A5088549451- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Genomics and Chromatin Dynamics
- Genetic Neurodegenerative Diseases
- Advanced biosensing and bioanalysis techniques
- Metal complexes synthesis and properties
- Epigenetics and DNA Methylation
- Forensic Toxicology and Drug Analysis
- RNA and protein synthesis mechanisms
- Opioid Use Disorder Treatment
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Ferrocene Chemistry and Applications
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Poisoning and overdose treatments
- Cannabis and Cannabinoid Research
- Pharmacological Effects and Toxicity Studies
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Lipoproteins and Cardiovascular Health
- Breastfeeding Practices and Influences
- Maternal Mental Health During Pregnancy and Postpartum
- Anorectal Disease Treatments and Outcomes
- Infant Health and Development
University of Toronto
2010-2024
St. Michael's Hospital
2021-2024
Brown University
2015-2024
Unity Health Toronto
2021-2024
Ollscoil na Gaillimhe – University of Galway
2022
Mayo Clinic in Arizona
2020-2021
WinnMed
2019
Hospital for Sick Children
2012-2018
Dabur (India)
2015
Sappasithiprasong Hospital
2015
A series of PtIV anticancer complexes with chloro leaving groups have been investigated for the effects axial and carrier ligands on reduction cytotoxicity. The rates such as Pt(d,l)(1,2-(NH2)2C6H10)Cl4 (tetraplatin, Pt(dach)Cl4; dach = diaminocyclohexane), cis,trans,cis-[Pt((CH3)2CHNH2)2(OH)2Cl2] (iproplatin, Pt(ipa)(OH)2Cl2; ipa isopropylamine), cis,trans,cis-[Pt(NH3)(C6H11NH2)(OCOCH3)2Cl2] (JM-216, Pt(a,cha)(OCOCH3)2Cl2; a ammine, cha cyclohexylamine),...
Interactions with DNA by a family of ruthenium(II) complexes bearing the dppz (dppz = dipyridophenazine) ligand or its derivatives have been examined. The include Ru(bpy)2(dppx)2+ (dppx 7,8-dimethyldipyridophenazine), Ru(bpy)2(dpq)2+ (dpq dipyridoquinoxaline), and Ru(bpy)2(dpqC)2+ (dpqC dipyrido-6,7,8,9-tetrahydrophenazine). Their ground excited state oxidation/reduction potentials determined using cyclic voltammetry fluorescence spectroscopy. An intercalative binding mode has established on...
ConspectusOur cellular genome is continuously exposed to a wide spectrum of exogenous and endogenous DNA damaging agents. These agents can lead formation an extensive array lesions including single- double-stranded breaks, inter- intrastrand cross-links, abasic sites, modification nucleobases. Persistence these be both mutagenic cytotoxic, cause altered gene expression apoptosis leading aging, cancer, various neurological disorders. To combat the deleterious effects lesions, cells have...
Abstract Background The North American opioid overdose crisis is driven in large part by the presence of unknown psychoactive adulterants dynamic, unregulated drug supply. We herein report first detection veterinary compound xylazine Toronto, largest urban center Canada, city’s checking service. Methods Toronto’s Drug Checking Service launched October 2019. Between then and February 2021, 2263 samples were submitted for analysis. service offered voluntarily at harm reduction agencies that...
Damage to genomic DNA leads mutagenesis and disease. Repair of single base damage is initiated by glycosylases, the first enzymes in excision repair pathway. Although eukaryotic packaging chromosomal nucleosomes known decrease glycosylase efficiency, impact on individual glycosylases unclear. Here, we present a model system which examine site-specific well-characterized nucleosome core particles five different glycosylases. We find that efficiency substrates depends not only geometric...
Triplet repeat sequences, such as CAG/CTG, expand in the human genome to cause several neurological disorders. As part of expansion process formation non-B DNA conformations by sequence has previously been proposed. Furthermore, base excision repair enzyme 7,8-dihydro-8-oxoguanine glycosylase (OGG1) recently implicated [Kovtun, I. V., Liu, Y., Bjoras, M., Klugland, A., Wilson, S. H., and McMurray, C. T. (2007) Nature 447, 447−452]. In this work we have found that conformation adopted...
Reactive oxygen and nitrogen radicals produced during metabolic processes, such as respiration inflammation, combine with DNA to form many lesions primarily at guanine sites. Understanding the roles of polymerases responsible for processing these products mutations could illuminate molecular mechanisms that correlate oxidative stress cancer. Using M13 viral genomes engineered contain single Escherichia coli strains specific polymerase (pol) knockouts, we show pol V is required efficient...
Apurinic/apyrimidinic endonuclease 1 (APE1) is an Mg²⁺-dependent enzyme responsible for incising the DNA backbone 5' to apurinic/apyrimidinic (AP) site. Here, we use rapid quench flow (RQF) techniques provide a comprehensive kinetic analysis of strand-incision activity (k(chemistry)) APE1 acting on authentic AP site along with two widely used analogs, reduced and tetrahydrofuran (THF) In presence biologically relevant Mg²⁺, incises all three substrates at rate faster than resolution RQF,...
Persistent DNA damage is responsible for mutagenesis, aging, and disease. Repair of the prototypic oxidatively damaged guanine lesion 8-oxo-7,8-dihydroguanine (8-oxoG) initiated by oxoguanine glycosylase (hOGG1 in humans). In this work, we examine hOGG1 activity on packaged as it chromatin, a nucleosome core particle (NCP). We use synthetic methods to generate population NCPs with G 8-oxoG substitutions evaluate global profile repair DNA. For several turns helix, observe that solution...
DNA conjugates containing adjacent duplex and guanine quadruplex assemblies have been designed to explore charge transport into architectures. The characterized structurally using circular dichroism by assaying for chemical protection. Using an intercalating rhodium photooxidant, noncovalently bound or tethered the end, oxidizing radicals are found be trapped in folded quadruplex. Damage is observed almost exclusively at external tetrads of Little damage center tetrad observed, due most...
The DNA damage product 7,8-dihydro-8-oxo-2'-deoxyguanine (8-oxoG) is a commonly used biomarker of oxidative stress. mutagenic potential this lesion mitigated in Escherichia coli by multiple enzymes. One these enzymes, MutY, excises an A mispaired with 8-oxoG as part the process to restore original G:C base pair. However, numerous studies have shown that chemically labile toward further oxidation. Here, we examine activity MutY on oxidation products guanidinohydantoin (Gh), two diastereomers...
This study investigated the effectiveness of orally delivered sucrose in calming agitated 2- and 4-week-old infants. Sucrose arrested crying reduced heart rate gross activity 2-week-olds but was ineffective 4-week-olds unless accompanied by eye contact. These results were confirmed a second which experimenter deliberately either held or avoided infants' gaze. For infants who received absence contact, water along with only modestly reduced, this effect not sustained. The emergent necessity...