Allosteric regulation of γ-secretase activity by a phenylimidazole-type γ-secretase modulator.

abstract：:We studied the surface delivery pathways followed by newly synthesized plasma membrane proteins in intestinal cells. To this end, we developed an assay and characterized an epithelial cell line (SK-CO-15) derived from human colon adenocarcinoma. Polarized confluent monolayers (2000 omega.cm2), grown on polycarbonate f...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Le Bivic A,Real FX,Rodriguez-Boulan E

更新日期：1989-12-01 00:00:00

abstract：:MicroRNAs are predicted to regulate approximately 30% of all human genes by targeting sequences in their 3' UTR. Polymorphisms in 3' UTR of several genes have been reported to affect gene expression, but the mechanism is not fully understood. Here, we demonstrate that 829C-->T, a naturally occurring SNP, near the miR-...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Mishra PJ,Humeniuk R,Mishra PJ,Longo-Sorbello GS,Banerjee D,Bertino JR

更新日期：2007-08-14 00:00:00

abstract：:We have previously shown that mammary epithelial specific expression of the activated erbB2 allele under the control of the endogenous promoter in mice resulted in the formation of mammary adenocarcinomas. To assess whether mammary tumorigenesis in this model is influenced by the developmental window of expression, we...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Andrechek ER,Hardy WR,Laing MA,Muller WJ

更新日期：2004-04-06 00:00:00

abstract：:The oxygenation of the atmosphere ∼2.45-2.32 billion years ago (Ga) is one of the most significant geological events to have affected Earth's redox history. Our understanding of the timing and processes surrounding this key transition is largely dependent on the development of redox-sensitive proxies, many of which re...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Chi Fru E,Rodríguez NP,Partin CA,Lalonde SV,Andersson P,Weiss DJ,El Albani A,Rodushkin I,Konhauser KO

更新日期：2016-05-03 00:00:00

abstract：:Human skin and lung mast cells and rodent peritoneal mast cells contain a carboxypeptidase in their secretory granules. We have screened human lung cDNA libraries with a mouse mast cell carboxypeptidase A (MC-CPA) cDNA probe to isolate a near-full-length cDNA that encodes human MC-CPA. The 5' end of the human MC-CPA t...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Reynolds DS,Gurley DS,Stevens RL,Sugarbaker DJ,Austen KF,Serafin WE

更新日期：1989-12-01 00:00:00

abstract：:Through a multiplex promoter spanning 218 kb, the phase II UDP-glucuronosyltransferase 1A (UGT1) gene encodes at least eight differently regulated mRNAs whose protein products function as the principal means to eliminate a vast array of steroids, heme metabolites, environmental toxins, and drugs. The orphan nuclear re...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Xie W,Yeuh MF,Radominska-Pandya A,Saini SP,Negishi Y,Bottroff BS,Cabrera GY,Tukey RH,Evans RM

更新日期：2003-04-01 00:00:00

abstract：:The suprachiasmatic nucleus (SCN), the master circadian clock in mammals, sends major output signals to the subparaventricular zone (SPZ) and further to the paraventricular nucleus (PVN), the neural mechanism of which is largely unknown. In this study, the intracellular calcium levels were measured continuously in cul...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Wu YE,Enoki R,Oda Y,Huang ZL,Honma KI,Honma S

更新日期：2018-10-02 00:00:00

abstract：:Human settlement of Polynesia was a major event in world prehistory. Despite the vastness of the distances covered, research suggests that prehistoric Polynesian populations maintained spheres of continuing interaction for at least some period of time in some regions. A low level of genetic variation in ancestral Poly...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Matisoo-Smith E,Roberts RM,Irwin GJ,Allen JS,Penny D,Lambert DM

更新日期：1998-12-08 00:00:00

abstract：:The ciliary epithelium in the eye consists of pigmented epithelial cells that express the α1β1 isoform of Na,K-ATPase and nonpigmented epithelial cells that express mainly the α2β3 isoform. In principle, a Na,K-ATPase inhibitor with selectivity for α2β3 that penetrates the cornea could effectively reduce intraocular p...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Katz A,Tal DM,Heller D,Habeck M,Ben Zeev E,Rabah B,Bar Kana Y,Marcovich AL,Karlish SJ

更新日期：2015-11-03 00:00:00

abstract：:Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Understanding the distinct genetic and epigenetic changes contributing to the establishment and growth of metastatic lesions is crucial for the development of novel therapeutic strategies. In a search for key regulators of col...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Rychahou PG,Kang J,Gulhati P,Doan HQ,Chen LA,Xiao SY,Chung DH,Evers BM

更新日期：2008-12-23 00:00:00

abstract：:A sensitive assay using biotinylated ubiquitin revealed extensive ubiquitination of the large subunit of RNA polymerase II during incubations of transcription reactions in vitro. Phosphorylation of the repetitive carboxyl-terminal domain of the large subunit was a signal for ubiquitination. Specific inhibitors of cycl...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Mitsui A,Sharp PA

更新日期：1999-05-25 00:00:00

abstract：:Type I and type III IFNs bind to different cell-surface receptors but induce identical signal transduction pathways, leading to the expression of antiviral host effector molecules. Despite the fact that type III IFN (IFN-λ) has been shown to predominantly act on mucosal organs, in vivo infection studies have failed to...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Pott J,Mahlakõiv T,Mordstein M,Duerr CU,Michiels T,Stockinger S,Staeheli P,Hornef MW

更新日期：2011-05-10 00:00:00

abstract：:The lateral neural plate border (NPB), the neural part of the vertebrate neural border, is composed of central nervous system (CNS) progenitors and peripheral nervous system (PNS) progenitors. In invertebrates, PNS progenitors are also juxtaposed to the lateral boundary of the CNS. Whether there are conserved molecula...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Li Y,Zhao D,Horie T,Chen G,Bao H,Chen S,Liu W,Horie R,Liang T,Dong B,Feng Q,Tao Q,Liu X

更新日期：2017-08-01 00:00:00

abstract：:Recent findings intriguingly place DNA double-strand break repair proteins at chromosome ends in yeast, where they help maintain normal telomere length and structure. In the present study, an essential telomere function, the ability to cap and thereby protect chromosomes from end-to-end fusions, was assessed in repair...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Bailey SM,Meyne J,Chen DJ,Kurimasa A,Li GC,Lehnert BE,Goodwin EH

更新日期：1999-12-21 00:00:00

abstract：:Retrograde axonal transport plays an important role in the maintenance of neuronal functions, but the mechanism is poorly defined partly because the constituents of the retrograde transport system and their interactions have yet to be elucidated. Of special interest is how dynein/dynactin motor proteins interact with ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Liu JJ,Ding J,Wu C,Bhagavatula P,Cui B,Chu S,Mobley WC,Yang Y

更新日期：2007-02-13 00:00:00

abstract：:Evolutionary thinking can be applied to both cultural microevolution and macroevolution. However, much of the current literature focuses on cultural microevolution. In this article, we argue that the growing availability of large cross-cultural datasets facilitates the use of computational methods derived from evoluti...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Gray RD,Watts J

更新日期：2017-07-25 00:00:00

abstract：:The hammerhead ribozyme, as engineered by J. Haseloff and W. L. Gerlach [(1988) Nature (London) 334, 585-591], is an RNA molecule containing two regions of conserved nucleotides, a double helix, called helix II, which connects the two conserved regions, and flanking arms of variable sequence, which hybridize the riboz...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： McCall MJ,Hendry P,Jennings PA

更新日期：1992-07-01 00:00:00

abstract：:The positions of transition states along reaction coordinates (r++) for simple chemical reactions are often estimated from Leffler alpha values, the slope of plots of DeltaG++ (activation energy) versus DeltaG(0) (equilibrium free energy) for a series of structural variants. Protein folding is more complex than simple...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Fersht AR

更新日期：2004-10-05 00:00:00

abstract：:The mechanism of phospholipase C regulation by inhibitory receptors was analyzed both in intact and in permeabilized rat thyroid cells (FRTL5). In this system, the muscarinic agonist carbachol inhibited phospholipase C, as indicated by the decrease in the basal levels of inositol 1,4,5-trisphosphate as well as by the ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Bizzarri C,Di Girolamo M,D'Orazio MC,Corda D

更新日期：1990-06-01 00:00:00

abstract：:Cones show briefer light responses than rods and do not saturate even under very bright light. Using purified rod and cone homogenates, we measured the activity of guanylate cyclase (GC), an enzyme responsible for cGMP synthesis and therefore recovery of a light response. The basal GC activity was 36 times higher in c...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Takemoto N,Tachibanaki S,Kawamura S

更新日期：2009-07-14 00:00:00

abstract：:The highly aggressive character of melanoma makes it an excellent model for probing the mechanisms underlying metastasis, which remains one of the most difficult challenges in treating cancer. We find that miR-182, member of a miRNA cluster in a chromosomal locus (7q31-34) frequently amplified in melanoma, is commonly...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Segura MF,Hanniford D,Menendez S,Reavie L,Zou X,Alvarez-Diaz S,Zakrzewski J,Blochin E,Rose A,Bogunovic D,Polsky D,Wei J,Lee P,Belitskaya-Levy I,Bhardwaj N,Osman I,Hernando E

更新日期：2009-02-10 00:00:00

abstract：:Receptor tyrosine kinases (RTKs) are a class of cell surface receptors that, upon ligand binding, stimulate a variety of critical cellular functions. The orphan receptor anaplastic lymphoma kinase (ALK) is one of very few RTKs that remain without a firmly established protein ligand. Here we present a novel cytokine, F...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Reshetnyak AV,Murray PB,Shi X,Mo ES,Mohanty J,Tome F,Bai H,Gunel M,Lax I,Schlessinger J

更新日期：2015-12-29 00:00:00

abstract：:PTP1C, a protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) containing two src homology 2 domains, is poorly active when assayed with various protein substrates in vitro. Its activity is stimulated > 1000-fold by anionic phospholipids when myelin basic protein or mitogen-activated ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Zhao Z,Shen SH,Fischer EH

更新日期：1993-05-01 00:00:00

abstract：:Complex I functions as a redox-linked proton pump in the respiratory chains of mitochondria and bacteria, driven by the reduction of quinone (Q) by NADH. Remarkably, the distance between the Q reduction site and the most distant proton channels extends nearly 200 Å. To elucidate the molecular origin of this long-range...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Sharma V,Belevich G,Gamiz-Hernandez AP,Róg T,Vattulainen I,Verkhovskaya ML,Wikström M,Hummer G,Kaila VR

更新日期：2015-09-15 00:00:00

abstract：:Although Wingless (Wg)/Wnt signaling has been implicated in heart development of multiple organisms, conflicting results have been reported regarding the role of Wnt/beta-catenin pathway in cardiac myogenesis: Wg/armadillo signaling promotes heart development in Drosophila, whereas activation of Wnt/beta-catenin signa...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Naito AT,Shiojima I,Akazawa H,Hidaka K,Morisaki T,Kikuchi A,Komuro I

更新日期：2006-12-26 00:00:00

abstract：:The Japanese firefly squid, Watasenia scintillans, emits intense flashes of light from three tiny luminous organs that are located at the tip of each of a pair of ventral arms. Light is also produced from hundreds of other minute organs that are scattered over the body. The luminescence is due to an ATP-dependent reac...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Tsuji FI

更新日期：1985-07-01 00:00:00

abstract：:Size has a profound effect on the structure of the brain. Many brain structures scale allometrically, that is, their relative size changes systematically as a function of brain size. Here we use independent contrasts analysis to examine the scaling of frontal cortex in 43 species of mammals including 25 primates and 1...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Bush EC,Allman JM

更新日期：2004-03-16 00:00:00

abstract：:The role of Notch signaling in cartilage differentiation and maturation in vivo was examined. Conditional Notch pathway gain and loss of function was achieved using a Cre/loxP approach to manipulate Notch signaling in cartilage precursors and chondrocytes of the developing mouse embryo. Conditional overexpression of a...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Mead TJ,Yutzey KE

更新日期：2009-08-25 00:00:00

abstract：:Gene function is typically evaluated by sampling the continuum of gene expression at only a few discrete points corresponding to gene knockout or overexpression. We argue that this characterization is incomplete and present a library of engineered promoters of varying strengths obtained through mutagenesis of a consti...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Alper H,Fischer C,Nevoigt E,Stephanopoulos G

更新日期：2005-09-06 00:00:00

abstract：:Epidemiological and genetic association studies show that genetics play an important role in the attainment of education. Here, we investigate the effect of this genetic component on the reproductive history of 109,120 Icelanders and the consequent impact on the gene pool over time. We show that an educational attainm...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Kong A,Frigge ML,Thorleifsson G,Stefansson H,Young AI,Zink F,Jonsdottir GA,Okbay A,Sulem P,Masson G,Gudbjartsson DF,Helgason A,Bjornsdottir G,Thorsteinsdottir U,Stefansson K

更新日期：2017-01-31 00:00:00