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Poghos O. Vardevanyan Ara P. Antonyan Marine A. Parsadanyan Hayk G. Davtyan Zaruhi R. Boyajyan Armen T. Karapetian 《Journal of biomolecular structure & dynamics》2013,31(4):465-470
Abstract The interaction of Ethidium Bromide (EtBr) with double-stranded (ds-) and single-stranded (ss-) poly[d(A-T)] was studied in different ionic strengths solutions. Optical spectroscopy and Scatchard analysis results indicate that the ligand interacts to both helix and coiled structures of the polynucleotide by “strong” and “weak” binding modes. The association parameters (binding constant—K—and the number of nucleotides corresponding to a binding site—n) of the strong type of interaction were found to be independent of Na+ concentration. Weak interaction occurs at low ionic strength and/or high EtBr concentration. Estimated binding parameters of EtBr with ss- and ds-polynucleotide are in good agreement with those for EtBr-B-DNA complexes. Data obtained provided an evidence for a stacking interaction of EtBr with single stranded poly[d(A-T)]. 相似文献
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Xuqi?Chen Shayna?M?Williams-Burris Rebecca?McClusky Tuck?C?Ngun Negar?Ghahramani Hayk?Barseghyan Karen?Reue Eric?Vilain Arthur?P?ArnoldEmail author 《Biology of sex differences》2013,4(1):15
Background
Klinefelter syndrome (KS), caused by XXY karyotype, is characterized by low testosterone, infertility, cognitive deficits, and increased prevalence of health problems including obesity and diabetes. It has been difficult to separate direct genetic effects from hormonal effects in human studies or in mouse models of KS because low testosterone levels are confounded with sex chromosome complement.Methods
In this study, we present the Sex Chromosome Trisomy (SCT) mouse model that produces XXY, XYY, XY, and XX mice in the same litters, each genotype with either testes or ovaries. The independence of sex chromosome complement and gonadal type allows for improved recognition of sex chromosome effects that are not dependent on levels of gonadal hormones. All mice were gonadectomized and treated with testosterone for 3 weeks. Body weight, body composition, and motor function were measured.Results
Before hormonal manipulation, XXY mice of both sexes had significantly greater body weight and relative fat mass compared to XY mice. After gonadectomy and testosterone replacement, XXY mice (both sexes) still had significantly greater body weight and relative fat mass, but less relative lean mass compared to XY mice. Liver, gonadal fat pad, and inguinal fat pad weights were also higher in XXY mice, independent of gonadal sex. In several of these measures, XX mice also differed from XY mice, and gonadal males and females differed significantly on almost every metabolic measure. The sex chromosome effects (except for testis size) were also seen in gonadally female mice before and after ovariectomy and testosterone treatment, indicating that they do not reflect group differences in levels of testicular secretions. XYY mice were similar to XY mice on body weight and metabolic variables but performed worse on motor tasks compared to other groups.Conclusions
We find that the new SCT mouse model for XXY and XYY recapitulates features found in humans with these aneuploidies. We illustrate that this model has significant promise for unveiling the role of genetic effects compared to hormonal effects in these syndromes, because many phenotypes are different in XXY vs. XY gonadal female mice which have never been exposed to testicular secretions.13.
Valerie A. Arboleda Alice Fleming Hayk Barseghyan Emmanuèle Délot Janet S. Sinsheimer Eric Vilain 《Genetics》2014,197(3):885-897
To identify novel genomic regions that regulate sex determination, we utilized the powerful C57BL/6J-YPOS (B6-YPOS) model of XY sex reversal where mice with autosomes from the B6 strain and a Y chromosome from a wild-derived strain, Mus domesticus poschiavinus (YPOS), show complete sex reversal. In B6-YPOS, the presence of a 55-Mb congenic region on chromosome 11 protects from sex reversal in a dose-dependent manner. Using mouse genetic backcross designs and high-density SNP arrays, we narrowed the congenic region to a 1.62-Mb genomic region on chromosome 11 that confers 80% protection from B6-YPOS sex reversal when one copy is present and complete protection when two copies are present. It was previously believed that the protective congenic region originated from the 129S1/SviMJ (129) strain. However, genomic analysis revealed that this region is not derived from 129 and most likely is derived from the semi-inbred strain POSA. We show that the small 1.62-Mb congenic region that protects against B6-YPOS sex reversal is located within the Sox9 promoter and promotes the expression of Sox9, thereby driving testis development within the B6-YPOS background. Through 30 years of backcrossing, this congenic region was maintained, as it promoted male sex determination and fertility despite the female-promoting B6-YPOS genetic background. Our findings demonstrate that long-range enhancer regions are critical to developmental processes and can be used to identify the complex interplay between genome variants, epigenetics, and developmental gene regulation. 相似文献
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Kelleher RJ Geigenmüller U Hovhannisyan H Trautman E Pinard R Rathmell B Carpenter R Margulies D 《PloS one》2012,7(4):e35003
Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism. 相似文献
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Kevin Rezzadeh Bo Zhang Diana Zhu Mark Cubberly Hayk Stepanyan Babar Shafiq Phillip Lim Ranjan Gupta Jacques Hacquebord Kenneth Egol 《The Iowa orthopaedic journal》2022,42(1):63
BackgroundPatients with psychiatric comorbidities represent a significant subset of those sustaining pilon fractures. The purpose of this study is to examine the association of psychiatric comorbidities (PC) in patients with pilon fractures and clinical outcomes.MethodsA multi-institution, retrospective review was conducted. Inclusion/exclusion criteria were skeletally mature patients with a tibia pilon fracture (OTA Type 43B/C) who underwent definitive fracture fixation utilizing open reduction internal fixation (ORIF) with a minimum of 24 weeks of follow-up. Patients were stratified into two groups for comparison: PC group and no PC group.ResultsThere were 103 patients with pilon fractures that met the inclusion/exclusion criteria of this study. Of these patients, 22 (21.4%) had at least one psychiatric comorbidity (PC) and 81 (78.6%) did not have psychiatric comorbidities (no PC). There was a higher percentage of female patients (PC: 59.1% vs no PC: 25.9%, p=0.0.005), smokers (PC: 40.9% vs no PC: 16.0%, p=0.02), and drug users (PC: 22.7% vs no PC: 8.6%, p=0.08) amongst PC patients. Fracture comminution (PC: 54.5% vs no PC: 32.1%, p=0.05) occurred more frequently in PC patients. The PC group had a higher incidence of weightbearing noncompliance (22.7% vs 7.5%, p=0.04) and reoperation (PC: 54.5% vs no PC: 29.6%, p=0.03).ConclusionPatients with psychiatric comorbidities represent a significant percentage of pilon fracture patients and appear to be at higher risk for postoperative complication. Risk factors that may predispose patients in the PC group include smoking/substance use, weightbearing noncompliance, and fracture comminution. Level of Evidence: III 相似文献
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Movsesyan N Ghochikyan A Mkrtichyan M Petrushina I Davtyan H Olkhanud PB Head E Biragyn A Cribbs DH Agadjanyan MG 《PloS one》2008,3(5):e2124