The Experts below are selected from a list of 852 Experts worldwide ranked by ideXlab platform
Michael D. Topal - One of the best experts on this subject based on the ideXlab platform.
-
structure of naei dna complex reveals dual mode dna recognition and complete dimer rearrangement
Nature Structural & Molecular Biology, 2001Co-Authors: Qing Huai, James D Colandene, Michael D. TopalAbstract:NaeI, a novel DNA endonuclease, shows topoisomerase and recombinase activities when a Lys residue is substituted for Leu 43. The NaeI-DNA structure demonstrates that each of the two domains of NaeI recognizes one molecule of DNA duplex. DNA recognition induces dramatic rearrangements: narrowing the binding site of the Topo domain 16 A to grip DNA, widening that of the Endo domain 8 A to encircle and bend DNA 45 degrees for cleavage, and completely rebuilding the homodimer interface. The NaeI-DNA structure presents the first example of novel recognition of two copies of one DNA sequence by two different amino acid sequences and two different structural motifs in one polypeptide.
-
changing a leucine to a lysine residue makes naei endonuclease hypersensitive to dna intercalative drugs
Biochemistry, 1996Co-Authors: Kiwon Jo, Michael D. TopalAbstract:: A single amino acid change transforms restriction enzyme NaeI to a topoisomerase and recombinase (NaeI-L43K) that shows no sequence similarity to these protein families. This transformation appears to result from coupled endonuclease and ligase domains. To further elucidate the relationship between NaeI-L43K and the topoisomerase protein family, we studied the effect of the topoisomerase inhibitors on NaeI-L43K activity. The intercalative drugs amsacrine, ellipticine, and daunorubicin inhibited NaeI-L43K, whereas the nonintercalating drugs camptothecin, VP-16, and oxolinic acid did not. Ethidium bromide also inhibited NaeI-L43K, implying that intercalation is responsible for its inhibition. The effects of the intercalative drugs on the DNA cleavage steps of NaeI and NaeI-L43K were compared. The drugs hardly inhibited DNA cleavage by wild type NaeI but completely inhibited DNA cleavage by NaeI-L43K. This difference in inhibition demonstrates that the L43K amino acid change sensitized NaeI to these drugs. Low concentrations of the intercalative drugs, except for ethidium bromide, enhance production of topoisomerase--DNA covalent intermediates but inhibited production of the NaeI-L43K--DNA covalent intermediate. These results imply some unique differences between DNA relaxation by NaeI-L43K and DNA topoisomerase. Concomitant with studying inhibition of the cleavage intermediate, NaeI-L43K was found to covalently bond with the 5' end of the cleaved DNA strand.
-
Ability of DNA and spermidine to affect the activity of restriction endonucleases from several bacterial species.
Biochemistry, 1991Co-Authors: Adriana R. Oller, Willem Vanden Broek, Michael J. Conrad, Michael D. TopalAbstract:Previous work has described the novel ability to modulate in vitro the activity of restriction endonuclease NaeI from Nocardia aerocoligenes by using cleavable DNA and spermidine [Conrad & Topal (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 9707-9711]. In this paper we report the results of a study of 49 type II restriction enzymes from a variety of bacterial species. On the basis of the rates of cleavage observed, we found that in addition to expected cleavable sites a number of enzymes had slow and resistant cognate recognition sites. Resistant sites were identified for BspMI, NaeI, and NarI; slow sites were identified for HpaII, NaeI, and SacII. Cleavage of these sites was found to be significantly enhanced by the addition of cleavable DNA or spermidine. We demonstrate that for BspMI, as for NaeI, activator DNAs increased Vmax without altering Km, whereas for HpaII, NarI, and SacII activator DNAs decreased Km without changing Vmax. Comparison among the Kms for NaeI cleavage of several different substrates demonstrated that distant DNA sequences can affect DNA recognition by the activated enzyme. Our observations extend DNA activation of the Nocardia NaeI endonuclease to restriction endonucleases from Nocardia argentinensis (NarI), Bacillus species M (BspMI), Haemophilus parainfluenza (HpaII), and Streptomyces achromogenes (SacII). In addition, activation has now been found to affect slow as well as resistant recognition sites.
-
naei endonuclease binding to pbr322 dna induces looping
Biochemistry, 1991Co-Authors: Michael D. Topal, Michael J. Conrad, Randy J Thresher, Jack D GriffithAbstract:: Previous work has demonstrated the existence of both resistant and cleavable NaeI sites. Cleavable sites introduced on exogenous DNA can act in trans to increase the catalysis of NaeI endonuclease cleavage at resistant sites without affecting the apparent binding affinity of the enzyme for the resistant site [Conrad, M., & Topal, M. D. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 9707-9711]. This activation suggests allosteric regulation of NaeI cleavage by distant cis- and trans-acting sites in DNAs containing both resistant and cleavable sites. Plasmid pBR322 contains four NaeI sites, at least one of which is resistant to cleavage. Electron microscopy is used here to demonstrate that NaeI endonuclease simultaneously binds to multiple recognition sites in pBR322 DNA to form loops with NaeI protein bound at the loop's base. The maximum number of loops formed with a common base suggests four binding sites per enzyme molecule. Looping was inhibited by addition of enzyme-saturating amounts of double-stranded oligonucleotide containing an NaeI site, whereas another double-strand oligonucleotide without the NaeI site had no effect. The number of loops seen was not above background when double-stranded M13 DNA, which contains only a single NaeI recognition site, was used as substrate.
Gary M Williams - One of the best experts on this subject based on the ideXlab platform.
-
n nitrosodiethylamine mechanistic data and risk assessment bioactivation dna adduct formation mutagenicity and tumor initiation
Pharmacology & Therapeutics, 1996Co-Authors: Lynne Verna, John Whysner, Gary M WilliamsAbstract:Abstract N-Nitrosodiethylamine (NDEA) is DNA reactive after bioactivation and produces tumors in every animal species tested. Bioactivation is effected by several P450 isozymes including CYP2E1, which is ethanol inducible. Tumor formation in rat liver was proportional to O 4 -ethyldeoxythymidine formation in DNA, which was generally proportional to NDEA dose. At low doses in the 0.033–1.1 ppm range, the doseresponse for esophageal tumor formation was sublinear, possibly due to DNA repair. Although no epidemiological studies have specifically evaluated NDEA, sufficient exposure levels would be expected to cause cancer in humans.
-
n nitrosodiethylamine mechanistic data and risk assessment bioactivation dna adduct formation mutagenicity and tumor initiation
Pharmacology & Therapeutics, 1996Co-Authors: Lynne Verna, John Whysner, Gary M WilliamsAbstract:Abstract N-Nitrosodiethylamine (NDEA) is DNA reactive after bioactivation and produces tumors in every animal species tested. Bioactivation is effected by several P450 isozymes including CYP2E1, which is ethanol inducible. Tumor formation in rat liver was proportional to O 4 -ethyldeoxythymidine formation in DNA, which was generally proportional to NDEA dose. At low doses in the 0.033–1.1 ppm range, the doseresponse for esophageal tumor formation was sublinear, possibly due to DNA repair. Although no epidemiological studies have specifically evaluated NDEA, sufficient exposure levels would be expected to cause cancer in humans.
Minna Torniainenholm - One of the best experts on this subject based on the ideXlab platform.
-
the nde1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microrna 484
Open Biology, 2017Co-Authors: Nicholas J. Bradshaw, Maiju Pankakoski, Liisa Ukkolavuoti, Amanda B Zheutlin, Alfredo Ortegaalonso, Minna TorniainenholmAbstract:Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the 'DISC1 network'. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p = 3.0 × 10-8), located on a non-coding exon of NDE1 Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.
-
the nde1 genomic locus affects treatment of psychiatric illness through gene expression changes related to microrna 484
bioRxiv, 2016Co-Authors: Nicholas J. Bradshaw, Maiju Pankakoski, Liisa Ukkolavuoti, Amanda B Zheutlin, Alfredo Ortegaalonso, Minna Torniainenholm, Vishal Sinha, Sebastian Therman, Tiina Paunio, Jaana SuvisaariAbstract:Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the DISC1 network. Here, we utilize gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, whilst prescription medication information has been collected over a ten-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2,908 probes (2,542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p=3.0 × 10-8), located on a non-coding exon of NDE1. Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.
Nicholas J. Bradshaw - One of the best experts on this subject based on the ideXlab platform.
-
the nde1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microrna 484
Open Biology, 2017Co-Authors: Nicholas J. Bradshaw, Maiju Pankakoski, Liisa Ukkolavuoti, Amanda B Zheutlin, Alfredo Ortegaalonso, Minna TorniainenholmAbstract:Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the 'DISC1 network'. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p = 3.0 × 10-8), located on a non-coding exon of NDE1 Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.
-
the nde1 genomic locus affects treatment of psychiatric illness through gene expression changes related to microrna 484
bioRxiv, 2016Co-Authors: Nicholas J. Bradshaw, Maiju Pankakoski, Liisa Ukkolavuoti, Amanda B Zheutlin, Alfredo Ortegaalonso, Minna Torniainenholm, Vishal Sinha, Sebastian Therman, Tiina Paunio, Jaana SuvisaariAbstract:Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the DISC1 network. Here, we utilize gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, whilst prescription medication information has been collected over a ten-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2,908 probes (2,542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p=3.0 × 10-8), located on a non-coding exon of NDE1. Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.
-
pka phosphorylation of nde1 is disc1 pde4 dependent and modulates its interaction with lis1 and ndel1
The Journal of Neuroscience, 2011Co-Authors: Nicholas J. Bradshaw, Dinesh C. Soares, Becky C. Carlyle, Fumiaki Ogawa, Sheila Christie, Shaun Mackie, Pippa A. Thomson, David J. Porteous, Hazel Davidsonsmith, Kirsty J MillarAbstract:Nuclear distribution factor E-homolog 1 (NDE1), Lissencephaly 1 (LIS1), and NDE-like 1 (NDEL1) together participate in essential neurodevelopmental processes, including neuronal precursor proliferation and differentiation, neuronal migration, and neurite outgrowth. NDE1/LIS1/NDEL1 interacts with Disrupted in Schizophrenia 1 (DISC1) and the cAMP-hydrolyzing enzyme phosphodiesterase 4 (PDE4). DISC1, PDE4, NDE1, and NDEL1 have each been implicated as genetic risk factors for major mental illness. Here, we demonstrate that DISC1 and PDE4 modulate NDE1 phosphorylation by cAMP-dependent protein kinase A (PKA) and identify a novel PKA substrate site on NDE1 at threonine-131 (T131). Homology modeling predicts that phosphorylation at T131 modulates NDE1–LIS1 and NDE1–NDEL1 interactions, which we confirm experimentally. DISC1–PDE4 interaction thus modulates organization of the NDE1/NDEL1/LIS1 complex. T131-phosphorylated NDE1 is present at the postsynaptic density, in proximal axons, within the nucleus, and at the centrosome where it becomes substantially enriched during mitosis. Mutation of the NDE1 T131 site to mimic PKA phosphorylation inhibits neurite outgrowth. Thus PKA-dependent phosphorylation of the NDE1/LIS1/NDEL1 complex is DISC1–PDE4 modulated and likely to regulate its neural functions.
-
DISC1, PDE4B, and NDE1 at the centrosome and synapse
Biochemical and biophysical research communications, 2008Co-Authors: Nicholas J. Bradshaw, Becky C. Carlyle, Fumiaki Ogawa, Sheila Christie, David J. Porteous, Beatriz Antolin-fontes, Jennifer E. Chubb, Antoine Claessens, J. Kirsty MillarAbstract:Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously suggested to be synaptic, and we now demonstrate localisation of DISC1, NDE1, and PDE4B at synapses in cultured neurons. NDE1 is phosphorylated by cAMP-dependant Protein Kinase A (PKA), whose activity is, in turn, regulated by the cAMP hydrolysis activity of phosphodiesterases, including PDE4. We propose that DISC1 acts as an assembly scaffold for all of these proteins and that the NDE1/NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4.
Andres M Kanner - One of the best experts on this subject based on the ideXlab platform.
-
screening of major depression in epilepsy the neurologic depression disorders inventory in epilepsy spanish version argentina
Epilepsia, 2014Co-Authors: Alfredo Thomson, Analia Calle, Maria Elena Fontela, Luis Yepez, Francisco Munoz Giacomelli, Agustin Jauregui, Juan M Racosta, Andres M KannerAbstract:Summary Objectives To validate and translate the English version of the Neurologic Depression Disorders Inventory in Epilepsy (NDDI-E) into Spanish as a screening instrument for major depressive episodes (MDE) for patients with epilepsy from Argentina and Uruguay. Methods One hundred fifty-five consecutive outpatients with epilepsy participated in this study. The module of MDE of the MINI International Neuropsychiatric Instrument (MINI Plus version) was used as the gold standard against which the translated version of the NDDI-E was validated. Results Among the 155 patients, 25 (16%) met Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) criteria for MDE according to the MINI. With a total score of >15, The NDDI-E identified MDE with an 80% sensitivity, 90% specificity, 60% positive predictive value, and 95.5% negative predictive value. Significance These data indicate that the Spanish version of the NDDI-E can reliably identify MDE in patients with epilepsy from Argentina and Uruguay.
-
screening for major depressive episodes in japanese patients with epilepsy validation and translation of the japanese version of neurological disorders depression inventory for epilepsy nddi e
Epilepsy & Behavior, 2012Co-Authors: Yukari Tadokoro, Andres M Kanner, Tomohiro Oshima, Toshihiko Fukuchi, Kousuke KanemotoAbstract:We validated and translated into Japanese the English version of the screening instrument Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) to identify major depressive episodes in patients with epilepsy. A total of 159 Japanese subjects with epilepsy underwent a psychiatric structured interview with the Japanese version of the Mini International Neuropsychiatric Interview (M.I.N.I.-J) followed by completion of the Japanese version of NDDI-E (NDDI-E-J). Twelve participants met the M.I.N.I.-J criteria of current major depressive episode. Participants had no difficulties completing the NDDI-E-J. Its Cronbach's alpha coefficient was 0.83 and a cut-off score greater than 16 provided a sensitivity of 0.92, a specificity of 0.89, and a negative predictive value of 0.99. The NDDI-E-J appears to be useful for primary care clinicians to screen for major depressive episodes in epilepsy patients. Routine use of this brief and self-administered instrument in busy clinical settings will likely improve management of depression in Japanese individuals with epilepsy.
-
brazilian version of the neurological disorders depression inventory for epilepsy nddi e
Epilepsy & Behavior, 2010Co-Authors: Guilherme Nogueira M De Oliveira, Arthur Kummer, Joao Vinicius Salgado, Eduardo Jardel Portela, Silvio Roberto Sousapereira, Anthony S David, Andres M Kanner, Antonio Lucio TeixeiraAbstract:Abstract Objective The purpose of this research was to evaluate the Brazilian-Portuguese version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and to assess its psychometric properties. Methods This study involved 98 outpatients who underwent psychopathological evaluation with the Mini International Neuropsychiatric Interview—Plus Version, Hamilton Depression Scale (HAM-D), and a Portuguese version of the NDDI-E. Results The NDDI-E was easily understood and quickly administered to most of the patients. At a cutoff score > 15, NDDI-E had a sensitivity of 81.5%, a specificity of 83.1%, and a negative predictive value of 92.2% for diagnosis of major depression. Internal consistency reliability of the NDDI-E was 0.79, and there was also a positive correlation between the NDDI-E and the HAM-D (P Conclusion The Brazilian-Portuguese version of NDDI-E can be used as a practical screening tool to improve recognition of depression in Brazilian people with epilepsy.
