abstract：:The membrane-bound transcription factor ATF6α plays a cytoprotective role in the unfolded protein response (UPR), required for cells to survive ER stress. Activation of ATF6α promotes cell survival in cancer models. We used cell-based screens to discover and develop Ceapins, a class of pyrazole amides, that block ATF6...

journal_title：eLife

authors： Gallagher CM,Garri C,Cain EL,Ang KK,Wilson CG,Chen S,Hearn BR,Jaishankar P,Aranda-Diaz A,Arkin MR,Renslo AR,Walter P

更新日期：2016-07-20 00:00:00

abstract：:We recently reported that the C2AB portion of Synaptotagmin 1 (Syt1) could self-assemble into Ca(2+)-sensitive ring-like oligomers on membranes, which could potentially regulate neurotransmitter release. Here we report that analogous ring-like oligomers assemble from the C2AB domains of other Syt isoforms (Syt2, Syt7,...

journal_title：eLife

authors： Zanetti MN,Bello OD,Wang J,Coleman J,Cai Y,Sindelar CV,Rothman JE,Krishnakumar SS

更新日期：2016-07-19 00:00:00

abstract：:Experiments in which monkeys have to select or estimate the location of a target are revealing more about the role of the dorsal premotor cortex in decision making. ...

journal_title：eLife

authors： Stuphorn V

更新日期：2016-07-15 00:00:00

abstract：:We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were foun...

journal_title：eLife

authors： Wang Y,Sundfeldt K,Mateoiu C,Shih IeM,Kurman RJ,Schaefer J,Silliman N,Kinde I,Springer S,Foote M,Kristjansdottir B,James N,Kinzler KW,Papadopoulos N,Diaz LA,Vogelstein B

更新日期：2016-07-15 00:00:00

abstract：:Genetic programming and neural activity drive synaptic remodeling in developing neural circuits, but the molecular components that link these pathways are poorly understood. Here we show that the C. elegans Degenerin/Epithelial Sodium Channel (DEG/ENaC) protein, UNC-8, is transcriptionally controlled to function as a ...

journal_title：eLife

authors： Miller-Fleming TW,Petersen SC,Manning L,Matthewman C,Gornet M,Beers A,Hori S,Mitani S,Bianchi L,Richmond J,Miller DM

更新日期：2016-07-12 00:00:00

abstract：:The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two am...

journal_title：eLife

authors： Wu NC,Dai L,Olson CA,Lloyd-Smith JO,Sun R

更新日期：2016-07-08 00:00:00

abstract：:Increasing evidence highlights the important roles of microRNAs in mediating p53's tumor suppression functions. Here, we report miR-139-5p as another new p53 microRNA target. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an oncogenic protein i...

journal_title：eLife

authors： Cao B,Wang K,Liao JM,Zhou X,Liao P,Zeng SX,He M,Chen L,He Y,Li W,Lu H

更新日期：2016-07-07 00:00:00

abstract：:Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditi...

journal_title：eLife

authors： Watson E,Olin-Sandoval V,Hoy MJ,Li CH,Louisse T,Yao V,Mori A,Holdorf AD,Troyanskaya OG,Ralser M,Walhout AJ

更新日期：2016-07-06 00:00:00

abstract：:Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription fa...

journal_title：eLife

authors： Pérez Millán MI,Brinkmeier ML,Mortensen AH,Camper SA

更新日期：2016-06-28 00:00:00

abstract：:Vesicle fusion is mediated by an assembly of SNARE proteins between opposing membranes, but it is unknown whether transmembrane domains (TMDs) of SNARE proteins serve mechanistic functions that go beyond passive anchoring of the force-generating SNAREpin to the fusing membranes. Here, we show that conformational flexi...

journal_title：eLife

authors： Dhara M,Yarzagaray A,Makke M,Schindeldecker B,Schwarz Y,Shaaban A,Sharma S,Böckmann RA,Lindau M,Mohrmann R,Bruns D

更新日期：2016-06-25 00:00:00

abstract：:Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the ...

journal_title：eLife

authors： Li T,Giagtzoglou N,Eberl DF,Jaiswal SN,Cai T,Godt D,Groves AK,Bellen HJ

更新日期：2016-06-22 00:00:00

abstract：:Goal-directed behavior involves distributed neuronal circuits in the mammalian brain, including diverse regions of neocortex. However, the cellular basis of long-range cortico-cortical signaling during goal-directed behavior is poorly understood. Here, we recorded membrane potential of excitatory layer 2/3 pyramidal n...

journal_title：eLife

authors： Yamashita T,Petersen CCh

更新日期：2016-06-21 00:00:00

abstract：:Recent work draws attention to community-community encounters ('coalescence') as likely an important factor shaping natural ecosystems. This work builds on MacArthur's classic model of competitive coexistence to investigate such community-level competition in a minimal theoretical setting. It is shown that the ability...

journal_title：eLife

authors： Tikhonov M

更新日期：2016-06-16 00:00:00

abstract：:Neurons coding for head-direction are crucial for spatial navigation. Here we explored the cellular basis of head-direction coding in the rat dorsal presubiculum (PreS). We found that layer2 is composed of two principal cell populations (calbindin-positive and calbindin-negative neurons) which targeted the contralater...

journal_title：eLife

authors： Preston-Ferrer P,Coletta S,Frey M,Burgalossi A

更新日期：2016-06-10 00:00:00

abstract：:A broadly known method to stimulate the growth potential of axons is to elevate intracellular levels of cAMP, however the cellular pathway(s) that mediate this are not known. Here we identify the Dual Leucine-zipper Kinase (DLK, Wnd in Drosophila) as a critical target and effector of cAMP in injured axons. DLK/Wnd is ...

journal_title：eLife

authors： Hao Y,Frey E,Yoon C,Wong H,Nestorovski D,Holzman LB,Giger RJ,DiAntonio A,Collins C

更新日期：2016-06-07 00:00:00

abstract：:Complexin regulates spontaneous and activates Ca(2+)-triggered neurotransmitter release, yet the molecular mechanisms are still unclear. Here we performed single molecule fluorescence resonance energy transfer experiments and uncovered two conformations of complexin-1 bound to the ternary SNARE complex. In the cis con...

journal_title：eLife

authors： Choi UB,Zhao M,Zhang Y,Lai Y,Brunger AT

更新日期：2016-06-02 00:00:00

abstract：:The spliceosome is a complex machine composed of small nuclear ribonucleoproteins (snRNPs) and accessory proteins that excises introns from pre-mRNAs. After assembly the spliceosome is activated for catalysis by rearrangement of subunits to form an active site. How this rearrangement is coordinated is not well-underst...

journal_title：eLife

authors： Hoskins AA,Rodgers ML,Friedman LJ,Gelles J,Moore MJ

更新日期：2016-05-31 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：:Islet amyloidosis by IAPP contributes to pancreatic β-cell death in diabetes, but the nature of toxic IAPP species remains elusive. Using concurrent time-resolved biophysical and biological measurements, we define the toxic species produced during IAPP amyloid formation and link their properties to induction of rat IN...

journal_title：eLife

authors： Abedini A,Plesner A,Cao P,Ridgway Z,Zhang J,Tu LH,Middleton CT,Chao B,Sartori DJ,Meng F,Wang H,Wong AG,Zanni MT,Verchere CB,Raleigh DP,Schmidt AM

更新日期：2016-05-23 00:00:00

abstract：:A spring-loaded mechanism can explain the activation process for a protein that has a crucial role in maintaining the genomic integrity of immature eggs cells. ...

journal_title：eLife

authors： Amelio I,Melino G

更新日期：2016-05-23 00:00:00

abstract：:Advanced microscopy and labeling techniques reveal that bacteria localize mRNAs within their cells in a similar way to eukaryotes. ...

journal_title：eLife

authors： Jan CH

更新日期：2016-05-20 00:00:00

abstract：:PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory i...

journal_title：eLife

authors： Tsokas P,Hsieh C,Yao Y,Lesburguères E,Wallace EJC,Tcherepanov A,Jothianandan D,Hartley BR,Pan L,Rivard B,Farese RV,Sajan MP,Bergold PJ,Hernández AI,Cottrell JE,Shouval HZ,Fenton AA,Sacktor TC

更新日期：2016-05-17 00:00:00

abstract：:Burkholderia thailandensis uses acyl-homoserine lactone-mediated quorum sensing systems to regulate hundreds of genes. Here we show that cell-cell contact-dependent type VI secretion (T6S) toxin-immunity systems are among those activated by quorum sensing in B. thailandensis. We also demonstrate that T6S is required t...

journal_title：eLife

authors： Majerczyk C,Schneider E,Greenberg EP

更新日期：2016-05-16 00:00:00

abstract：:Certain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing 'leak...

journal_title：eLife

authors： Lutas A,Lahmann C,Soumillon M,Yellen G

更新日期：2016-05-13 00:00:00

abstract：:Mood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major depression. We show...

journal_title：eLife

authors： Gamble-George JC,Baldi R,Halladay L,Kocharian A,Hartley N,Silva CG,Roberts H,Haymer A,Marnett LJ,Holmes A,Patel S

更新日期：2016-05-10 00:00:00

abstract：:The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central n...

journal_title：eLife

authors： Amamoto R,Huerta VG,Takahashi E,Dai G,Grant AK,Fu Z,Arlotta P

更新日期：2016-05-09 00:00:00

abstract：:Duplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromosome reduplication occurs in many contexts, including: polytene t...

journal_title：eLife

authors： Stormo BM,Fox DT

更新日期：2016-05-09 00:00:00

abstract：:The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains t...

journal_title：eLife

authors： Isaac RS,Jiang F,Doudna JA,Lim WA,Narlikar GJ,Almeida R

更新日期：2016-04-28 00:00:00

abstract：:Translation is a core cellular process carried out by a highly conserved macromolecular machine, the ribosome. There has been remarkable evolutionary adaptation of this machine through the addition of eukaryote-specific ribosomal proteins whose individual effects on ribosome function are largely unknown. Here we show ...

journal_title：eLife

authors： Thompson MK,Rojas-Duran MF,Gangaramani P,Gilbert WV

更新日期：2016-04-27 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 NuRD complex is a multi-protein transcriptional corepressor that couples histone deacetylase and ATP-dependent chromatin remodelling activities. The complex regulates the higher-order structure of chromatin, and has important roles in the regulation of gene expression, DNA damage repair and cell differentiation. H...

journal_title：eLife

authors： Millard CJ,Varma N,Saleh A,Morris K,Watson PJ,Bottrill AR,Fairall L,Smith CJ,Schwabe JW

更新日期：2016-04-21 00:00:00

abstract：:The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a, that is enriched in colon cancer stem cells (CCSCs) and initi...

journal_title：eLife

authors： Wang L,Bu P,Ai Y,Srinivasan T,Chen HJ,Xiang K,Lipkin SM,Shen X

更新日期：2016-04-14 00:00:00

abstract：:The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG d...

journal_title：eLife

authors： Zahn R,Osmanović D,Ehret S,Araya Callis C,Frey S,Stewart M,You C,Görlich D,Hoogenboom BW,Richter RP

更新日期：2016-04-08 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：:Progression through the mitotic cell cycle requires periodic regulation of gene function at the levels of transcription, translation, protein-protein interactions, post-translational modification and degradation. However, the role of alternative splicing (AS) in the temporal control of cell cycle is not well understoo...

journal_title：eLife

authors： Dominguez D,Tsai YH,Weatheritt R,Wang Y,Blencowe BJ,Wang Z

更新日期：2016-03-25 00:00:00

abstract：:mTOR inhibition is beneficial in neurodegenerative disease models and its effects are often attributable to the modulation of autophagy and anti-apoptosis. Here, we report a neglected but important bioenergetic effect of mTOR inhibition in neurons. mTOR inhibition by rapamycin significantly preserves neuronal ATP leve...

journal_title：eLife

authors： Zheng X,Boyer L,Jin M,Kim Y,Fan W,Bardy C,Berggren T,Evans RM,Gage FH,Hunter T

更新日期：2016-03-23 00:00:00

abstract：:The organization and biophysical properties of the cytosol implicitly govern molecular interactions within cells. However, little is known about mechanisms by which cells regulate cytosolic properties and intracellular diffusion rates. Here, we demonstrate that the intracellular environment of budding yeast undertakes...

journal_title：eLife

authors： Joyner RP,Tang JH,Helenius J,Dultz E,Brune C,Holt LJ,Huet S,Müller DJ,Weis K

更新日期：2016-03-22 00:00:00

abstract：:Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis...

journal_title：eLife

authors： Lin TC,Su CY,Wu PY,Lai TC,Pan WA,Jan YH,Chang YC,Yeh CT,Chen CL,Ger LP,Chang HT,Yang CJ,Huang MS,Liu YP,Lin YF,Shyy JY,Tsai MD,Hsiao M

更新日期：2016-03-17 00:00:00

abstract：:Recent findings indicate a high level of specialization at the level of microcircuits and cell populations within brain structures with regards to the control of fear and anxiety. The hippocampus, however, has been treated as a unitary structure in anxiety and fear research despite mounting evidence that different hip...

journal_title：eLife

authors： Engin E,Smith KS,Gao Y,Nagy D,Foster RA,Tsvetkov E,Keist R,Crestani F,Fritschy JM,Bolshakov VY,Hajos M,Heldt SA,Rudolph U

更新日期：2016-03-14 00:00:00

abstract：:To improve chemical cross-linking of proteins coupled with mass spectrometry (CXMS), we developed a lysine-targeted enrichable cross-linker containing a biotin tag for affinity purification, a chemical cleavage site to separate cross-linked peptides away from biotin after enrichment, and a spacer arm that can be label...

journal_title：eLife

authors： Tan D,Li Q,Zhang MJ,Liu C,Ma C,Zhang P,Ding YH,Fan SB,Tao L,Yang B,Li X,Ma S,Liu J,Feng B,Liu X,Wang HW,He SM,Gao N,Ye K,Dong MQ,Lei X

更新日期：2016-03-08 00:00:00