Deep learning models predict regulatory variants in pancreatic islets and refine type 2 diabetes association signals.

abstract：:Genomic rearrangements associated with speciation often result in variation in chromosome number among closely related species. Malassezia species show variable karyotypes ranging between six and nine chromosomes. Here, we experimentally identified all eight centromeres in M. sympodialis as 3-5-kb long kinetochore-bou...

journal_title：eLife

authors： Sankaranarayanan SR,Ianiri G,Coelho MA,Reza MH,Thimmappa BC,Ganguly P,Vadnala RN,Sun S,Siddharthan R,Tellgren-Roth C,Dawson TL Jnr,Heitman J,Sanyal K

更新日期：2020-01-20 00:00:00

abstract：:Cells use molecular circuits to interpret and respond to extracellular cues, such as hormones and cytokines, which are often released in a temporally varying fashion. In this study, we combine microfluidics, time-lapse microscopy, and computational modeling to investigate how the type I interferon (IFN)-responsive reg...

journal_title：eLife

authors： Mudla A,Jiang Y,Arimoto KI,Xu B,Rajesh A,Ryan AP,Wang W,Daugherty MD,Zhang DE,Hao N

更新日期：2020-09-18 00:00:00

abstract：:Metabolism of host-targeted drugs by the microbiome can substantially impact host treatment success. However, since many host-targeted drugs inadvertently hamper microbiome growth, repeated drug administration can lead to microbiome evolutionary adaptation. We tested if evolved bacterial resistance against host-target...

journal_title：eLife

authors： Rosener B,Sayin S,Oluoch PO,García González AP,Mori H,Walhout AJ,Mitchell A

更新日期：2020-11-30 00:00:00

abstract：:Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Ge...

journal_title：eLife

authors： Grosso AR,Leite AP,Carvalho S,Matos MR,Martins FB,Vítor AC,Desterro JM,Carmo-Fonseca M,de Almeida SF

更新日期：2015-11-17 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

authors： Sosa BA,Demircioglu FE,Chen JZ,Ingram J,Ploegh HL,Schwartz TU

更新日期：2014-08-22 00:00:00

abstract：:Establishing a link between the nonsense-mediated decay pathway and a gene associated with programmed cell death could explain why this pathway is essential in most, but not all, eukaryotes. ...

journal_title：eLife

authors： Saveanu C,Jacquier A

更新日期：2016-04-27 00:00:00

abstract：:The sense of ownership of one's body is important for survival, e.g., in defending the body against a threat. However, in addition to affecting behavior, it also affects perception of the world. In the case of visuospatial perception, it has been shown that the sense of ownership causes external space to be perceptual...

journal_title：eLife

authors： van der Hoort B,Reingardt M,Ehrsson HH

更新日期：2017-08-17 00:00:00

abstract：:A small molecule called Sm4 can disrupt interactions involving a transcription factor called Sox18, while having little impact on other members of the SoxF family. ...

journal_title：eLife

authors： Kim I,Koh GY

更新日期：2017-01-31 00:00:00

abstract：:Excitatory and inhibitory synapses are the brain's most abundant synapse types. However, little is known about their formation during critical periods of motor skill learning, when sensory experience defines a motor target that animals strive to imitate. In songbirds, we find that exposure to tutor song leads to elimi...

journal_title：eLife

authors： Huang Z,Khaled HG,Kirschmann M,Gobes SM,Hahnloser RH

更新日期：2018-10-25 00:00:00

abstract：:Mechanical force is a determinant of Notch signalling but the mechanism of force detection and its coupling to Notch are unclear. We propose a role for Piezo1 channels, which are mechanically-activated non-selective cation channels. In cultured microvascular endothelial cells, Piezo1 channel activation by either shear...

journal_title：eLife

authors： Caolo V,Debant M,Endesh N,Futers TS,Lichtenstein L,Bartoli F,Parsonage G,Jones EA,Beech DJ

更新日期：2020-06-02 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

authors： Wheaton WW,Weinberg SE,Hamanaka RB,Soberanes S,Sullivan LB,Anso E,Glasauer A,Dufour E,Mutlu GM,Budigner GS,Chandel NS

更新日期：2014-05-13 00:00:00

abstract：:Mouse GnT1IP-L, and membrane-bound GnT1IP-S (MGAT4D) expressed in cultured cells inhibit MGAT1, the N-acetylglucosaminyltransferase that initiates the synthesis of hybrid and complex N-glycans. However, it is not known where in the secretory pathway GnT1IP-L inhibits MGAT1, nor whether GnT1IP-L inhibits other N-glycan...

journal_title：eLife

authors： Huang HH,Hassinen A,Sundaram S,Spiess AN,Kellokumpu S,Stanley P

更新日期：2015-09-15 00:00:00

abstract：:The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during...

journal_title：eLife

authors： Crouse RB,Kim K,Batchelor HM,Girardi EM,Kamaletdinova R,Chan J,Rajebhosale P,Pittenger ST,Role LW,Talmage DA,Jing M,Li Y,Gao XB,Mineur YS,Picciotto MR

更新日期：2020-09-18 00:00:00

abstract：:Although several sleep-regulating neuronal populations have been identified, little is known about how they interact with each other to control sleep/wake states. We previously identified neuropeptide VF (NPVF) and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al., 2017). Here we show us...

journal_title：eLife

authors： Lee DA,Oikonomou G,Cammidge T,Andreev A,Hong Y,Hurley H,Prober DA

更新日期：2020-12-18 00:00:00

abstract：:The twin-arginine protein translocation system (Tat) transports folded proteins across the bacterial cytoplasmic membrane and the thylakoid membranes of plant chloroplasts. The Tat transporter is assembled from multiple copies of the membrane proteins TatA, TatB, and TatC. We combine sequence co-evolution analysis, mo...

journal_title：eLife

authors： Alcock F,Stansfeld PJ,Basit H,Habersetzer J,Baker MA,Palmer T,Wallace MI,Berks BC

更新日期：2016-12-03 00:00:00

abstract：:When an individual makes a judgement about the actions of another individual, taking the latter's viewpoint into consideration enhances cooperation in society at large. ...

journal_title：eLife

authors： Masuda N,Santos FC

更新日期：2019-04-29 00:00:00

abstract：:The insular cortex (IC) plays key roles in emotional and regulatory brain functions and is affected across psychiatric diseases. However, the brain-wide connections of the mouse IC have not been comprehensively mapped. Here, we traced the whole-brain inputs and outputs of the mouse IC across its rostro-caudal extent. ...

journal_title：eLife

authors： Gehrlach DA,Weiand C,Gaitanos TN,Cho E,Klein AS,Hennrich AA,Conzelmann KK,Gogolla N

更新日期：2020-09-17 00:00:00

abstract：:Canonical transient receptor potential channels (TRPC) are involved in receptor-operated and/or store-operated Ca2+ signaling. Inhibition of TRPCs by small molecules was shown to be promising in treating renal diseases. In cells, the channels are regulated by calmodulin (CaM). Molecular details of both CaM and drug bi...

journal_title：eLife

authors： Vinayagam D,Quentin D,Yu-Strzelczyk J,Sitsel O,Merino F,Stabrin M,Hofnagel O,Yu M,Ledeboer MW,Nagel G,Malojcic G,Raunser S

更新日期：2020-11-25 00:00:00

abstract：:We discovered that Enterococcus faecium (E. faecium), a ubiquitous commensal bacterium, and its secreted peptidoglycan hydrolase (SagA) were sufficient to enhance intestinal barrier function and pathogen tolerance, but the precise biochemical mechanism was unknown. Here we show E. faecium has unique peptidoglycan comp...

journal_title：eLife

authors： Kim B,Wang YC,Hespen CW,Espinosa J,Salje J,Rangan KJ,Oren DA,Kang JY,Pedicord VA,Hang HC

更新日期：2019-04-10 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

authors： Mordecai GJ,Miller KM,Di Cicco E,Schulze AD,Kaukinen KH,Ming TJ,Li S,Tabata A,Teffer A,Patterson DA,Ferguson HW,Suttle CA

更新日期：2019-09-03 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

authors： Davidsen K,Olson BJ,DeWitt WS 3rd,Feng J,Harkins E,Bradley P,Matsen FA 4th

更新日期：2019-09-05 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

authors： Wisniewska DM,Ratcliffe JM,Beedholm K,Christensen CB,Johnson M,Koblitz JC,Wahlberg M,Madsen PT

更新日期：2015-03-20 00:00:00

abstract：:Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to stu...

journal_title：eLife

authors： Matias S,Lottem E,Dugué GP,Mainen ZF

更新日期：2017-03-21 00:00:00

abstract：:As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Blum et al., 2015), that described how we intended to replicate selected experiments from the paper 'Transcriptional amplification in tumor cells with elevated c-Myc' (Lin et al., 2012). Here we report the results. We found overe...

journal_title：eLife

authors： Lewis LM,Edwards MC,Meyers ZR,Talbot CC Jr,Hao H,Blum D,Reproducibility Project: Cancer Biology.

更新日期：2018-01-09 00:00:00

abstract：:Cell-type-specific 3D organization of the genome is unrecognizable during mitosis. It remains unclear how essential positional information is transmitted through cell division such that a daughter cell recapitulates the spatial genome organization of the parent. Lamina-associated domains (LADs) are regions of repressi...

journal_title：eLife

authors： Poleshko A,Smith CL,Nguyen SC,Sivaramakrishnan P,Wong KG,Murray JI,Lakadamyali M,Joyce EF,Jain R,Epstein JA

更新日期：2019-10-01 00:00:00

abstract：:Pioneer factors such as Zelda (Zld) help initiate zygotic transcription in Drosophila early embryos, but whether other factors support this dynamic process is unclear. Odd-paired (Opa), a zinc-finger transcription factor expressed at cellularization, controls the transition of genes from pair-rule to segmental pattern...

journal_title：eLife

authors： Koromila T,Gao F,Iwasaki Y,He P,Pachter L,Gergen JP,Stathopoulos A

更新日期：2020-07-23 00:00:00

abstract：:The numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by important known stem cell-extrinsic signals. However, the cell-intrinsic mechanisms that control the distinctive proliferation rates of individual neural stem cells ar...

journal_title：eLife

authors： Samuels TJ,Järvelin AI,Ish-Horowicz D,Davis I

更新日期：2020-01-14 00:00:00

abstract：:Obesity produces a chronic inflammatory state involving the NFκB pathway, resulting in persistent elevation of the noncanonical IκB kinases IKKε and TBK1. In this study, we report that these kinases attenuate β-adrenergic signaling in white adipose tissue. Treatment of 3T3-L1 adipocytes with specific inhibitors of the...

journal_title：eLife

authors： Mowers J,Uhm M,Reilly SM,Simon J,Leto D,Chiang SH,Chang L,Saltiel AR

更新日期：2013-12-24 00:00:00

abstract：:DNA is a remarkably precise medium for copying and storing biological information. This high fidelity results from the action of hundreds of genes involved in replication, proofreading, and damage repair. Evolutionary theory suggests that in such a system, selection has limited ability to remove genetic variants that ...

journal_title：eLife

authors： Harris K,Pritchard JK

更新日期：2017-04-25 00:00:00

abstract：:A small transparent crustacean called Parhyale hawaiensis has become a powerful model system for the study of limb and appendage regeneration. ...

journal_title：eLife

authors： Amaya E

更新日期：2016-10-25 00:00:00