The prevalence of DHEAS excess is approximately 20% among White and 30% among Black PCOS patients, when using age- and race-adjusted normative values. This study also indicates that the age-associated decline in DHEAS levels is observable and similar in both control and PCOS women, regardless of race. While BMI and fasting insulin had little impact on circulating DHEAS levels in healthy women, among White PCOS patients these parameters were negatively associated with circulating DHEAS levels.
Eumenorrheic, nonhirsute Black women have a lower range of normal androgen levels than White women of the same age, BMI, WHR, and homeostasis model assessment index for insulin resistance. Race and age-adjusted data should be considered when evaluating androgen levels in women between the ages of 15 and 60 yr.
Patients suffering from familial Parkinson’s disease are linked to mutated DJ-1 protein. Wild-type DJ-1 occurs as a homodimer, which appears to be crucial for its function. It has been established that mutation (L166P) in DJ-1 protein could destabilize the DJ-1 homodimer. Hence, dimerization aspect of DJ-1 is fundamentally important for understanding its link to the disease. X-ray structures of wild-type DJ-1 dimer have given an atomic insight into the interaction network at the dimer interface. However, the energetics of dimerization in the wild-type and its mutant protein is unknown. Using the X-ray structure of wild-type DJ-1 as the template, we report ∼1.55 μs of molecular dynamics simulations to quantitatively estimate the relative free energy of DJ-1 dimerization in the disease linked variant (L166P, A104T, and M26I) with respect to its wild-type analogue. The results suggest that dimerization is disfavored for L166P and A104T mutations, severely for the former. Notably, the M26I mutation does not alter the energetics of DJ-1 dimerization. The dynamics of the DJ-1 dimer is significantly altered in response to the L166P and A104T mutations, resulting in the significant loss of interactions at the dimer interface. L166P mutant showed the structural difference and increased flexibility in α6, α7, α8 regions with respect to the WT. A structural difference in the α6 region was noticeable between WT and A104T mutant of DJ-1. The interaction network in the dimer interface is identical for the wild-type protein and the M26I mutant. No significant change in secondary structural content was observed for DJ-1 mutants (L166P, A104T, M26I) with respect to its WT analogue.
CRISPR-associated protein 1 (Cas1) is a universally conserved essential metalloenzyme of the clustered regularly interspaced short palindromic repeat (CRISPR) immune system of prokaryotes (bacteria, archaea) that can cut and integrate a part of viral DNA to its host genome with the help of other proteins. The integrated DNA acts as a memory of viral infection, which can be transcribed to RNA and stop future infection by recognition (based on the RNA/DNA complementarity principle) followed by protein-mediated degradation of the viral DNA. It has been proposed that the presence of a single manganese (Mn2+) ion in a conserved divalent-metal-ion binding pocket (key residues: E190, H254, D265, D268) of Cas1 is crucial for its function. Cas1-mediated DNA degradation was proposed to be hindered by metal substitution, metal chelation, or mutation of the binding pocket residues. Cas1 is active toward dsDNA degradation with both Mn2+ and Mg2+. X-ray structures of Cas1 revealed an intricate atomic interaction network of the divalent-metal-ion binding pocket and opened up the possibility of modeling related metal ions (viz., Mg2+, Ca2+) in the binding pocket of wild-type (WT) and mutated Cas1 proteins for computational analysis, which includes (1) quantitative estimation of the energetics of the divalent-metal-ion preference and (2) exploring the structural and dynamical aspects of the protein in response to divalent-metal-ion substitution or amino acid mutation. Using the X-ray structure of the Cas1 protein from Pseudomonas aeruginosa as a template (PDB 3GOD), we performed (∼2.23 μs) classical molecular dynamics (MD) simulations to compare structural and dynamical differences between Mg2+- and Ca2+-bound binding pockets of wild-type (WT) and mutant (E190A, H254A, D265A, D268A) Cas1. Furthermore, reduced binding pocket models were generated from X-ray and molecular dynamics (MD) trajectories, and the resulting structures were subjected to quantum chemical calculations. Results suggest that Cas1 prefers Mg2+ binding relative to Ca2+ and the preference is the strongest for WT and the weakest for the D268A mutant. Quantum chemical calculations indicate that Mn2+ is the most preferred relative to both Mg2+ and Ca2+ in the wild-type and mutant Cas1. Substitution of Mg2+ by Ca2+ does not alter the interaction network between Cas1 and the divalent metal ion but increases the wetness of the binding pocket by introducing a single water molecule in the first coordination shell of the latter. The strength of metal-ion preference (Mg2+ versus Ca2+) seems to be dependent on the solvent accessibility of the divalent-metal-ion binding pocket, strongest for wild-type Cas1 (in which the metal-ion binding pocket is dry, which includes two water molecules) and the weakest for the D268A mutant (in which the metal-ion binding pocket is wet, which includes four water molecules).
Fingerprint based biometric systems are ubiquitous because they are relatively cheaper to install and maintain, while serving as a fairly accurate biometric trait. However, it has been shown in the past that spoofing attacks on many fingerprint scanners are possible using artificial fingerprints generated using, but not limited to gelatin, Play-Doh and Silicone molds. In this paper, we propose a novel method based on the minutiae count for detecting the fake fingerprints generated using these methods. The proposed algorithm has been tested on the standard FVC (Fingerprint Verification Competition) 2000-2006 dataset and the accuracy was reported to be well above 85%. We also present a literature survey of the previous algorithms for fake fingerprint detection.
Objective-To determine changes in AA production, and transcription of DHEA sulfotransferase (SULT2A1) in the NCI-H295R human adrenocortical cell line in response to insulin and testosterone, an environment mimicking the PCOS state.Design-In vitro experiment using NCI-H295R adrenocortical cell lines. Setting-Academic medical center. Patients-NCI-H295R human adrenocortical cell lineInterventions-The transcriptional activity of SULT2A1 and adrenal steroid production was quantified after exposure to various treatments (e.g. forskolin, insulin, testosterone, and combinations thereof).Main Outcome Measures-Quantification of mRNA for DHEA sulfotransferase (SULT2A1) by real-time reverse transcription-polymerase chain reaction and measurement of steroid production by radioimmunoassay.Results-Testosterone decreased DHEAS and cortisol, and increased DHEA, secretion by H295R cells; the inhibitory effects of testosterone on DHEAS and cortisol production were augmented by insulin. There was a trend towards an increase in the transcription of SULT2A1 by insulin and testosterone.Conclusions-Testosterone and insulin appear to be modulators of AA production in this human adrenocortical cell model. These results suggest that testosterone may augment DHEA secretion in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript the human adrenal, although they do not support the role of this sex steroid or insulin on the elevated DHEAS levels frequently observed in PCOS.
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