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1.
Front Mol Neurosci ; 16: 1133218, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873103

RESUMO

To better understand zinc and copper regulation and their involvement in various biochemical pathways as it relates to autism spectrum disorder (ASD), isotopic composition of serum zinc and copper were evaluated in both healthy children and children with ASD in North America. No significant difference in isotopic composition of serum zinc or copper with respect to healthy controls and ASD children were identified. However, the isotopic composition of serum copper in boys was found to be enriched in 65Cu in comparison to previously published healthy adult copper isotopic composition. Furthermore, in both boys and girls, the average isotopic composition of serum zinc is heavier than previously published healthy adult isotopic zinc composition. There was also a negative association between total zinc concentrations in serum and the zinc isotopic composition of serum in boys. Finally, children with heavier isotopic composition of copper also showed a high degree of variability in their zinc isotopic composition. While numerous studies have measured the isotopic composition of serum zinc and copper in adults, this is one of the first studies which measured the isotopic composition of serum copper and zinc in children, specifically those diagnosed with ASD. The results of this study showed that age and gender specific normal ranges of isotopic composition must be established to effectively use isotopic composition analysis in studying various diseases including ASD.

2.
Phys Rev Lett ; 127(11): 112501, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34558921

RESUMO

High-accuracy mass measurements of neutron-deficient Yb isotopes have been performed at TRIUMF using TITAN's multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS). For the first time, an MR-TOF-MS was used on line simultaneously as an isobar separator and as a mass spectrometer, extending the measurements to two isotopes further away from stability than otherwise possible. The ground state masses of ^{150,153}Yb and the excitation energy of ^{151}Yb^{m} were measured for the first time. As a result, the persistence of the N=82 shell with almost unmodified shell gap energies is established up to the proton drip line. Furthermore, the puzzling systematics of the h_{11/2}-excited isomeric states of the N=81 isotones are unraveled using state-of-the-art mean field calculations.

3.
Proc Natl Acad Sci U S A ; 116(13): 5955-5960, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30850515

RESUMO

Copper is a critical enzyme cofactor in the body but also a potent cellular toxin when intracellularly unbound. Thus, there is a delicate balance of intracellular copper, maintained by a series of complex interactions between the metal and specific copper transport and binding proteins. The gastrointestinal (GI) tract is the primary site of copper entry into the body and there has been considerable progress in understanding the intricacies of copper metabolism in this region. The GI tract is also host to diverse bacterial populations, and their role in copper metabolism is not well understood. In this study, we compared the isotopic fractionation of copper in the GI tract of mice with intestinal microbiota significantly depleted by antibiotic treatment to that in mice not receiving such treatment. We demonstrated variability in copper isotopic composition along the length of the gut. A significant difference, ∼1.0‰, in copper isotope abundances was measured in the proximal colon of antibiotic-treated mice. The changes in copper isotopic composition in the colon are accompanied by changes in copper transporters. Both CTR1, a copper importer, and ATP7A, a copper transporter across membranes, were significantly down-regulated in the colon of antibiotic-treated mice. This study demonstrated that isotope abundance measurements of metals can be used as an indicator of changes in metabolic processes in vivo. These measurements revealed a host-microbial interaction in the GI tract involved in the regulation of copper transport.


Assuntos
Antibacterianos/farmacologia , Colo/efeitos dos fármacos , Cobre/metabolismo , Animais , Proteínas de Transporte de Cátions/metabolismo , Colo/química , Colo/metabolismo , Cobre/análise , Transportador de Cobre 1 , ATPases Transportadoras de Cobre/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Isótopos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Superóxido Dismutase-1/metabolismo
4.
Metallomics ; 9(12): 1809-1819, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29139524

RESUMO

Changes in the stable isotope composition of copper in blood serum as a result of biological processes in the liver were quantified as coupled equilibrium fractionation processes. The model used calculated reduced partition function ratios corresponding to interactions involving individual proteins using Density Functional Theory. This quantified the effect that each process had on the redistribution of copper isotopes in the liver. It was not possible to calculate the reduced partition function of CTR1 as a high resolution crystal structure of its copper binding domains are unavailable at the time of writing, and an optimization process was used to estimate the reduced partition function of CTR1 and constrain the possible isotopic fractionation associated with interactions involving CTR1 independent of direct DFT calculations and assumptions of its structure. The exchange of copper between ceruloplasmin and ATP7B has the most significant impact on the copper isotopic composition of blood serum. The model calculation for the isotopic composition of ceruloplasmin and albumin are δ65Cu = (-0.54 ± 0.10)‰ and δ65Cu = (0.08 ± 0.25)‰ respectively, assuming that serum is 90% ceruloplasmin and 10% albumin using a measured δ65Cu of serum of (0.52 ± 0.08)‰. The model also predicts that the isotopic composition of the tri-nuclear binding motif of ceruloplasmin may be relatively depleted in the lighter isotope of Cu compared to the other copper binding sites by as much as -1.08 ± 0.45‰.


Assuntos
Ceruloplasmina/metabolismo , Simulação por Computador , Radioisótopos de Cobre/sangue , Fígado/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Transportador de Cobre 1 , Humanos
5.
Anal Bioanal Chem ; 405(9): 2957-63, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23338755

RESUMO

Here, we report the first measurements of the molybdenum (Mo) isotopic composition of aerosols collected on Teflon air filters. Mo concentrations and isotopic compositions were measured at selected locations in the city of Calgary, Canada, including a residence, the isotope laboratory at the University of Calgary, the University of Calgary weather station, and the City of Calgary Transit bus garage. Concentrations ranged from 0.07 ng/m(3) in the laboratory to 19.0 ng/m(3) in the bus garage. The concentrations of Mo in the air samples collected in the bus garage were the highest measured in this study. To date, there are no reported data for the Mo isotopic composition of airborne Mo. In this study, the δ(98/95)Mo values measured for the different urban sampling sites and reported relative to SRM 3134, ranged from -0.18 to +0.94 ‰. The results of this investigation suggest that measurements of Mo concentrations and isotopic compositions have the potential to trace anthropogenic emissions in an urban environment.

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