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Low serum zinc is associated with elevated risk of cadmium nephrotoxicity.

Low serum zinc is associated with elevated risk of cadmium nephrotoxicity.

Environ Res. 2014 Jul 17;134C:33-38

Authors: Lin YS, Ho WC, Caffrey JL, Sonawane B

Abstract
BACKGROUND: Despite animal evidence suggests that zinc modulates cadmium nephrotoxicity, limited human data are available.
OBJECTIVE: To test the hypothesis that low serum zinc concentrations may increase the risk of cadmium-mediated renal dysfunction in humans.
METHODS: Data from 1545 subjects aged 20 or older in the National Health and Nutrition Examination Survey (NHANES), 2011-2012 were analyzed. Renal function was defined as impaired when estimated glomerular filtration rate (eGFR) fell below 60ml/min/1.73m(2) and/or the urinary albumin-to-creatinine ratio surpassed 2.5 in men and 3.5mg/mmol in women.
RESULTS: Within the study cohort, 117 subjects had reduced eGFR and 214 had elevated urinary albumin. After adjusting for potential confounders, subjects with elevated blood cadmium (>0.53μg/L) were more likely to have a reduced eGFR (odds ratio [OR]=2.21, 95% confidence interval [CI]: 1.09-4.50) and a higher urinary albumin (OR=2.04, 95% CI: 1.13-3.69) than their low cadmium (<0.18μg/L) peers. In addition, for any given cadmium exposure, low serum zinc is associated with elevated risk of reduced eGFR (OR=3.38, 95% CI: 1.39-8.28). A similar increase in the odds ratio was observed between declining serum zinc and albuminuria but failed to reach statistical significance. Those with lower serum zinc/blood cadmium ratios were likewise at a greater risk of renal dysfunction (p<0.01).
CONCLUSIONS: This study results suggest that low serum zinc concentrations are associated with an increased risk of cadmium nephrotoxicity. Elevated cadmium exposure is global public health issue and the assessment of zinc nutritional status may be an important covariate in determining its effective renal toxicity.

PMID: 25042034 [PubMed - as supplied by publisher]

Characterization of [(3) H]LS-3-134, a Novel Arylamide Phenylpiperazine D3 Dopamine Receptor Selective Radioligand.

Characterization of [(3) H]LS-3-134, a Novel Arylamide Phenylpiperazine D3 Dopamine Receptor Selective Radioligand.

J Neurochem. 2014 Jul 18;

Authors: Rangel-Barajas C, Malik M, Taylor M, Neve KA, Mach RH, Luedtke RR

Abstract
LS-3-134 is a substituted N-phenylpiperazine derivative that has been reported to exhibit a) high-affinity binding (Ki value 0.2 nM) at human D3 dopamine receptors, b) >100-fold D3 vs. D2 dopamine receptor subtype binding selectivity and c) low-affinity binding (Ki values >5,000 nM) at sigma 1 and sigma 2 receptors. Based upon a forskolin-dependent activation of the adenylyl cyclase inhibition assay, LS-3-134 is a weak partial agonist at both D2 and D3 dopamine receptor subtypes (29% and 35% of full agonist activity, respectively). In this study, [(3) H]-labeled LS-3-134 was prepared and evaluated to further characterize its use as a D3 dopamine receptor selective radioligand. Kinetic and equilibrium radioligand binding studies were performed. This radioligand rapidly reaches equilibrium (10-15 min at 37°C) and binds with high affinity to both human (Kd = 0.06 ± 0.01 nM) and rat (Kd = 0.2 ± 0.02 nM) D3 receptors expressed in HEK-293 cells. Direct and competitive radioligand binding studies using rat caudate and nucleus accumbens tissue indicate that [(3) H]LS-3-134 selectively binds a homogeneous population of binding sites with a dopamine D3 receptor pharmacological profile. Based upon these studies we propose that [(3) H]LS-3-134 represents a novel D3 dopamine receptor selective radioligand that can be used for studying the expression and regulation of the D3 dopamine receptor subtype. This article is protected by copyright. All rights reserved.

PMID: 25041389 [PubMed - as supplied by publisher]

Lenticular mitoprotection. Part B: GSK-3β and regulation of mitochondrial permeability transition for lens epithelial cells in atmospheric oxygen.

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Lenticular mitoprotection. Part B: GSK-3β and regulation of mitochondrial permeability transition for lens epithelial cells in atmospheric oxygen.

Mol Vis. 2013;19:2451-67

Authors: Brooks MM, Neelam S, Cammarata PR

Abstract
PURPOSE: Loss of integrity of either the inner or outer mitochondrial membrane results in the dissipation of the mitochondrial electrochemical gradient that leads to mitochondrial membrane permeability transition (mMPT). This study emphasizes the role of glycogen synthase kinase 3beta (GSK-3β) in maintaining mitochondrial membrane potential, thus preventing mitochondrial depolarization (hereafter termed mitoprotection). Using 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763), an inhibitor of GSK-3β, and drawing a distinction between it and 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (UO126), an inhibitor of extracellular-signal-regulated kinase (ERK) phosphorylation, the means by which GSK-3β influences mitoprotection in cultured human lens epithelial (HLE-B3) cells and normal, secondary cultures of bovine lens epithelial cells, maintained in atmospheric oxygen, was investigated.
METHODS: Virally transfected human lens epithelial cells (HLE-B3) and normal cultures of bovine lens epithelial cells were exposed to acute hypoxic conditions (about 1% O2) followed by exposure to atmospheric oxygen (about 21% O2). Specific antisera and western blot analysis was used to examine the state of phosphorylation of ERK and GSK-3β, as well as the phosphorylation of a downstream substrate of GSK-3β, glycogen synthase (GS, useful in monitoring GSK-3β activity). The potentiometric dye, 1H-benzimidazolium-5,6-dichloro-2-[3-(5,6-dichloro-1,3-diethyl-1,3-dihydro-2H-benzimidazol-2-ylidene)-1-propenyl]-1,3-diethyl-iodide (JC-1), was used to monitor mitochondrial depolarization upon exposure of inhibitor treatment relative to the control cells (mock inhibition) in atmospheric oxygen. Caspase-3 activation was scrutinized to determine whether mitochondrial depolarization inevitably leads to apoptosis.
RESULTS: Treatment of HLE-B3 cells with SB216763 (12 µM) inactivated GSK-3β activity as verified by the enzyme's inability to phosphorylate its substrate, GS. SB216763-treated cells were not depolarized relative to the control cells as demonstrated with JC-1 fluorescent dye analysis. The HLE-B3 cells treated with UO126, which similarly blocked phosphorylation of GS, were nevertheless prone to mMPT relative to the control cells. Western blot analysis determined that Bcl-2-associated X (BAX) levels were unchanged for SB216763-treated or UO126-treated HLE-B3 cells when compared to their respective control cells. However, unlike the SB216763-treated cells, the UO126-treated cells showed a marked absence of Bcl-2, as well as phosphorylated Bcl-2 relative to the controls. UO126 treatment of bovine lens epithelial cells showed similar results with pBcl-2 levels, while the Bcl-2 content appeared unchanged relative to the control cells. HLE-B3 and normal bovine lens cell cultures showed susceptibility to mMPT associated with the loss of pBcl-2 by UO126 treatment.
CONCLUSIONS: MITOCHONDRIAL DEPOLARIZATION MAY OCCUR BY ONE OF TWO KEY OCCURRENCES: interruption of the electrochemical gradient across the inner mitochondrial membrane resulting in mMPT or by disruption of the integrity of the inner or outer mitochondrial membrane. The latter scenario is generally tightly regulated by members of the Bcl-2 family of proteins. Inhibition of GSK-3β activity by SB216763 blocks mMPT by preventing the opening of the mitochondrial permeability transition pore. UO126, likewise, inhibits GSK-3β activity, but unlike SB216763, inhibition of ERK phosphorylation induces the loss of intracellular pBcl-2 levels under conditions where intracellular BAX levels remain constant. These results suggest that the lenticular mitoprotection normally afforded by the inactivation of GSK-3β activity may, however, be bypassed by a loss of pBcl-2, an anti-apoptotic member of the Bcl-2 family. Bcl-2 prevents the translocation of BAX to the mitochondrial outer membrane inhibiting depolarization by disrupting the normal electrochemical gradient leading to mMPT.

PMID: 24319338 [PubMed - indexed for MEDLINE]

Single nucleotide polymorphism typing with massively parallel sequencing for human identification.

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Single nucleotide polymorphism typing with massively parallel sequencing for human identification.

Int J Legal Med. 2013 Nov;127(6):1079-86

Authors: Seo SB, King JL, Warshauer DH, Davis CP, Ge J, Budowle B

Abstract
The Ion AmpliSeq™ HID single nucleotide polymorphism (SNP) panel, a primer pool of 103 autosomal SNPs and 33 Y-SNPs, was evaluated using the Ion 314™ Chip on the Ion PGM™ Sequencer with four DNA samples. The study focused on the sequencing of DNA at three different initial target quantities, related interpretation issues, and concordance of results with another sequencing platform, i.e., Genome Analyzer IIx. With 10 ng of template DNA, all genotypes at the 136 SNPs were detected. With 1 ng of DNA, all SNPs were detected and one SNP locus in one sample showed extreme heterozygote imbalance on allele coverage. With 100 pg of DNA, an average of 1.6 SNP loci were not detected, and an average of 4.3 SNPs showed heterozygote imbalance. The average sequence coverage was 945-600× at autosomal SNPs and 465-209× at Y-SNPs for 10 ng-100 pg of DNA. The average heterozygote allele coverage ratio was 89.6-61.8 % for 10 ng-100 pg of DNA. At 10 ng of DNA, all genotypes of the 95 SNPs shared between the two different sequencing platforms were concordant except for one SNP, rs1029047. The error was due to the misalignment of a flanking homopolymer. Overall, the data support that genotyping a large battery of SNPs is feasible with massively parallel sequencing. With barcode systems, better allele balance, and specifically designed alignment software, a more comprehensive rapid genotyping and more cost-effective results may be obtained from multiple samples in one analysis than are possible with current typing and capillary electrophoresis systems.

PMID: 23736940 [PubMed - indexed for MEDLINE]

PTEN degradation after ischemic stroke: A double-edged sword

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Author(s):Li, W. | Huang, R. | Chen, Z. | Yan, L.-J. | Simpkins, J.W. | Yang, S.-H.
Publication year: 2014
Journal / Book title: Neuroscience

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ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning

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Author(s):Su, C. | Sun, F. | Cunningham, R.L. | Rybalchenko, N. | Singh, M.
Publication year: 2014
Journal / Book title: AGE

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The Association between Patient-Centered Attributes of Care and Patient Satisfaction

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Author(s):Tak, H. | Ruhnke, G.W. | Shih, Y.-C.T.
Publication year: 2014
Journal / Book title: The Patient - Patient-Centered Outcomes Research

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Evidence of brain tumor stem progenitor-like cells with low proliferative capacity in human benign pituitary adenoma

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Author(s):Chen, L. | Ye, H. | Wang, X. | Tang, X. | Mao, Y. | Zhao, Y. | Wu, Z. | Mao, X.O. | Xie, L. | Jin, K. | Yao, Y.
Publication year: 2014
Journal / Book title: Cancer Letters

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Total Cholesterol and Neuropsychiatric Symptoms in Alzheimer's Disease: The Impact of Total Cholesterol Level and Gender

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Author(s):Hall, J.R. | Wiechmann, A.R. | Johnson, L.A. | Edwards, M. | Barber, R.C. | Cunningham, R. | Singh, M. | O'Bryant, S.E.
Publication year: 2014
Journal / Book title: Dementia and Geriatric Cognitive Disorders

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The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice

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Author(s):Carbonaro, T.M. | Eshleman, A.J. | Forster, M.J. | Cheng, K. | Rice, K.C. | Gatch, M.B.
Publication year: 2014
Journal / Book title: Psychopharmacology

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Projection target-specific action of nicotine in the caudal nucleus of the solitary tract

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Author(s):Feng, L. | Uteshev, V.V.
Publication year: 2014
Journal / Book title: Journal of Neuroscience Research

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Identification and characterization of the spiruchostatin biosynthetic gene cluster enable yield improvement by overexpressing a transcriptional activator

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Author(s):Potharla, V.Y. | Wang, C. | Cheng, Y.-Q.
Publication year: 2014
Journal / Book title: Journal of Industrial Microbiology & Biotechnology

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Clinical response and relapse in patients with chronic low back pain following osteopathic manual treatment: Results from the OSTEOPATHIC Trial

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Author(s):Licciardone, J.C. | Aryal, S.
Publication year: 2014
Journal / Book title: Manual Therapy

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Role of deuterium desorption kinetics on the thermionic emission properties of polycrystalline diamond films with respect to kinetic isotope effects

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Author(s):Paxton, W.F. | Brooks, M.M. | Howell, M. | Tolk, N. | Kang, W.P. | Davidson, J.L.
Publication year: 2014
Journal / Book title: Journal of Applied Physics

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Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus

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Author(s):Chen, Z.-L. | Huang, R.-Q.
Publication year: 2014
Journal / Book title: Neuroscience

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Enhanced toxicity of cisplatin with chemosensitizer phenethyl isothiocyanate toward non-small cell lung cancer cells when delivered in liposomal nanoparticles

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Author(s):Yang, Y.-T. | Shi, Y. | Jay, M. | Di Pasqua, A.J.
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Journal / Book title: Chemical Research in Toxicology

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Autonomic neural control of heart rate during dynamic exercise: Revisited

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Author(s):White, D.W. | Raven, P.B.
Publication year: 2014
Journal / Book title: Journal of Physiology

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MTOR Signaling inhibition modulates macrophage/microglia-mediated neuroinflammation and secondary injury via regulatory T cells after focal ischemia

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Author(s):Xie, L. | Sun, F. | Wang, J. | Mao, X.O. | Xie, L. | Yang, S.-H. | Su, D.-M. | Simpkins, J.W. | Greenberg, D.A. | Jin, K.
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Journal / Book title: Journal of Immunology

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HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through conduits and enhances HCV replication

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Author(s):Park, I.-W. | Fan, Y. | Luo, X. | Ryou, M.-G. | Liu, J. | Green, L. | He, J.J.
Publication year: 2014
Journal / Book title: PLoS ONE

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Associations of health disparities and physical activity with children's health and academic problems

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Author(s):Shi, X. | Tubb, L. | Chen, S. | Fulda, K.G. | Franks, S. | Reeves, R. | Lister, G.
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Journal / Book title: Journal of Exercise Science and Fitness

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