scholarly journals A Method for Investigation of Size-Dependent Protein Binding to Nanoholes Using Intrinsic Fluorescence of Proteins

ACS Omega ◽  
2017 ◽  
Vol 2 (8) ◽  
pp. 4772-4778 ◽  
Author(s):  
Bita Malekian ◽  
Ivan Maximov ◽  
Rainer Timm ◽  
Tommy Cedervall ◽  
Dan Hessman
Keyword(s):  
Protein Binding ◽  
Intrinsic Fluorescence ◽  
Size Dependent ◽  
Dependent Protein

scholarly journals Single-Nucleotide Polymorphisms Sequencing Identifies Candidate Functional Variants at Prostate Cancer Risk Loci

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 547 ◽  
Author(s):  
Peng Zhang ◽  
Lori S. Tillmans ◽  
Stephen N. Thibodeau ◽  
Liang Wang
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Single Nucleotide Polymorphisms ◽  
Protein Binding ◽  
Prostate Cancer Risk ◽  
Sequencing Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Functional Variants ◽  
Dependent Protein

Genome-wide association studies have identified over 150 risk loci that increase prostate cancer risk. However, few causal variants and their regulatory mechanisms have been characterized. In this study, we utilized our previously developed single-nucleotide polymorphisms sequencing (SNPs-seq) technology to test allele-dependent protein binding at 903 SNP sites covering 28 genomic regions. All selected SNPs have shown significant cis-association with at least one nearby gene. After preparing nuclear extract using LNCaP cell line, we first mixed the extract with dsDNA oligo pool for protein–DNA binding incubation. We then performed sequencing analysis on protein-bound oligos. SNPs-seq analysis showed protein-binding differences (>1.5-fold) between reference and variant alleles in 380 (42%) of 903 SNPs with androgen treatment and 403 (45%) of 903 SNPs without treatment. From these significant SNPs, we performed a database search and further narrowed down to 74 promising SNPs. To validate this initial finding, we performed electrophoretic mobility shift assay in two SNPs (rs12246440 and rs7077275) at CTBP2 locus and one SNP (rs113082846) at NCOA4 locus. This analysis showed that all three SNPs demonstrated allele-dependent protein-binding differences that were consistent with the SNPs-seq. Finally, clinical association analysis of the two candidate genes showed that CTBP2 was upregulated, while NCOA4 was downregulated in prostate cancer (p < 0.02). Lower expression of CTBP2 was associated with poor recurrence-free survival in prostate cancer. Utilizing our experimental data along with bioinformatic tools provides a strategy for identifying candidate functional elements at prostate cancer susceptibility loci to help guide subsequent laboratory studies.

scholarly journals Size-dependent protein segregation at membrane interfaces

2016 ◽  
Vol 12 (7) ◽  
pp. 704-711 ◽  
Author(s):  
Eva M. Schmid ◽  
Matthew H. Bakalar ◽  
Kaushik Choudhuri ◽  
Julian Weichsel ◽  
Hyoung Sook Ann ◽  
...  
Keyword(s):  
Size Dependent ◽  
Membrane Interfaces ◽  
Dependent Protein

Apparent Valproic Acid Neurotoxicity in a Hypoalbuminemic Patient

1993 ◽  
Vol 27 (1) ◽  
pp. 32-35 ◽  
Author(s):  
Barry E. Gidal ◽  
D. Michael Collins ◽  
Brad R. Beinlich
Keyword(s):  
Valproic Acid ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Plasma Concentrations ◽  
Free Fraction ◽  
Laboratory Evaluation ◽  
Neurologic Symptoms ◽  
Drug Concentrations ◽  
Dependent Protein

OBJECTIVE: To report a case of possible neurotoxicity caused by markedly elevated free valproic acid (VPA) plasma concentrations. CASE SUMMARY: A patient with a history of a mixed-type seizure disorder that had been treated with oral VPA 1000 mg four times daily for the previous two years was admitted to the neurology service with the chief complaint of increasing difficulty in walking and involuntary muscle jerks that were new in onset. The patient was hypersomnolent and dysarthric. The total plasma VPA concentration was 103 μg/mL, which was only slightly above the recommended therapeutic range (50–100 μg/mL). VPA free fraction and free plasma concentrations, however, were unexpectedly elevated (26 percent, 26.8 μg/mL, respectively). Further laboratory evaluation revealed a serum albumin concentration of 33 g/L. The neurologic symptoms resolved upon VPA dosage reduction. DISCUSSION: VPA displays concentration-dependent protein binding, resulting in disproportionate increases in drug free fraction with increasing drug concentration. This effect may be magnified in patients with decreased plasma protein-binding capacity. The plasma protein-binding kinetics of VPA are reviewed and the implications for therapeutic drug monitoring are discussed. CONCLUSIONS: It is likely that the markedly elevated free VPA plasma concentrations contributed to the neurologic symptoms displayed in this patient. In patients with decreased albumin concentrations, failure to recognize concentration-dependent protein binding, as well as exclusive reliance upon total drug concentrations, may lead to erroneous pharmacokinetic and therapeutic interpretations.

scholarly journals Microscopic Investigation of Reversible Nanoscale Surface Size Dependent Protein Conjugation

2009 ◽  
Vol 10 (5) ◽  
pp. 2348-2366 ◽  
Author(s):  
Kazushige Yokoyama ◽  
Hyunah Cho ◽  
Sean Cullen ◽  
Matthew Kowalik ◽  
Nicole Briglio ◽  
...  
Keyword(s):  
Microscopic Investigation ◽  
Protein Conjugation ◽  
Size Dependent ◽  
Dependent Protein

Phenobarbital-dependent protein binding to Barbie box-like sequences in the coding region of cytochrome P450BM-3 gene from Bacillus megaterium

Gene ◽  
1996 ◽  
Vol 183 (1-2) ◽  
pp. 97-101 ◽  
Author(s):  
Elena K. Gaidamakova ◽  
Oleg V. Alpatov ◽  
Igor V. Ischenko ◽  
Sergei P. Kovalenko ◽  
Vyacheslav V. Lyakhovich
Keyword(s):  
Protein Binding ◽  
Bacillus Megaterium ◽  
Coding Region ◽  
Dependent Protein
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