Publications

Genetic polymorphisms in β1-, β2- and β3-adrenergic receptors (β-ARs) have been associated with chronic non-communicable disorders, such as cardiovascular diseases, asthma, chronic obstructive pulmonary disease (COPD) and obesity, as well as β-agonists and antagonists response and toxicity. The purpose of this study was to determine the frequency distribution of ADRB1 genetic variants Ser49Gly and Arg389Gly, ADRB2 variants Gly16Arg and Gln27Glu, ADRB3 variant Trp64Arg in a Southeastern European Caucasian (SEC) population sample and to establish a comparison with existing data from other human populations. A sample of 431 men and 590 women volunteered to participate in this genotyping analysis after anonymization and de-identification. Real Time PCR (Melting Curve Analysis) followed DNA extraction from buccal swabs and statistical analysis of the results was performed. The allele frequencies in the SEC population were Ser49 (90.3%), Arg389 (69.49%), Gly16 (61.61%), Gln27 (65.72%) and Trp64 (94.52%), while a Hardy-Weinberg Equilibrium (HWE) was detected in the population studied. Comparisons for the Ser49Gly, Gln27Glu and Trp64Arg allele distributions demonstrated significant differences between SEC and the European group. European subgroups comparisons showed that allele distributions were similar for 4 of the 5 SNPs between SEC and Southwestern European Caucasians (SWC), while they were quite distinct from the Northwestern European Caucasians (NWC). These data underline the importance of interethnic variability of β-ARs genetic polymorphisms.

Smoak, B. L.; Villanueva, V. G.; Kalogeras, K.; Chrousos, G. P.; Deuster, P. A. Author Information

Abstract Intrauterine growth restriction (IUGR) has been associated with increased perinatal morbidity, higher incidence of neurodevelopmental defects and increased risk for adult metabolic syndrome manifestations. Altered protein expression profiles associated with IUGR may be informative on the pathological mechanisms of this condition and might reveal potential markers for postnatal complications. We hypothesized that nutrient manipulation of the pregnant rat might influence the expression of important neurodevelopmental proteins in the resultant IUGR offspring. Therefore, we aimed to determine in newborn rat brain tissue the expression of collapsin response mediator proteins (CRMPs)‐1, ‐2 and ‐5, commonly referred to as dihydropyrimidinase‐related proteins (DPYLs) – playing a role in axon guidance, invasive growth and cell migration – and compare it to the corresponding expression in control rats. Two‐dimensional electrophoresis and mass spectrometry, as well as Western blot analysis were employed in brain tissue from 24 IUGR newborn rats and 24 controls. With both methods, CRMP‐1, CRMP‐2 and CRMP‐5 were decreased in the brains of the IUGR group as compared to the control group at the time of delivery. In conclusion, IUGR rat offspring are born with a decreased expression of CRMPs, suggesting that these proteins may be implicated in fetal stress‐induced programming.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with insulin resistance, even in the absence of overweight/obesity. The aim of the present study is to examine the global serum proteomic profile of adolescent, normal-weight females with PCOS in order to gain novel insight in the association of this endocrine disorder with insulin physiology and to identify novel circulating markers that can guide intervention protocols.Non-depleted serum from normal-weight (BMI: 18-23 kg m-2 ), adolescent females (13-21 years old) with PCOS (n = 20) is compared to BMI- and age-matched healthy controls (n = 20) using our 3D quantitative proteomics methodology. Serum samples from study participants are randomly pooled to form four biological replicates of females with PCOS and four of healthy controls (n = 5 per sample pool).One-hundred and twenty-six proteins are differentially expressed in females with PCOS compared to controls. Gene ontology analysis shows significant enrichment for terms related to inflammatory immune response, metabolism and insulin-like growth factor receptor signaling pathway. Circulating levels of IGF-1 and -2 and IGFBP-2, -3, and -4 are found to be lower in females with PCOS compared to healthy controls.The present serum proteomics study provides insight into the pro-inflammatory status and insulin dysregulation in young females with PCOS and identifies potential serological markers that can guide early intervention protocols.

In performance‐based earthquake wngineering, record selection comes into play at the interface of seismic hazard and structural analysis aiming to repair any loss of essential seismological dependencies caused by the choice of an insufficient intensity measure to be used for structural response prediction. Site‐specific selection is best exemplified by the prominent conditional spectrum (CS) approach that attempts to ensure a hazard‐consistent response prediction by involving site hazard disaggregation. Specifically, CS utilizes a target spectrum (with mean and dispersion) that, in its latest formulation, accounts for all the scenarios (in terms of magnitude, M , and closest to rupture distance, R ) contributing to the hazard of the site at a given intensity level. The ground motion records, however, are selected to match this target spectrum–based solely on their spectral shape but with no explicit consideration to their underlying M‐R characteristics. The main focus of this study is to explore whether the reintroduction of M‐R criteria in the selection process preserves hidden dependencies that may otherwise be lost through a spectral‐shape‐only proxy. The proposed record selection method, termed CS‐MR, offers a simple approach to maintain a higher order of hazard consistency able to indirectly account for metrics that depend on M‐R (e.g., duration, Arias intensity) but are not captured in the response spectra. Herein the CS‐MR response prediction is favorably compared to CS and to the generalized conditional intensity measure methods that select records according to, respectively, spectral shape only and, for the case at hand, to spectral shape plus duration.

A method is presented for the design of unbonded post-tensioned concrete walls for seismic loading to satisfy multiple performance objectives. It takes advantage of the fact that the initial stiffness of the wall is nearly independent of the amount of post-tensioning reinforcement, and thus the fundamental period of the building can be considered to be a stable parameter in design of walls of a given cross section, independent of the degree of post-tensioning. The design spectra used to follow the specification provided in Eurocode 8 considering the probability of exceedance of the seismic action. A detailed example is provided.

The authors studied CSF corticotropin-releasing hormone (CRH) and plasma cortisol in 22 depressed patients and 18 normal control subjects. CRH levels were similar in the two groups. Depressed patients who were nonsuppressors on the dexamethasone suppression test had significantly higher levels of CRH than suppressors did. The depressed patients' CRH levels were significantly correlated with 4:00 p.m. postdexamethasone plasma cortisol levels. While the inclusion of a depressed patient with an outlier CRH value resulted in the loss of statistical significance for both of these findings, the authors suggest that these results support the hypothesis that hypercortisolism in depressed patients in part reflects a defect at or above the hypothalamus, resulting in hypersecretion of CRH.