Chemical structure-guided design of dynapyrazoles, cell-permeable dynein inhibitors with a unique mode of action.

abstract：: ...

journal_title：eLife

authors： Hayasaka N,Hirano A,Miyoshi Y,Tokuda IT,Yoshitane H,Matsuda J,Fukada Y

更新日期：2021-01-25 00:00:00

abstract：:During land plant evolution, determinate spore-bearing axes (retained in extant bryophytes such as mosses) were progressively transformed into indeterminate branching shoots with specialized reproductive axes that form flowers. The LEAFY transcription factor, which is required for the first zygotic cell division in mo...

journal_title：eLife

authors： Plackett AR,Conway SJ,Hewett Hazelton KD,Rabbinowitsch EH,Langdale JA,Di Stilio VS

更新日期：2018-10-24 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

authors： Palmieri N,Kosiol C,Schlötterer C

更新日期：2014-02-19 00:00:00

abstract：:Animals exhibit innate behaviours to a variety of sensory stimuli including olfactory cues. In Drosophila, one higher olfactory centre, the lateral horn (LH), is implicated in innate behaviour. However, our structural and functional understanding of the LH is scant, in large part due to a lack of sparse neurogenetic t...

journal_title：eLife

authors： Dolan MJ,Frechter S,Bates AS,Dan C,Huoviala P,Roberts RJ,Schlegel P,Dhawan S,Tabano R,Dionne H,Christoforou C,Close K,Sutcliffe B,Giuliani B,Li F,Costa M,Ihrke G,Meissner GW,Bock DD,Aso Y,Rubin GM,Jefferis GS

更新日期：2019-05-21 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：:Newly born cells either continue to proliferate or exit the cell division cycle. This decision involves delaying expression of Cyclin E that promotes DNA replication. ORC1, the Origin Recognition Complex (ORC) large subunit, is inherited into newly born cells after it binds to condensing chromosomes during the precedi...

journal_title：eLife

authors： Hossain M,Stillman B

更新日期：2016-07-26 00:00:00

abstract：:Damaged mitochondria are selectively eliminated by mitophagy. Parkin and PINK1, gene products mutated in familial Parkinson's disease, play essential roles in mitophagy through ubiquitination of mitochondria. Cargo ubiquitination by E3 ubiquitin ligase Parkin is important to trigger selective autophagy. Although autop...

journal_title：eLife

authors： Yamano K,Wang C,Sarraf SA,Münch C,Kikuchi R,Noda NN,Hizukuri Y,Kanemaki MT,Harper W,Tanaka K,Matsuda N,Youle RJ

更新日期：2018-01-23 00:00:00

abstract：:Transport of biologically active molecules across tight epithelial barriers is a major challenge preventing therapeutic peptides from oral drug delivery. Here, we identify a set of synthetic glycosphingolipids that harness the endogenous process of intracellular lipid-sorting to enable mucosal absorption of the incret...

journal_title：eLife

authors： Garcia-Castillo MD,Chinnapen DJ,Te Welscher YM,Gonzalez RJ,Softic S,Pacheco M,Mrsny RJ,Kahn CR,von Andrian UH,Lau J,Pentelute BL,Lencer WI

更新日期：2018-05-31 00:00:00

abstract：:Ki-67 and RepoMan have key roles during mitotic exit. Previously, we showed that Ki-67 organizes the mitotic chromosome periphery and recruits protein phosphatase 1 (PP1) to chromatin at anaphase onset, in a similar manner as RepoMan (Booth et al., 2014). Here we show how Ki-67 and RepoMan form mitotic exit phosphatas...

journal_title：eLife

authors： Kumar GS,Gokhan E,De Munter S,Bollen M,Vagnarelli P,Peti W,Page R

更新日期：2016-08-30 00:00:00

abstract：:hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Usin...

journal_title：eLife

authors： Krotee P,Rodriguez JA,Sawaya MR,Cascio D,Reyes FE,Shi D,Hattne J,Nannenga BL,Oskarsson ME,Philipp S,Griner S,Jiang L,Glabe CG,Westermark GT,Gonen T,Eisenberg DS

更新日期：2017-01-03 00:00:00

abstract：:When a female fly mates it produces a hormone that increases the size of its midgut and enhances fat metabolism in order to provide the energy needed for reproduction. ...

journal_title：eLife

authors： Flatt T

更新日期：2015-07-28 00:00:00

abstract：:The asymmetric outer membrane (OM) of Gram-negative bacteria functions as a selective permeability barrier to the environment. Perturbations to OM lipid asymmetry sensitize the cell to antibiotics. As such, mechanisms involved in lipid asymmetry are fundamental to our understanding of OM lipid homeostasis. One such me...

journal_title：eLife

authors： Powers MJ,Simpson BW,Trent MS

更新日期：2020-09-03 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

authors： Hosmillo M,Lu J,McAllaster MR,Eaglesham JB,Wang X,Emmott E,Domingues P,Chaudhry Y,Fitzmaurice TJ,Tung MK,Panas MD,McInerney G,Locker N,Wilen CB,Goodfellow IG

更新日期：2019-08-12 00:00:00

abstract：:An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here, we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible...

journal_title：eLife

authors： Jänes J,Dong Y,Schoof M,Serizay J,Appert A,Cerrato C,Woodbury C,Chen R,Gemma C,Huang N,Kissiov D,Stempor P,Steward A,Zeiser E,Sauer S,Ahringer J

更新日期：2018-10-26 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：:Actin filaments assemble inside the nucleus in response to multiple cellular perturbations, including heat shock, protein misfolding, integrin engagement, and serum stimulation. We find that DNA damage also generates nuclear actin filaments-detectable by phalloidin and live-cell actin probes-with three characteristic ...

journal_title：eLife

authors： Belin BJ,Lee T,Mullins RD

更新日期：2015-08-19 00:00:00

abstract：:The voltage-gated K+ channel Kv2.1 serves a major structural role in the soma and proximal dendrites of mammalian brain neurons, tethering the plasma membrane (PM) to endoplasmic reticulum (ER). Although Kv2.1 clustering at neuronal ER-PM junctions (EPJs) is tightly regulated and highly conserved, its function remains...

journal_title：eLife

authors： Vierra NC,Kirmiz M,van der List D,Santana LF,Trimmer JS

更新日期：2019-10-30 00:00:00

abstract：:Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perfori...

journal_title：eLife

authors： McCormack RM,de Armas LR,Shiratsuchi M,Fiorentino DG,Olsson ML,Lichtenheld MG,Morales A,Lyapichev K,Gonzalez LE,Strbo N,Sukumar N,Stojadinovic O,Plano GV,Munson GP,Tomic-Canic M,Kirsner RS,Russell DG,Podack ER

更新日期：2015-09-24 00:00:00

abstract：:The >800 human G protein-coupled receptors (GPCRs) are responsible for transducing diverse chemical stimuli to alter cell state- and are the largest class of drug targets. Their myriad structural conformations and various modes of signaling make it challenging to understand their structure and function. Here, we devel...

journal_title：eLife

authors： Jones EM,Lubock NB,Venkatakrishnan AJ,Wang J,Tseng AM,Paggi JM,Latorraca NR,Cancilla D,Satyadi M,Davis JE,Babu MM,Dror RO,Kosuri S

更新日期：2020-10-21 00:00:00

abstract：:Oligomeric assemblies of intraflagellar transport (IFT) particles build cilia through sequential recruitment and transport of ciliary cargo proteins within cilia. Here we present the 1.8 Å resolution crystal structure of the Chlamydomonas IFT-B protein IFT80, which reveals the architecture of two N-terminal β-propelle...

journal_title：eLife

authors： Taschner M,Lorentzen A,Mourão A,Collins T,Freke GM,Moulding D,Basquin J,Jenkins D,Lorentzen E

更新日期：2018-04-16 00:00:00

abstract：:Bioluminescence is a powerful biological signal that scientists have repurposed as a reporter for gene expression in plants and animals. However, there are downsides associated with the need to provide a substrate to these reporters, including its high cost and non-uniform tissue penetration. In this work we reconstit...

journal_title：eLife

authors： Khakhar A,Starker CG,Chamness JC,Lee N,Stokke S,Wang C,Swanson R,Rizvi F,Imaizumi T,Voytas DF

更新日期：2020-03-25 00:00:00

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：:Studies of cell fate focus on specification, but little is known about maintenance of the differentiated state. In this study, we find that the mouse tendon cell fate requires continuous maintenance in vivo and identify an essential role for TGFβ signaling in maintenance of the tendon cell fate. To examine the role of...

journal_title：eLife

authors： Tan GK,Pryce BA,Stabio A,Brigande JV,Wang C,Xia Z,Tufa SF,Keene DR,Schweitzer R

更新日期：2020-01-21 00:00:00

abstract：:The interferon-inducible transmembrane (IFITM) proteins belong to the Dispanin/CD225 family and inhibit diverse virus infections. IFITM3 reduces membrane fusion between cells and virions through a poorly characterized mechanism. Mutation of proline-rich transmembrane protein 2 (PRRT2), a regulator of neurotransmitter ...

journal_title：eLife

authors： Rahman K,Coomer CA,Majdoul S,Ding SY,Padilla-Parra S,Compton AA

更新日期：2020-10-28 00:00:00

abstract：:The new open-access journal eLife has launched, making its first content available in PubMed Central. In addition to publishing science of the highest quality, the journal aims to improve both the peer-review process and the presentation of new research results. ...

journal_title：eLife

authors： Schekman R,Patterson M,Watt F,Weigel D

更新日期：2012-10-15 00:00:00

abstract：:Huntington disease (HD) is a neurological disorder caused by polyglutamine expansions in mutated Huntingtin (mHtt) proteins, rendering them prone to form inclusion bodies (IB). We report that in yeast, such IB formation is a factor-dependent process subjected to age-related decline. A genome-wide, high-content imaging...

journal_title：eLife

authors： Yang J,Hao X,Cao X,Liu B,Nyström T

更新日期：2016-04-01 00:00:00

abstract：:Advances in DNA sequencing have revolutionized our ability to read genomes. However, even in the most well-studied of organisms, the bacterium Escherichia coli, for ≈65% of promoters we remain ignorant of their regulation. Until we crack this regulatory Rosetta Stone, efforts to read and write genomes will remain haph...

journal_title：eLife

authors： Ireland WT,Beeler SM,Flores-Bautista E,McCarty NS,Röschinger T,Belliveau NM,Sweredoski MJ,Moradian A,Kinney JB,Phillips R

更新日期：2020-09-21 00:00:00

abstract：:Nuclear speckles (NS) are among the most prominent biomolecular condensates. Despite their prevalence, research on the function of NS is virtually restricted to colocalization analyses, since an organizing core, without which NS cannot form, remains unidentified. The monoclonal antibody SC35, raised against a spliceos...

journal_title：eLife

authors： Ilik İA,Malszycki M,Lübke AK,Schade C,Meierhofer D,Aktaş T

更新日期：2020-10-23 00:00:00

abstract：:Pattern completion, or the ability to retrieve stable neural activity patterns from noisy or partial cues, is a fundamental feature of memory. Theoretical studies indicate that recurrently connected auto-associative or discrete attractor networks can perform this process. Although pattern completion and attractor dyna...

journal_title：eLife

authors： Bolding KA,Nagappan S,Han BX,Wang F,Franks KM

更新日期：2020-07-14 00:00:00

abstract：:Ribosomes are universally important in biology and their production is dysregulated by developmental disorders, cancer, and virus infection. Although presumed required for protein synthesis, how ribosome biogenesis impacts virus reproduction and cell-intrinsic immune responses remains untested. Surprisingly, we find t...

journal_title：eLife

authors： Bianco C,Mohr I

更新日期：2019-12-16 00:00:00