Additivity of mutant effects assessed by binomial mutagenesis.

abstract：:Canavan's disease (CD) is a fatal, hereditary disorder of CNS development that has been linked to mutations in the gene for the enzyme aspartoacylase (ASPA) (EC 3.5.1.15). ASPA acts to hydrolyze N-acetylaspartate (NAA) into l-aspartate and acetate, but the connection between ASPA deficiency and the failure of proper C...

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

authors： Madhavarao CN,Arun P,Moffett JR,Szucs S,Surendran S,Matalon R,Garbern J,Hristova D,Johnson A,Jiang W,Namboodiri MA

更新日期：2005-04-05 00:00:00

abstract：:As a master regulator of functional Ig heavy chain (IgH) expression, the IgH 3' regulatory region (3'RR) controls multiple transcription events at various stages of B-cell ontogeny, from newly formed B cells until the ultimate plasma cell stage. The IgH 3'RR plays a pivotal role in early B-cell receptor expression, ge...

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

authors： Garot A,Marquet M,Saintamand A,Bender S,Le Noir S,Rouaud P,Carrion C,Oruc Z,Bébin AG,Moreau J,Lebrigand K,Denizot Y,Alt FW,Cogné M,Pinaud E

更新日期：2016-02-09 00:00:00

abstract：:The human renin gene was isolated from a Charon 4A human genomic library and characterized. The gene spans about 11.7 kilobases and consists of 10 exons and 9 introns that map at points that could be variable surface loops of the enzyme. The complete coding regions, the 5'- and 3'-flanking regions, and the exon-intron...

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

authors： Miyazaki H,Fukamizu A,Hirose S,Hayashi T,Hori H,Ohkubo H,Nakanishi S,Murakami K

更新日期：1984-10-01 00:00:00

abstract：:Collective animal behavior studies have led the way in developing models that account for a large number of individuals, but mostly have considered situations in which alignment and attraction play a key role, such as in schooling and flocking. By quantifying how animals react to one another's presence, when interacti...

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

authors： Giuggioli L,Potts JR,Rubenstein DI,Levin SA

更新日期：2013-10-15 00:00:00

abstract：:The human epidermal growth factor receptor 2 (HER2) is specifically overexpressed in tumors of several cancers, including an aggressive form of breast cancer. It is therefore a target for both cancer diagnostics and therapy. The 58 amino acid residue Zher2 affibody molecule was previously engineered as a high-affinity...

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

authors： Eigenbrot C,Ultsch M,Dubnovitsky A,Abrahmsén L,Härd T

更新日期：2010-08-24 00:00:00

abstract：:Autophagy, a conserved pathway that delivers intracellular materials into lysosomes for degradation, is involved in development, aging, and a variety of diseases. Accumulating evidence demonstrates that autophagy plays a protective role against infectious diseases by diminishing intracellular pathogens, including bact...

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

authors： Zou CG,Ma YC,Dai LL,Zhang KQ

更新日期：2014-08-26 00:00:00

abstract：:Hypnotic analgesia in some respects resembles opiate analgesia. We tested the hypothesis that some features of hypnotic analgesia are mediated through neuronal pathways activating specific opiate receptors in brain. The opiate antagonist naloxone had no effect on hypnotic analgesia in three subjects. Thus, the hypothe...

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

authors： Goldstein A,Hilgard ER

更新日期：1975-06-01 00:00:00

abstract：:Monoclonal antibodies (mAbs) against purified human placental insulin-like growth factor I (IGF-I) receptors were prepared and characterized. Three IgG mAbs were specific for the human IGF-I receptor and displayed negligible crossreactivity with the human insulin receptor. They stimulated 125I-labeled IGF-I (125I-IGF-...

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

authors： Xiong L,Kasuya J,Li SL,Kato J,Fujita-Yamaguchi Y

更新日期：1992-06-15 00:00:00

abstract：:Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to...

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

authors： Weir PT,Dickinson MH

更新日期：2015-10-06 00:00:00

abstract：:The peripheral axonal branch of primary sensory neurons readily regenerates after peripheral nerve injury, but the central branch, which courses in the dorsal columns of the spinal cord, does not. However, if a peripheral nerve is transected before a spinal cord injury, sensory neurons that course in the dorsal column...

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

authors： Neumann S,Skinner K,Basbaum AI

更新日期：2005-11-15 00:00:00

abstract：:Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with regulation of the L-type Ca2(+)-channel current (ICa) through the opposite actions of two second messengers, cyclic AMP and cyclic GMP. While cyclic AMP stimulation of ICa is mediated by the activation of cyclic AMP-dependent ...

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

authors： Méry PF,Lohmann SM,Walter U,Fischmeister R

更新日期：1991-02-15 00:00:00

abstract：:It was proved that the protoplasts prepared from mesophyll of Nicotiana tabacum are infected by tobacco mosaic virus. The infection occurred when purified tobacco mosaic virus particles were added to a protoplast suspension in the presence of poly-L-ornithine. The virus multiplied in these protoplasts to a level of 10...

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

authors： Takebe I,Otsuki Y

更新日期：1969-11-01 00:00:00

abstract：:Cellular senescence is defined by the limited proliferative capacity of normal cultured cells. Immortal cells overcome this regulation and proliferate indefinitively. One step in the immortalization process may be reactivation of telomerase activity, a ribonucleoprotein complex, which, by de novo synthesized telomeric...

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

authors： Härle-Bachor C,Boukamp P

更新日期：1996-06-25 00:00:00

abstract：:Based on the DNA sequence of the symbiotic plasmid of Rhizobium strain NGR234, we predicted potential rearrangements generated by homologous recombination. All predicted rearrangements were identified experimentally by using a PCR-based methodology. Thus, the predicted and the actual dynamic maps of the replicon coinc...

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

authors： Flores M,Mavingui P,Perret X,Broughton WJ,Romero D,Hernández G,Dávila G,Palacios R

更新日期：2000-08-01 00:00:00

abstract：:Notwithstanding important advances in the context of single-variant pathogenicity identification, novel breakthroughs in discerning the origins of many rare diseases require methods able to identify more complex genetic models. We present here the Variant Combinations Pathogenicity Predictor (VarCoPP), a machine-learn...

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

authors： Papadimitriou S,Gazzo A,Versbraegen N,Nachtegael C,Aerts J,Moreau Y,Van Dooren S,Nowé A,Smits G,Lenaerts T

更新日期：2019-06-11 00:00:00

abstract：:During latent infection of humans with Mycobacterium tuberculosis, bacteria persist in the asymptomatic host within granulomas, organized collections of differentiated macrophages, and other immune cells. The mechanisms for persistence remain poorly understood, as is the metabolic and replicative state of the microbes...

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

authors： Chan K,Knaak T,Satkamp L,Humbert O,Falkow S,Ramakrishnan L

更新日期：2002-03-19 00:00:00

abstract：:Rat liver polysomal RNA was translated in the rabbit reticulocyte lysate and in the wheat germ cell-free protein-synthesizing systems, using [(35)S]methionine as label. The catalase (hydrogen-peroxide:hydrogen-peroxide oxidoreductase, EC 1.11.1.6) that was synthesized was isolated by immunoprecipitation and characteri...

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

authors： Robbi M,Lazarow PB

更新日期：1978-09-01 00:00:00

abstract：:We have identified a major T-cell epitope, amino acids 48-54 (DRAHYNI, in one-letter code) in the E7 open reading frame protein of human papillomavirus (HPV) type 16. Lymph node cells from mice immunized with synthetic peptides containing DRAHYNI proliferated and produced interleukin when challenged in vitro with pept...

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

authors： Tindle RW,Fernando GJ,Sterling JC,Frazer IH

更新日期：1991-07-01 00:00:00

abstract：:Significant attention has focused on the role of low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis. However, recent advances have identified triglyceride-rich lipoproteins [e.g., very LDL (VLDL)] as independent risk predictors for this disease. We have previously demonstrated peroxisome proliferator...

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

authors： Lee CH,Kang K,Mehl IR,Nofsinger R,Alaynick WA,Chong LW,Rosenfeld JM,Evans RM

更新日期：2006-02-14 00:00:00

abstract：:Chronic hypoxia causes pulmonary hypertension with smooth muscle cell proliferation and matrix deposition in the wall of the pulmonary arterioles. We demonstrate here that hypoxia also induces a pronounced inflammation in the lung before the structural changes of the vessel wall. The proinflammatory action of hypoxia ...

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

authors： Minamino T,Christou H,Hsieh CM,Liu Y,Dhawan V,Abraham NG,Perrella MA,Mitsialis SA,Kourembanas S

更新日期：2001-07-17 00:00:00

abstract：:O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. OGT participates in transcriptional and epigenetic regulation, and dysregulation of OGT has been implicated in diseases such as cancer. However, t...

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

authors： Chu CS,Lo PW,Yeh YH,Hsu PH,Peng SH,Teng YC,Kang ML,Wong CH,Juan LJ

更新日期：2014-01-28 00:00:00

abstract：:In most human follicular B cell lymphomas the bcl-2 gene is up-regulated as a result of the t(14;18) chromosomal translocation generating a hybrid bcl-2-IgH mRNA. Recently, we have identified in t(14;18)-positive cells a bcl-2-IgH mRNA in the antisense orientation, putatively responsible for the overexpression of bcl-...

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

authors： Morelli S,Delia D,Capaccioli S,Quattrone A,Schiavone N,Bevilacqua A,Tomasini S,Nicolin A

更新日期：1997-07-22 00:00:00

abstract：:Although in decline after successful anti-HIV therapy, B-cell lymphomas are still elevated in HIV-1-seropositive (HIV+) persons, and the mechanisms are obscure. The HIV-1 matrix protein p17 persists in germinal centers long after HIV-1 drug suppression, and some p17 variants (vp17s) activate Akt signaling and promote ...

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

authors： Dolcetti R,Giagulli C,He W,Selleri M,Caccuri F,Eyzaguirre LM,Mazzuca P,Corbellini S,Campilongo F,Marsico S,Giombini E,Muraro E,Rozera G,De Paoli P,Carbone A,Capobianchi MR,Ippolito G,Fiorentini S,Blattner WA,Lu W,

更新日期：2015-11-17 00:00:00

abstract：:We have studied the properties of r-eag voltage-activated potassium channels in a stably transfected human embryonic kidney cell line. It was found that r-eag channels are rapidly and reversibly inhibited by a rise in intracellular calcium from 30 to 300 nM. The inhibition does not appear to depend on the activity of ...

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

authors： Stansfeld CE,Röper J,Ludwig J,Weseloh RM,Marsh SJ,Brown DA,Pongs O

更新日期：1996-09-03 00:00:00

abstract：:Amino-terminal sequence determinations are reported of the subunits of biliproteins of prokaryotic unicellular and filamentous cyanobacteria and of eukaryotic unicellular red algae. The biliproteins examined, allophycocyanin, C-phycocyanin, R-phycocyanin, b-phycoerythrin, and phycoerythrocyanin, vary with respect to t...

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

authors： Glazer AN,Apell GS,Hixson CS,Bryant DA,Rimon S,Brown DM

更新日期：1976-02-01 00:00:00

abstract：:A mitochondrial gene from Saccharomyces cerevisiae encoding a hydrophobic membrane protein, subunit 8 of the F0/F1-type mitochondrial ATPase complex, has been functionally replaced by an artificial nuclear gene specifying an imported version of this protein. The experiments reported here utilized a multicopy expressio...

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

authors： Nagley P,Farrell LB,Gearing DP,Nero D,Meltzer S,Devenish RJ

更新日期：1988-04-01 00:00:00

abstract：:There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the...

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

authors： Oliver JD,Sibley GEM,Beckmann N,Dobb KS,Slater MJ,McEntee L,du Pré S,Livermore J,Bromley MJ,Wiederhold NP,Hope WW,Kennedy AJ,Law D,Birch M

更新日期：2016-11-08 00:00:00

abstract：:Vanilloid receptor subunit 1 (VR1) appears to play a critical role in the transduction of noxious chemical and thermal stimuli by sensory nerve endings in peripheral tissues. Thus, VR1 antagonists are useful compounds to unravel the contribution of this receptor to pain perception, as well as to induce analgesia. We h...

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

authors： García-Martinez C,Humet M,Planells-Cases R,Gomis A,Caprini M,Viana F,De La Pena E,Sanchez-Baeza F,Carbonell T,De Felipe C,Pérez-Paya E,Belmonte C,Messeguer A,Ferrer-Montiel A

更新日期：2002-02-19 00:00:00

abstract：:Trypanosomatid RNA editing is a unique process and essential for these organisms. It therefore represents a drug target for a group of protozoa that includes the causative agents for African sleeping sickness and other devastating tropical and subtropical diseases. Here, we present drug-like inhibitors of a key enzyme...

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

authors： Amaro RE,Schnaufer A,Interthal H,Hol W,Stuart KD,McCammon JA

更新日期：2008-11-11 00:00:00

abstract：:Albumin Redhill is an electrophoretically slow genetic variant of human serum albumin that does not bind 63Ni2+ and has a molecular mass 2.5 kDa higher than normal albumin. Its inability to bind Ni2+ was explained by the finding of an additional residue of Arg at position -1. This did not explain the molecular basis o...

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

authors： Brennan SO,Myles T,Peach RJ,Donaldson D,George PM

更新日期：1990-01-01 00:00:00