysregulation of epithelial sodium channels (ENaC). These changes alter fluid and electrolyte homeostasis...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.49248
更新日期:2019-09-18 00:00:00
abstract::It is widely argued that personalized instruction based on individual differences in learning styles or genetic predispositions could improve learning outcomes. However, this proposition has resisted clear demonstration in human studies, where it is difficult to control experience and quantify outcomes. Here, we take ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47216
更新日期:2019-09-17 00:00:00
abstract::Motor fatigability emerges when demanding tasks are executed over an extended period of time. Here, we used repetitive low-force movements that cause a gradual reduction in movement speed (or 'motor slowing') to study the central component of fatigability in healthy adults. We show that motor slowing is associated wit...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46750
更新日期:2019-09-16 00:00:00
abstract::Single-molecule experiments reveal the dynamics of transcription through a nucleosome with single-base-pair accuracy. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.50761
更新日期:2019-09-13 00:00:00
abstract::Protein synthesis ends when a ribosome reaches an mRNA stop codon. Release factors (RFs) decode the stop codon, hydrolyze peptidyl-tRNA to release the nascent protein, and then dissociate to allow ribosome recycling. To visualize termination by RF2, we resolved a cryo-EM ensemble of E. coli 70S•RF2 structures at up to...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46850
更新日期:2019-09-12 00:00:00
abstract::How circuits assemble starting from stem cells is a fundamental question in developmental neurobiology. We test the hypothesis that, in neuronal stem cells, temporal transcription factors predictably control neuronal terminal features and circuit assembly. Using the Drosophila motor system, we manipulate expression of...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46089
更新日期:2019-09-10 00:00:00
abstract::Kinesin-1 and cytoplasmic dynein are microtubule (MT) motors that transport intracellular cargoes. It remains unclear how these motors move along MTs densely coated with obstacles of various sizes in the cytoplasm. Here, we tested the ability of single and multiple motors to bypass synthetic obstacles on MTs in vitro....
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.48629
更新日期:2019-09-09 00:00:00
abstract::Rhythmic events recruit neuronal activity in the basal ganglia and cerebellum, but their roles remain elusive. In monkeys attempting to detect a single omission of isochronous visual stimulus, we found that neurons in the caudate nucleus showed increased activity for each stimulus in sequence, while those in the cereb...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.48702
更新日期:2019-09-06 00:00:00
abstract::WW domain tandem-containing proteins such as KIBRA, YAP, and MAGI play critical roles in cell growth and polarity via binding to and positioning target proteins in specific subcellular regions. An immense disparity exists between promiscuity of WW domain-mediated target bindings and specific roles of WW domain protein...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.49439
更新日期:2019-09-05 00:00:00
abstract::Probabilistic models of adaptive immune repertoire sequence distributions can be used to infer the expansion of immune cells in response to stimulus, differentiate genetic from environmental factors that determine repertoire sharing, and evaluate the suitability of various target immune sequences for stimulation via v...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46935
更新日期:2019-09-05 00:00:00
abstract::The collapse of iconic, keystone populations of sockeye (Oncorhynchus nerka) and Chinook (Oncorhynchus tshawytscha) salmon in the Northeast Pacific is of great concern. It is thought that infectious disease may contribute to declines, but little is known about viruses endemic to Pacific salmon. Metatranscriptomic sequ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47615
更新日期:2019-09-03 00:00:00
abstract::Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-β-catenin, aldehyde dehydrogenase activities, intrinsic platinum resistance, and tumorsphere formation are here ass...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47327
更新日期:2019-09-03 00:00:00
abstract::Human lung adenocarcinoma exhibits a propensity for de-differentiation, complicating diagnosis and treatment, and predicting poorer patient survival. In genetically engineered mouse models of lung cancer, expression of the BRAFV600E oncoprotein kinase initiates the growth of benign tumors retaining characteristics of ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.43668
更新日期:2019-08-27 00:00:00
abstract::Upon detecting endoplasmic reticulum (ER) stress, the unfolded protein response (UPR) orchestrates adaptive cellular changes to reestablish homeostasis. If stress resolution fails, the UPR commits the cell to apoptotic death. Here we show that in hematopoietic cells, including multiple myeloma (MM), lymphoma, and leuk...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47084
更新日期:2019-08-27 00:00:00
abstract::Extracellular vesicles (EVs) encompass a variety of vesicles secreted into the extracellular space. EVs have been implicated in promoting tumor metastasis, but the molecular composition of tumor-derived EV sub-types and the mechanisms by which molecules are sorted into EVs remain mostly unknown. We report the separati...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47544
更新日期:2019-08-22 00:00:00
abstract::White adipose tissue (WAT) inflammation contributes to the development of insulin resistance in obesity. While the role of adipose tissue macrophage (ATM) pro-inflammatory signalling in the development of insulin resistance has been established, it is less clear how WAT inflammation is initiated. Here, we show that AT...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47990
更新日期:2019-08-16 00:00:00
abstract::The dorsal raphe nucleus (DRN) is an important source of neuromodulators and has been implicated in a wide variety of behavioral and neurological disorders. The DRN is subdivided into distinct anatomical subregions comprised of multiple cell types, and its complex cellular organization has impeded efforts to investiga...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46464
更新日期:2019-08-14 00:00:00
abstract::Knowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The c...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46681
更新日期:2019-08-12 00:00:00
abstract::Humans employ different strategies when making decisions. Previous research has reported reduced reliance on model-based strategies with aging, but it remains unclear whether this is due to cognitive or motivational factors. Moreover, it is not clear how aging affects the metacontrol of decision making, that is the dy...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.49154
更新日期:2019-08-09 00:00:00
abstract::Experience-dependent modifications of synaptic connections are thought to change patterns of network activities and stimulus tuning with learning. However, only a few studies explored how synaptic plasticity shapes the response dynamics of cortical circuits. Here, we investigated the mechanism underlying sharpening of...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.44098
更新日期:2019-08-08 00:00:00
abstract::Multiple sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord that are highly variable in terms of cellular content. Here, we used imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within staged MS lesions. To test the potential for IMC to ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.48051
更新日期:2019-08-01 00:00:00
abstract::Cytoplasmic dynein plays critical roles within the developing and mature nervous systems, including effecting nuclear migration, and retrograde transport of various cargos. Unsurprisingly, mutations in dynein are causative of various developmental neuropathies and motor neuron diseases. These 'dyneinopathies' define a...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47246
更新日期:2019-07-31 00:00:00
abstract::In many plant species, a subset of transcribed genes are characterized by strictly CG-context DNA methylation, referred to as gene body methylation (gbM). The mechanisms that establish gbM are unclear, yet flowering plant species naturally without gbM lack the DNA methyltransferase, CMT3, which maintains CHG (H = A, C...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47891
更新日期:2019-07-29 00:00:00
abstract::Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of Podospora anserina, seven spore killer types (Psks) have been identified through classical genetic analyses. Here we show that the S...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46454
更新日期:2019-07-26 00:00:00
abstract::Humans and other animals base important decisions on estimates of number, and intraparietal cortex is thought to provide a crucial substrate of this ability. However, it remains debated whether an independent neuronal processing mechanism underlies this 'number sense', or whether number is instead judged indirectly on...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45160
更新日期:2019-07-24 00:00:00
abstract::The light environment greatly impacts human alertness, mood, and cognition by both acute regulation of physiology and indirect alignment of circadian rhythms. These processes require the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), but the relevant downstream brain areas involved...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.44358
更新日期:2019-07-23 00:00:00
abstract::Glucocorticoid receptors (GR) have diverse functions relevant to maintenance of homeostasis and adaptation to environmental challenges. Understanding the importance of tissue-specific GR function in physiology and behavior has been hampered by near-ubiquitous localization in brain and body. Here we use CRISPR/Cas9 gen...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.44672
更新日期:2019-07-22 00:00:00
abstract::The fitness effects of synonymous mutations, nucleotide changes that do not alter the encoded amino acid, have often been assumed to be neutral, but a growing body of evidence suggests otherwise. We used site-directed mutagenesis coupled with direct measures of competitive fitness to estimate the distribution of fitne...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45952
更新日期:2019-07-19 00:00:00
abstract::TMEM16F is activated by elevated intracellular Ca2+, and functions as a small-conductance ion channel and as a phospholipid scramblase. In contrast to its paralogs, the TMEM16A/B calcium-activated chloride channels, mouse TMEM16F has been reported as a cation-, anion-, or non-selective ion channel, without a definite ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45187
更新日期:2019-07-18 00:00:00
abstract::Metabolic cycles are a fundamental element of cellular and organismal function. Among the most critical in higher organisms is the Cori Cycle, the systemic cycling between lactate and glucose. Here, skeletal muscle-specific Mitochondrial Pyruvate Carrier (MPC) deletion in mice diverted pyruvate into circulating lactat...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45873
更新日期:2019-07-18 00:00:00
abstract::We previously showed in Drosophila melanogaster embryos that low-affinity Ultrabithorax (Ubx)-responsive shavenbaby (svb) enhancers drive expression using localized transcriptional environments and that active svb enhancers on different chromosomes tended to colocalize (Tsai et al., 2017). Here, we test the hypothesis...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45325
更新日期:2019-07-11 00:00:00
abstract::Non-segmented negative-strand RNA viruses, such as measles, ebola and Newcastle disease viruses (NDV), encapsidate viral genomic RNAs into helical nucleocapsids, which serve as the template for viral replication and transcription. Here, the clam-shaped nucleocapsid structure, where the NDV viral genome is sequestered,...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45057
更新日期:2019-07-10 00:00:00
abstract::Iron storage proteins are essential for cellular iron homeostasis and redox balance. Ferritin proteins are the major storage units for bioavailable forms of iron. Some organisms lack ferritins, and it is not known how they store iron. Encapsulins, a class of protein-based organelles, have recently been implicated in m...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46070
更新日期:2019-07-08 00:00:00
abstract::Adult neurogenesis in the hippocampus may represent a form of plasticity in brain functions including mood, learning and memory. However, mechanisms underlying neural stem/progenitor cells (NSPCs) proliferation are not well understood. We found that Agrin, a factor critical for neuromuscular junction formation, is ele...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45303
更新日期:2019-07-03 00:00:00
abstract:: ...
journal_title:eLife
pub_type: 已发布勘误
doi:10.7554/eLife.49823
更新日期:2019-07-02 00:00:00
abstract::Dyneins are motor proteins responsible for transport in the cytoplasm and the beating of axonemes in cilia and flagella. They bind and release microtubules via a compact microtubule-binding domain (MTBD) at the end of a coiled-coil stalk. We address how cytoplasmic and axonemal dynein MTBDs bind microtubules at near a...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47145
更新日期:2019-07-02 00:00:00
abstract::Cancer cells usually exhibit aberrant cell signaling and metabolic reprogramming. However, mechanisms of crosstalk between these processes remain elusive. Here, we show that in an in vivo tumor model expressing oncogenic Drosophila Homeodomain-interacting protein kinase (Hipk), tumor cells display elevated aerobic gly...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46315
更新日期:2019-07-01 00:00:00
abstract::Although respiratory syncytial virus (RSV) is responsible for more human deaths each year than influenza, its pathogenic mechanisms are poorly understood. Here high-resolution quantitative imaging, bioenergetics measurements and mitochondrial membrane potential- and redox-sensitive dyes are used to define RSV's impact...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.42448
更新日期:2019-06-27 00:00:00
abstract::Some anaerobic bacteria use insoluble minerals as terminal electron acceptors and discovering the ways in which electrons move through the membrane barrier to the exterior acceptor forms an active field of research with implications for both bacterial physiology and bioenergy. A previous study suggested that Shewanell...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.48054
更新日期:2019-06-24 00:00:00
abstract::Many pathogens possess the capacity for sex through outcrossing, despite being able to reproduce also asexually and/or via selfing. Given that sex is assumed to come at a cost, these mixed reproductive strategies typical of pathogens have remained puzzling. While the ecological and evolutionary benefits of outcrossing...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47091
更新日期:2019-06-18 00:00:00