The Role of Sex Hormones in Inducing Maternal Uterine Remodeling and Vasodilation During Pregnancy

Uterine vascular adaptations such as vessel growth and vasodilation are needed to facilitate the more than 10-fold increase of uteroplacental blood flow (UPBF) during pregnancy. Adverse adaptations may result in pregnancy complications such as preeclampsia and intrauterine growth restriction. Pregnancy milieu, placentation and the attendant change in wall shear stress are major regulators of uterine vascular adaptation. In this study, we aimed at delineating : (1) the contribution of these regulators in vascular remodeling and (2) the effects of pregnancy milieu (estrogen and progesterone) alone and in combination with wall shear stress on the vascular reactivity. Using Sprague Dawley rats as the animal model, three surgical methods were utilized: (1) unilateral oviductal ligation (OHL) that restricts pregnancy to one uterine horn; (2) cervical-end main uterine artery and vein ligation (VL) that alters the hemodynamic pattern of the UPBF and wall shear stress; and (3) ovariectomy (OVX) with the implant of estrogen + progesterone pellet (0.5 and 100 mg, respectively). A segment of ovarian-end main uterine artery from each uterine horn was dissected, cannulated, and pressurized in an arteriograph system. Lumen diameters in response to phenylephrine (vasoconstrictor) and acetylcholine (vasodilator) were measured. Passive lumen diameters, wall thickness, vessel cross-sectional area, and distensibility were also measured under a microscope. Significant remodeling was seen in OVX rats in response to hormone replacement (p=0.0457); however, the extent of remodeling did not reach that seen in the nonpregnant horn of OHL rats. No significant change in wall thickness, cross-sectional area or wall: lumen ratio was found in OVX (+pellet), compared to OVX (-pellet) rats. Estrogen + progesterone had no significant effect on the sensitivity to phenylephrine or acetylcholine. In conclusion, estrogen + progesterone does have a significant effect on vascular remodeling. The presence of other factors, such as placentation, likely augment this process

Biological Role and Disease Impact of Copy Number Variation in Complex Disease

In the human genome, DNA variants give rise to a variety of complex phenotypes. Ranging from single base mutations to copy number variations (CNVs), many of these variants are neutral in selection and disease etiology, making difficult the detection of true common or rare frequency disease-causing mutations. However, allele frequency comparisons in cases, controls, and families may reveal disease associations. Single nucleotide polymorphism (SNP) arrays and exome sequencing are popular assays for genome-wide variant identification. To limit bias between samples, uniform testing is crucial, including standardized platform versions and sample processing. Bases occupy single points while copy variants occupy segments. Bases are bi-allelic while copies are multi-allelic. One genome also encodes many different cell types. In this study, we investigate how CNV impacts different cell types, including heart, brain and blood cells, all of which serve as models of complex disease. Here, we describe ParseCNV, a systematic algorithm specifically developed as a part of this project to perform more accurate disease associations using SNP arrays or exome sequencing-generated CNV calls with quality tracking of variants, contributing to each significant overlap signal. Red flags of variant quality, genomic region, and overlap profile are assessed in a continuous score and shown to correlate over 90% with independent verification methods. We compared these data with our large internal cohort of 68,000 subjects, with carefully mapped CNVs, which gave a robust rare variant frequency in unaffected populations. In these investigations, we uncovered a number of loci in which CNVs are significantly enriched in non-coding RNA (ncRNA), Online Mendelian Inheritance in Man (OMIM), and genome-wide association study (GWAS) regions, impacting complex disease. By evaluating thoroughly the variant frequencies in pediatric individuals, we subsequently compared these frequencies in geriatric individuals to gain insight of these variants\u27 impact on lifespan. Longevity-associated CNVs enriched in pediatric patients were found to aggregate in alternative splicing genes. Congenital heart disease is the most common birth defect and cause of infant mortality. When comparing congenital heart disease families, with cases and controls genotyped both on SNP arrays and exome sequencing, we uncovered significant and confident loci that provide insight into the molecular basis of disease. Neurodevelopmental disease affects the quality of life and cognitive potential of many children. In the neurodevelopmental and psychiatric diseases, CACNA, GRM, CNTN, and SLIT gene families show multiple significant signals impacting a large number of developmental and psychiatric disease traits, with the potential of informing therapeutic decision-making. Through new tool development and analysis of large disease cohorts genotyped on a variety of assays, I have uncovered an important biological role and disease impact of CNV in complex disease

i am still holding your hand

i am still holding your hand , a collection of poetry, is the Honors Senior Project by Sophie Glessner

Alexander Glazunov and his Violin Concerto: History, Biography, and Performance Perspective

Alexander Konstantinovich Glazunov, who was born on August 10, 1865, was a highly influential musician and composer in the early 20th century. Despite living well into the 20th century, he adhered to the compositional techniques and ideals of the 19th century. Glazunov generally wrote in a highly romantic style throughout his life, and never gave in to the stylistic pressures of the early 20th century. He worked prolifically in many genres, including symphonies, concertos, tone poems, string quartets, and ballets; however, he wrote relatively little vocal music, and no opera. Glazunov was also a proficient conductor and an excellent pianist. He served a short tenure on the faculty of the St. Petersburg Conservatory starting in 1899, and then he became the director of the conservatory from the end of 1905 to 1928

Pamphlet of Preventative Immunization and Screening Recommendations for Adult Women

This project seeks to consolidate common immunization recommendations and preventative screening recommendations for adult women 18 years and older, based on the U.S. Preventative Services Task Force and Centers for Disease Control and Prevention recommendations. This resource should be offered to patients of the primary care office, with the goal of providing information in a concise and approachable manner that allows patients to review general recommendations on their own, generate questions or express concerns about their health, and encourage patients to advocate for their own health and well-being. With this intervention, the broader goal is to increase immunization rates and adherence to recommended screenings in order to catch and address preventable health conditions sooner.https://scholarworks.uvm.edu/fmclerk/2037/thumbnail.jp

Letter from Kate Glessner Carrithers to John Muir, [ca. 1902] May 21.

My dear Mr Muir.Will you kindly inform me as to the exact title of Clarence King\u27s work on geology (as I understand it) relative to the geology of the Yosemite. If his book would not be helpful perhaps you will suggest something in it\u27s stead, not too technical. Since coming to California03006 your name has grown so familiar and your books have given so much pleasure to me and some friends of mine who are lovers of nature and the free untramelled life you enjoy. We are contemplating a journey to the Yosemite [to?] remain perhaps thru\u27 the summer and wish to enjoy it in the most intelligent way, at least to get a clear idea of its beauty. Mr Lukens, whom we know, has spoken of you so often that I felt not the least fear in asking your assistance.My friends have four new [illegible] and I have [illegible] Mountains of California. We would be delighted if you would suggest others you like.With very great respectKate Glessner Carrithers408 Kensington PlacePasadena Calif.May 21

HIV-associated structural brain changes as related to cognition

Nearly half of all HIV-positive individuals present with some form of HIV-associated neurocognitive disorder (HAND). The experiments described in this thesis examined the structural changes that occur in the brain as a result of HIV infection. While previous work has established that HIV targets the basal ganglia and fronto-striatal systems and impacts cortical and white matter pathways, it was unknown whether these changes occur in the absence of HAND. The studies described here focused on cognitively asymptomatic HIV+ individuals (CAHIV+) without HAND as determined by widely accepted neuropsychological performance guidelines. Experiment 1 utilized diffusion tensor imaging (DTI) to examine HIV-associated alterations in white matter (WM) fractional anisotropy (FA) in the absence of HAND in 23 HIV+ individuals and 17 control participants (HIV-) matched for age, education, and verbal IQ. The hypothesis was that CAHIV+ participants would show lower FA values than HIV- in the corpus callosum, frontotemporal, and parietal regions of interest (ROIs). CAHIV+ individuals demonstrated higher FA in the frontotemporal region and posterior corpus callosum, but lower FA in parietal WM relative to HIV- individuals. Experiment 2 utilized structural MRI to compare cortical thickness in 22 CAHIV+ individuals and 19 control participants (HIV-) matched for age, education, and verbal IQ. The hypothesis was that CAHIV+ participants would have thinner frontal, temporal, and parietal regions than HIV- participants. Reduced cortical thickness measures were identified in the cingulate and superior temporal gyri, with increased cortical thickness measures in the inferior occipital gyrus, for HIV+ participants compared to HIV-. Experiment 3 examined the relationship between the structural alterations identified in Experiments 1 and 2, neuropsychological performance on tests sensitive to HAND identification, and immunological characteristics in 30 HIV+ participants and 28 HIV- control participants. As hypothesized, regional FA values, cortical thickness, and viral load were related to neuropsychological composite scores for CAHIV+, but not HIV-. Together, results from these three studies suggest that regional FA and cortical alterations identified in CAHIV+ patients may contribute to the cognitive deficits often seen in later stages of HIV disease

Common variants in polygenic schizophrenia

Schizophrenia is associated with both common single-nucleotide polymorphisms at the MHC locus and rare copy-number variants affecting many genes