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Author (up) Gong, M.; Chen, Bo.; Li, Z.-G.; Guo, L.-H. file  url
doi  openurl
  Title Heat-shock-induced cross adaptation to heat, chilling, drought and salt stress in maize seedlings and involvement of H2O2 Type Journal Article
  Year 2001 Publication Journal of Plant Physiology Abbreviated Journal Journal of Plant Physiology  
  Volume 158 Issue 9 Pages 1125-1130  
  Keywords cross adaptation; heat shock; hydrogen peroxide; Zea mays  
  Abstract A heat-shock pretreatment at 42 °C for 4 h followed by a 4-h recovery significantly enhanced survival rates of seedlings from two varieties of maize that differ in stress resistance. The procedure mitigated electrolyte leakage of primary roots and alleviated vitality loss of coleoptiles under severe heat, chilling, drought and salt stress, indicating that heat-shock pretreatment can induce cross adaptation. The heat-shock pretreatment, that induced cross adaptation, also produced an endogenous H2O2 peak in maize seedlings. Exogenous H2O2 treatments simultaneously enhanced multi-resistance to heat, chilling, drought and salt stress, implying that H2O2 may play a signalling role in triggering cross adaptation of maize seedlings to various stresses.  
  Call Number Serial 865  
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Author (up) Meltzer, H.Y.; Li, Z.; Kaneda, Y.; Ichikawa, J. file  url
openurl 
  Title Serotonin receptors: their key role in drugs to treat schizophrenia Type Journal Article
  Year 2003 Publication Progress in Neuro-Psychopharmacology & Biological Psychiatry Abbreviated Journal Prog Neuropsychopharmacol Biol Psychiatry  
  Volume 27 Issue 7 Pages 1159-1172  
  Keywords Animals; Antipsychotic Agents/*therapeutic use; Brain/drug effects/pathology; Dopamine/metabolism; Dopamine Agents/pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Humans; Receptors, Serotonin/classification/drug effects/*metabolism; Schizophrenia/*drug therapy; Serotonin Antagonists/therapeutic use; Serotonin Receptor Agonists/therapeutic use  
  Abstract Serotonin (5-HT)-receptor-based mechanisms have been postulated to play a critical role in the action of the new generation of antipsychotic drugs (APDs) that are usually referred to as atypical APDs because of their ability to achieve an antipsychotic effect with lower rates of extrapyramidal side effects (EPS) compared to first-generation APDs such as haloperidol. Specifically, it has been proposed by Meltzer et al. [J. Pharmacol. Exp. Ther. 251 (1989) 238] that potent 5-HT2A receptor antagonism together with weak dopamine (DA) D2 receptor antagonism are the principal pharmacologic features that differentiate clozapine and other apparent atypical APDs from first-generation typical APD. This hypothesis is consistent with the atypical features of quetiapine, olanzapine, risperidone, and ziprasidone, which are the most common treatments for schizophrenia in the United States and many other countries, as well as a large number of compounds in various stages of development. Subsequent research showed that 5-HT1A agonism may be an important consequence of 5-HT2A antagonism and that substitution of 5-HT1A agonism for 5-HT2A antagonism may also produce an atypical APD drug when coupled with weak D2 antagonism. Aripiprazole, the most recently introduced atypical APD, and a D2 receptor partial agonist, may also owe some of its atypical properties to its net effect of weak D2 antagonism, 5-HT2A antagonism and 5-HT1A agonism [Eur. J. Pharmacol. 441 (2002) 137]. By contrast, the alternative “fast-off” hypothesis of Kapur and Seeman [Am. J. Psychiatry 158 (2001) 360] applies only to clozapine and quetiapine and is inconsistent with the “slow” off rate of most atypical APDs, including olanzapine, risperidone and ziprasidone. 5-HT2A and 5-HT1A receptors located on glutamatergic pyramidal neurons in the cortex and hippocampus, 5-HT2A receptors on the cell bodies of DA neurons in the ventral tegmentum and substantia nigra and GABAergic interneurons in the cortex and hippocampus, and 5-HT1A receptors in the raphe nuclei are likely to be important sites of action of the atypical APDs. At the same time, evidence has accumulated for the important modulatory role of 5-HT2C and 5-HT6 receptors for some of the effects of some of the current APDs. Thus, 5-HT has joined DA as a critical target for developing effective APDs and led to the search for novel drugs with complex pharmacology, ending the exclusive search for single-receptor targets, e.g., the D3 or D4 receptor, and drugs that are selective for them.  
  Call Number Serial 1154  
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Author (up) Parsons, A.B.; Brost, R.L.; Ding, H.; Li, Z.; Zhang, C.; Sheikh, B.; Brown, G.W.; Kane, P.M.; Hughes, T.R.; Boone, C. file  url
doi  openurl
  Title Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways Type Journal Article
  Year 2004 Publication Nature Biotechnology Abbreviated Journal Nat Biotechnol  
  Volume 22 Issue 1 Pages 62-69  
  Keywords Biotechnology/*methods; Cluster Analysis; Drug Industry/*methods; *Drug Resistance; Fungal Proteins/metabolism; Gene Deletion; *Gene Expression Regulation; Mutation; Pharmacogenetics; Proton-Translocating ATPases/metabolism; Saccharomyces cerevisiae/*genetics; Software  
  Abstract Bioactive compounds can be valuable research tools and drug leads, but it is often difficult to identify their mechanism of action or cellular target. Here we investigate the potential for integration of chemical-genetic and genetic interaction data to reveal information about the pathways and targets of inhibitory compounds. Taking advantage of the existing complete set of yeast haploid deletion mutants, we generated drug-hypersensitivity (chemical-genetic) profiles for 12 compounds. In addition to a set of compound-specific interactions, the chemical-genetic profiles identified a large group of genes required for multidrug resistance. In particular, yeast mutants lacking a functional vacuolar H(+)-ATPase show multidrug sensitivity, a phenomenon that may be conserved in mammalian cells. By filtering chemical-genetic profiles for the multidrug-resistant genes and then clustering the compound-specific profiles with a compendium of large-scale genetic interaction profiles, we were able to identify target pathways or proteins. This method thus provides a powerful means for inferring mechanism of action.  
  Call Number Serial 339  
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Author (up) Zhao, J.; Ma, J.; Deng, Y.; Kelly, J.A.; Kim, K.; Bang, S.-Y.; Lee, H.-S.; Li, Q.-Z.; Wakeland, E.K.; Qiu, R.; Liu, M.; Guo, J.; Li, Z.; Tan, W.; Rasmussen, A.; Lessard, C.J.; Sivils, K.L.; Hahn, B.H.; Grossman, J.M.; Kamen, D.L.; Gilkeson, G.S.; Bae, S.-C.; Gaffney, P.M.; Shen, N.; Tsao, B.P. file  url
openurl 
  Title A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases Type Journal Article
  Year 2017 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 49 Issue 3 Pages 433-437  
  Keywords  
  Abstract Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type I interferon signature. Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47phox subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the Immunochip in the GTF2IRD1-GTF2I region at 7q11.23 with a complex genomic structure. We show that the p.Arg90His substitution, which is reported to cause reduced reactive oxygen species (ROS) production, predisposes to SLE (odds ratio (OR) = 3.47 in Asians (Pmeta = 3.1 x 10-104), OR = 2.61 in European Americans, OR = 2.02 in African Americans) and other autoimmune diseases, including primary Sjogren's syndrome (OR = 2.45 in Chinese, OR = 2.35 in European Americans) and rheumatoid arthritis (OR = 1.65 in Koreans). Additionally, decreased and increased copy numbers of NCF1 predispose to and protect against SLE, respectively. Our data highlight the pathogenic role of reduced NOX2-derived ROS levels in autoimmune diseases.  
  Call Number Serial 1768  
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