Genetically tunable frustration controls allostery in an intrinsically disordered transcription factor.

abstract：:Lissencephaly ('smooth brain') is a severe brain disease associated with numerous symptoms, including cognitive impairment, and shortened lifespan. The main causative gene of this disease - lissencephaly-1 (LIS1) - has been a focus of intense scrutiny since its first identification almost 30 years ago. LIS1 is a criti...

journal_title：eLife

authors： Markus SM,Marzo MG,McKenney RJ

更新日期：2020-07-21 00:00:00

abstract：:Methyl-coenzyme M reductase (MCR), found in strictly anaerobic methanogenic and methanotrophic archaea, catalyzes the reversible production and consumption of the potent greenhouse gas methane. The α subunit of MCR (McrA) contains several unusual post-translational modifications, including a rare thioamidation of glyc...

journal_title：eLife

authors： Nayak DD,Mahanta N,Mitchell DA,Metcalf WW

更新日期：2017-09-07 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

authors： Zhong G,He J,Zhou R,Lorenzo D,Babcock HP,Bennett V,Zhuang X

更新日期：2014-12-23 00:00:00

abstract：:Malaria infection starts with injection of Plasmodium sporozoites by an Anopheles mosquito into the skin of the mammalian host. How sporozoites locate and enter a blood vessel is a critical, but poorly understood process. In this study, we examine sporozoite motility and their interaction with dermal blood vessels, us...

journal_title：eLife

authors： Hopp CS,Chiou K,Ragheb DR,Salman AM,Khan SM,Liu AJ,Sinnis P

更新日期：2015-08-13 00:00:00

abstract：:Polypyrimidine-tract binding protein PTBP1 can repress splicing during the exon definition phase of spliceosome assembly, but the assembly steps leading to an exon definition complex (EDC) and how PTBP1 might modulate them are not clear. We found that PTBP1 binding in the flanking introns allowed normal U2AF and U1 sn...

journal_title：eLife

authors： Wongpalee SP,Vashisht A,Sharma S,Chui D,Wohlschlegel JA,Black DL

更新日期：2016-11-24 00:00:00

abstract：:How does attentional modulation of neural activity enhance performance? Here we use a deep convolutional neural network as a large-scale model of the visual system to address this question. We model the feature similarity gain model of attention, in which attentional modulation is applied according to neural stimulus ...

journal_title：eLife

authors： Lindsay GW,Miller KD

更新日期：2018-10-01 00:00:00

abstract：:Studies of the performance of individuals with dyslexia in perceptual tasks suggest that their implicit inference of sound statistics is impaired. Previously, using two-tone frequency discrimination, we found that the effect of previous trials' frequencies on the judgments of individuals with dyslexia decays faster th...

journal_title：eLife

authors： Jaffe-Dax S,Kimel E,Ahissar M

更新日期：2018-02-28 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：:Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and previous we have shown that these two effectors are also needed for mitochondrial-dependent cellular necrosis (Karch et al., 2013). Here we show that mouse embryonic fibroblasts deficient in Bax/Bak...

journal_title：eLife

authors： Karch J,Schips TG,Maliken BD,Brody MJ,Sargent MA,Kanisicak O,Molkentin JD

更新日期：2017-11-17 00:00:00

abstract：:Current models successfully describe the auditory cortical response to natural sounds with a set of spectro-temporal features. However, these models have hardly been linked to the ill-understood neurobiological changes that occur in the aging auditory cortex. Modelling the hemodynamic response to a rich natural sound ...

journal_title：eLife

authors： Erb J,Schmitt LM,Obleser J

更新日期：2020-07-03 00:00:00

abstract：:Skeletal muscle degeneration is a complication arising from a variety of chronic diseases including advanced cancer. Pro-inflammatory cytokine TNF-α plays a pivotal role in mediating cancer-related skeletal muscle degeneration. Here, we show a novel function for retinoblastoma protein (Rb), where Rb causes sarcomeric ...

journal_title：eLife

authors： Araki K,Kawauchi K,Hirata H,Yamamoto M,Taya Y

更新日期：2013-12-03 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：:Pore-blocking toxins inhibit voltage-dependent K(+) channels (Kv channels) by plugging the ion-conduction pathway. We have solved the crystal structure of paddle chimera, a Kv channel in complex with charybdotoxin (CTX), a pore-blocking toxin. The toxin binds to the extracellular pore entryway without producing discer...

journal_title：eLife

authors： Banerjee A,Lee A,Campbell E,Mackinnon R

更新日期：2013-05-21 00:00:00

abstract：:Down syndrome (DS) results in various degrees of cognitive deficits. In DS mouse models, recovery of behavioral and neurophysiological deficits using GABAAR antagonists led to hypothesize an excessive activity of inhibitory circuits in this condition. Nonetheless, whether over-inhibition is present in DS and whether t...

journal_title：eLife

authors： Zorrilla de San Martin J,Donato C,Peixoto J,Aguirre A,Choudhary V,De Stasi AM,Lourenço J,Potier MC,Bacci A

更新日期：2020-08-12 00:00:00

abstract：:Aging is characterized by extensive metabolic reprogramming. To identify metabolic pathways associated with aging, we analyzed age-dependent changes in the metabolomes of long-lived Drosophila melanogaster. Among the metabolites that changed, levels of tyrosine were increased with age in long-lived flies. We demonstra...

journal_title：eLife

authors： Parkhitko AA,Ramesh D,Wang L,Leshchiner D,Filine E,Binari R,Olsen AL,Asara JM,Cracan V,Rabinowitz JD,Brockmann A,Perrimon N

更新日期：2020-12-15 00:00:00

abstract：:Hair follicle (HF) development is orchestrated by coordinated signals from adjacent epithelial and mesenchymal cells. In humans this process only occurs during embryogenesis and viable strategies to induce new HFs in adult skin are lacking. Here, we reveal that activation of Hedgehog (Hh) signaling in adjacent epithel...

journal_title：eLife

authors： Sun X,Are A,Annusver K,Sivan U,Jacob T,Dalessandri T,Joost S,Füllgrabe A,Gerling M,Kasper M

更新日期：2020-03-17 00:00:00

abstract：:Peroxiredoxins are H2O2 scavenging enzymes that also carry out H2O2 signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H2O2 and extending lifespan upon caloric restriction. We show here that Tsa1 effects both these functions not by scavengi...

journal_title：eLife

authors： Roger F,Picazo C,Reiter W,Libiad M,Asami C,Hanzén S,Gao C,Lagniel G,Welkenhuysen N,Labarre J,Nyström T,Grøtli M,Hartl M,Toledano MB,Molin M

更新日期：2020-07-14 00:00:00

abstract：:The progenitor cells of the developing liver can differentiate toward both hepatocyte and biliary cell fates. In addition to the established roles of TGFβ and Notch signaling in this fate specification process, there is increasing evidence that liver progenitors are sensitive to mechanical cues. Here, we utilized micr...

journal_title：eLife

authors： Kaylan KB,Berg IC,Biehl MJ,Brougham-Cook A,Jain I,Jamil SM,Sargeant LH,Cornell NJ,Raetzman LT,Underhill GH

更新日期：2018-12-27 00:00:00

abstract：:The neural control of transition between posture and movement encompasses the regulation of reflex-stabilizing mechanisms to enable motion. Optimal feedback theory suggests that such transitions require the disengagement of one motor control policy before the implementation of another. To test this possibility, we inv...

journal_title：eLife

authors： Tisserand R,Dakin CJ,Van der Loos MH,Croft EA,Inglis TJ,Blouin JS

更新日期：2018-07-10 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：:Corticostriatal afferents can engage parvalbumin-expressing (PV+) interneurons to rapidly curtail the activity of striatal projection neurons (SPNs), thus shaping striatal output. Schemes of basal ganglia circuit dynamics generally consider striatal PV+ interneurons to be homogenous, despite considerable heterogeneity...

journal_title：eLife

authors： Garas FN,Shah RS,Kormann E,Doig NM,Vinciati F,Nakamura KC,Dorst MC,Smith Y,Magill PJ,Sharott A

更新日期：2016-09-26 00:00:00

abstract：:Transient receptor potential vanilloid 5 (TRPV5) is a highly calcium selective ion channel that acts as the rate-limiting step of calcium reabsorption in the kidney. The lack of potent, specific modulators of TRPV5 has limited the ability to probe the contribution of TRPV5 in disease phenotypes such as hypercalcemia a...

journal_title：eLife

authors： Hughes TE,Del Rosario JS,Kapoor A,Yazici AT,Yudin Y,Fluck EC 3rd,Filizola M,Rohacs T,Moiseenkova-Bell VY

更新日期：2019-10-25 00:00:00

abstract：:Examining whether and how the rhythms of limb and breathing movements interact is highly informative about the mechanistic origin of hyperpnoea during running exercise. However, studies have failed to reveal regularities. In particular, whether breathing frequency is inherently proportional to limb velocity and impose...

journal_title：eLife

authors： Hérent C,Diem S,Fortin G,Bouvier J

更新日期：2020-12-01 00:00:00

abstract：:Signal transduction at vertebrate excitatory synapses involves the rapid activation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptors, glutamate-gated ion channels whose four subunits assemble as a dimer-of-dimers. Technical advances in cryo-electron microscopy brought a slew of full-length structu...

journal_title：eLife

authors： Baranovic J,Plested AJ

更新日期：2018-12-06 00:00:00

abstract：:Gap junctions are widely distributed in the brains across species and play essential roles in neural information processing. However, the role of gap junctions in insect cognition remains poorly understood. Using a flight simulator paradigm and genetic tools, we found that gap junctions are present in Drosophila Kenyo...

journal_title：eLife

authors： Liu Q,Yang X,Tian J,Gao Z,Wang M,Li Y,Guo A

更新日期：2016-05-24 00:00:00

abstract：:While traditional microbiological freshwater tests focus on the detection of specific bacterial indicator species, including pathogens, direct tracing of all aquatic DNA through metagenomics poses a profound alternative. Yet, in situ metagenomic water surveys face substantial challenges in cost and logistics. Here, we...

journal_title：eLife

authors： Urban L,Holzer A,Baronas JJ,Hall MB,Braeuninger-Weimer P,Scherm MJ,Kunz DJ,Perera SN,Martin-Herranz DE,Tipper ET,Salter SJ,Stammnitz MR

更新日期：2021-01-19 00:00:00

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

authors： Olds WH,Xu T

更新日期：2014-10-06 00:00:00

abstract：:The basal ganglia are known to be involved in the planning, execution and control of gripping force and movement vigour. Here we aim to define the nature of the basal ganglia control signal for force and to decode gripping force based on local field potential (LFP) activities recorded from the subthalamic nucleus (STN...

journal_title：eLife

authors： Tan H,Pogosyan A,Ashkan K,Green AL,Aziz T,Foltynie T,Limousin P,Zrinzo L,Hariz M,Brown P

更新日期：2016-11-18 00:00:00

abstract：:Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours o...

journal_title：eLife

authors： Havekes R,Park AJ,Tudor JC,Luczak VG,Hansen RT,Ferri SL,Bruinenberg VM,Poplawski SG,Day JP,Aton SJ,Radwańska K,Meerlo P,Houslay MD,Baillie GS,Abel T

更新日期：2016-08-23 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

authors： Lim S

更新日期：2019-08-08 00:00:00