Adaptation in protein fitness landscapes is facilitated by indirect paths.

abstract：:Anxiety results in sub-optimal motor learning, but the precise mechanisms through which this effect occurs remain unknown. Using a motor sequence learning paradigm with separate phases for initial exploration and reward-based learning, we show that anxiety states in humans impair learning by attenuating the update of ...

journal_title：eLife

authors： Sporn S,Hein T,Herrojo Ruiz M

更新日期：2020-05-19 00:00:00

abstract：:Meiotic crossovers result from homology-directed repair of DNA double-strand breaks (DSBs). Unlike yeast and plants, where DSBs are generated near gene promoters, in many vertebrates DSBs are enriched at hotspots determined by the DNA binding activity of the rapidly evolving zinc finger array of PRDM9 (PR domain zinc ...

journal_title：eLife

authors： Mahgoub M,Paiano J,Bruno M,Wu W,Pathuri S,Zhang X,Ralls S,Cheng X,Nussenzweig A,Macfarlan TS

更新日期：2020-04-30 00:00:00

abstract：:Antiviral development is plagued by drug resistance and genetic barriers to resistance are needed. For HIV and hepatitis C virus (HCV), combination therapy has proved life-saving. The targets of direct-acting antivirals for HCV infection are NS3/4A protease, NS5A phosphoprotein and NS5B polymerase. Differential visual...

journal_title：eLife

authors： van Buuren N,Tellinghuisen TL,Richardson CD,Kirkegaard K

更新日期：2018-03-28 00:00:00

abstract：:The time it takes a sound to travel from source to ear differs between the ears and creates an interaural delay. It varies systematically with spatial direction and is generally modeled as a pure time delay, independent of frequency. In acoustical recordings, we found that interaural delay varies with frequency at a f...

journal_title：eLife

authors： Benichoux V,Fontaine B,Franken TP,Karino S,Joris PX,Brette R

更新日期：2015-04-27 00:00:00

abstract：:Humans are motivated to seek information from their environment. How the brain motivates this behavior is unknown. One speculation is that the brain employs neuromodulatory systems implicated in primary reward-seeking, in particular dopamine, to instruct information-seeking. However, there has been no causal test for ...

journal_title：eLife

authors： Vellani V,de Vries LP,Gaule A,Sharot T

更新日期：2020-12-02 00:00:00

abstract：:In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational ch...

journal_title：eLife

authors： Cheng TC,Hong C,Akey IV,Yuan S,Akey CW

更新日期：2016-10-04 00:00:00

abstract：:The multi-domain splicing factor RBM5 regulates the balance between antagonistic isoforms of the apoptosis-control genes FAS/CD95, Caspase-2 and AID. An OCRE (OCtamer REpeat of aromatic residues) domain found in RBM5 is important for alternative splicing regulation and mediates interactions with components of the U4/U...

journal_title：eLife

authors： Mourão A,Bonnal S,Soni K,Warner L,Bordonné R,Valcárcel J,Sattler M

更新日期：2016-11-29 00:00:00

abstract：:Two gene variants provide different levels of protection against sleeping sickness, but this comes with an increased risk of developing chronic kidney disease. ...

journal_title：eLife

authors： Kruzel-Davila E,Skorecki K

更新日期：2017-07-03 00:00:00

abstract：:Rodents are emerging as increasingly popular models of visual functions. Yet, evidence that rodent visual cortex is capable of advanced visual processing, such as object recognition, is limited. Here we investigate how neurons located along the progression of extrastriate areas that, in the rat brain, run laterally to...

journal_title：eLife

authors： Tafazoli S,Safaai H,De Franceschi G,Rosselli FB,Vanzella W,Riggi M,Buffolo F,Panzeri S,Zoccolan D

更新日期：2017-04-11 00:00:00

abstract：:The incubation period for typhoid, polio, measles, leukemia and many other diseases follows a right-skewed, approximately lognormal distribution. Although this pattern was discovered more than sixty years ago, it remains an open question to explain its ubiquity. Here, we propose an explanation based on evolutionary dy...

journal_title：eLife

authors： Ottino-Loffler B,Scott JG,Strogatz SH

更新日期：2017-12-21 00:00:00

abstract：:Bacillus subtilis can measure the activity of the enzymes that remodel the cell wall to ensure that the levels of activity are 'just right'. ...

journal_title：eLife

authors： Kim IM,Szurmant H

更新日期：2020-01-24 00:00:00

abstract：:Nervous systems distinguish between self- and other-generated movements by monitoring discrepancies between planned and performed actions. To do so, corollary discharges are conveyed to sensory areas and gate expected reafference. Such gating is observed in neonatal rats during wake-related movements. In contrast, twi...

journal_title：eLife

authors： Tiriac A,Blumberg MS

更新日期：2016-08-03 00:00:00

abstract：:In most vertebrate neurons, action potentials are triggered at the distal end of the axon initial segment (AIS). Both position and length of the AIS vary across and within neuron types, with activity, development and pathology. What is the impact of AIS geometry on excitability? Direct empirical assessment has proven ...

journal_title：eLife

authors： Goethals S,Brette R

更新日期：2020-03-30 00:00:00

abstract：:The number of de novo mutations (DNMs) found in an offspring's genome increases with both paternal and maternal age. But does the rate of mutation accumulation in human gametes differ across families? Using sequencing data from 33 large, three-generation CEPH families, we observed significant variability in parental a...

journal_title：eLife

authors： Sasani TA,Pedersen BS,Gao Z,Baird L,Przeworski M,Jorde LB,Quinlan AR

更新日期：2019-09-24 00:00:00

abstract：:Entry and extrusion of cations are essential processes in living cells. In alkaliphilic prokaryotes, high external pH activates voltage-gated sodium channels (Nav), which allows Na(+) to enter and be used as substrate for cation/proton antiporters responsible for cytoplasmic pH homeostasis. Here, we describe a new mem...

journal_title：eLife

authors： DeCaen PG,Takahashi Y,Krulwich TA,Ito M,Clapham DE

更新日期：2014-11-11 00:00:00

abstract：:Coronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks SV capillary sprou...

journal_title：eLife

authors： Travisano SI,Oliveira VL,Prados B,Grego-Bessa J,Piñeiro-Sabarís R,Bou V,Gómez MJ,Sánchez-Cabo F,MacGrogan D,de la Pompa JL

更新日期：2019-12-04 00:00:00

abstract：:The factors that govern assembly of the gut microbiota are insufficiently understood. Here, we test the hypothesis that inter-individual microbiota variation can arise solely from differences in the order and timing by which the gut is colonized early in life. Experiments in which mice were inoculated in sequence eith...

journal_title：eLife

authors： Martínez I,Maldonado-Gomez MX,Gomes-Neto JC,Kittana H,Ding H,Schmaltz R,Joglekar P,Cardona RJ,Marsteller NL,Kembel SW,Benson AK,Peterson DA,Ramer-Tait AE,Walter J

更新日期：2018-09-18 00:00:00

abstract：:We tested the proposal that the C-terminal domain (CTD) of the AMPAR subunit GluA1 is required for LTP. We found that a knock-in mouse lacking the CTD of GluA1 expresses normal LTP and spatial memory, assayed by the Morris water maze. Our results support a model in which LTP generates synaptic slots, which capture pas...

journal_title：eLife

authors： Díaz-Alonso J,Morishita W,Incontro S,Simms J,Holtzman J,Gill M,Mucke L,Malenka RC,Nicoll RA

更新日期：2020-08-24 00:00:00

abstract：:Ageing is a progressive decline of intrinsic physiological functions. We examined the impact of ageing on the ultrastructure and function of mitochondria in mouse and fruit flies (Drosophila melanogaster) by electron cryo-tomography and respirometry. We discovered distinct age-related changes in both model organisms. ...

journal_title：eLife

authors： Brandt T,Mourier A,Tain LS,Partridge L,Larsson NG,Kühlbrandt W

更新日期：2017-07-12 00:00:00

abstract：:Breast cancer stem cells (BCSCs) contribute to intra-tumoral heterogeneity and therapeutic resistance. However, the binary concept of universal BCSCs co-existing with bulk tumor cells is over-simplified. Through single-cell RNA-sequencing, we found that Neu, PyMT and BRCA1-null mammary tumors each corresponded to a sp...

journal_title：eLife

authors： Yeo SK,Zhu X,Okamoto T,Hao M,Wang C,Lu P,Lu LJ,Guan JL

更新日期：2020-08-25 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：: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：:The two centrioles of the centrosome in quiescent cells are inherently asymmetric structures that differ in age, morphology and function. How these asymmetric properties are established and maintained during quiescence remains unknown. Here, we show that a daughter centriole-associated ciliopathy protein, Cep120, play...

journal_title：eLife

authors： Betleja E,Nanjundappa R,Cheng T,Mahjoub MR

更新日期：2018-05-09 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：:The straight-tusked elephants Palaeoloxodon spp. were widespread across Eurasia during the Pleistocene. Phylogenetic reconstructions using morphological traits have grouped them with Asian elephants (Elephas maximus), and many paleontologists place Palaeoloxodon within Elephas. Here, we report the recovery of full mit...

journal_title：eLife

authors： Meyer M,Palkopoulou E,Baleka S,Stiller M,Penkman KEH,Alt KW,Ishida Y,Mania D,Mallick S,Meijer T,Meller H,Nagel S,Nickel B,Ostritz S,Rohland N,Schauer K,Schüler T,Roca AL,Reich D,Shapiro B,Hofreiter M

更新日期：2017-06-06 00:00:00

abstract：:Microtubules are nucleated from specific locations at precise times in the cell cycle. However, the factors that constitute these microtubule nucleation pathways and their mode of action still need to be identified. Using purified Xenopus laevis proteins we biochemically reconstitute branching microtubule nucleation, ...

journal_title：eLife

authors： Alfaro-Aco R,Thawani A,Petry S

更新日期：2020-01-14 00:00:00

abstract：:Most neurogenesis in the mammalian brain is completed embryonically, but in certain areas the production of neurons continues throughout postnatal life. The functional properties of mature postnatally generated neurons often match those of their embryonically produced counterparts. However, we show here that in the ol...

journal_title：eLife

authors： Galliano E,Franzoni E,Breton M,Chand AN,Byrne DJ,Murthy VN,Grubb MS

更新日期：2018-04-20 00:00:00

abstract：:Anterograde transport of late endosomes or lysosomes (LE/Lys) is crucial for proper axon growth. However, the role of energetic nutrients has been poorly explored. Malonyl-CoA is a precursor of fatty acids, and its intracellular levels highly fluctuate depending on glucose availability or the energy sensor AMP-activat...

journal_title：eLife

authors： Palomo-Guerrero M,Fadó R,Casas M,Pérez-Montero M,Baena M,Helmer PO,Domínguez JL,Roig A,Serra D,Hayen H,Stenmark H,Raiborg C,Casals N

更新日期：2019-12-23 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：:TFIID-a complex of TATA-binding protein (TBP) and TBP-associated factors (TAFs)-is a central component of the Pol II promoter recognition apparatus. Recent studies have revealed significant downregulation of TFIID subunits in terminally differentiated myocytes, hepatocytes and adipocytes. Here, we report that TBP prot...

journal_title：eLife

authors： Li L,Martinez SS,Hu W,Liu Z,Tjian R

更新日期：2015-09-22 00:00:00