Digital Commons Network^™

Comparison Of Cone Mosaic Metrics From Images Acquired With The Spectralis High Magnification Module And Adaptive Optics Scanning Light Ophthalmoscopy, Niamh Wynne, Heather Heitkotter, Erica N. Woertz, Robert F. Cooper, Joseph Carroll

Biomedical Engineering Faculty Research and Publications

Purpose: To compare cone mosaic metrics derived from adaptive optics scanning light ophthalmoscopy (AOSLO) images with those derived from Heidelberg Engineering SPECTRALIS High Magnification Module (HMM) images.

Methods: Participants with contiguous cone mosaics had HMM imaging performed at locations superior and temporal to the fovea. These images were registered and averaged offline and then aligned to split-detection AOSLO images; 200 × 200-µm regions of interest were extracted from both modalities. Cones were semi-automatically identified by two graders to provide estimates of cone density and spacing.

Results: Thirty participants with contiguous cone mosaics were imaged (10 males, 20 females; age range, …

Rare Copy Number Variants In Nrxn1 And Cntn6 Increase Risk For Tourette Syndrome, Alden Y. Huang, Dongmei Yu, Lea K. Davis, Jae Hoon Sul, Fotis Tsetsos, Vasily Ramensky, Ivette Zelaya, Eliana Marisa Ramos, Lisa Osiecki, Jason A. Chen, Lauren M. Mcgrath, Cornelia Illmann, Paul Sandor, Cathy L. Barr, Marco Grados, Harvey S. Singer, Marcus M. Nöthen, Johannes Hebebrand, Robert A. King, Yves Dion, Guy Rouleau, Cathy L. Budman, Christel Depienne, Yulia Worbe, Andreas Hartmenn, Kirsten R. Müller-Vahl, Manfred Stuhrmann, Harald Aschauer, Mara Stamenkovic, Monika Schloegelhofer, Anastasios Konstantinidis, Gholson J. Lyon, William M. Mcmahon, Csaba Barta, Zsanett Tarnok, Peter Nagy, James R. Batterson, Renata Rizzo, Danielle C. Cath, Tomasz Wolanczyk, Cheston Berlin, Irene A. Malaty, Michael S. Okun, Douglas W. Woods, Elliott Rees, Carlos N. Pato, Michele T. Pato, James A. Knowles, Danielle Posthuma, David L. Pauls, Nancy J. Cox, Benjamin M. Neale, Nelson B. Freimer, Peristera Paschou, Carol A. Mathews, Jeremiah M. Scharf, Giovanni Coppola

Psychology Faculty Research and Publications

Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2.28, 95% CI [1.39–3.79], p = 1.2 × 10⁻³) and known, pathogenic CNVs (OR = 3.03 [1.85–5.07], p = 1.5 × 10⁻⁵). We also identified two individual, genome-wide significant loci, each conferring …

Interleukin-1 Receptor Antagonist Polymorphism And Birth Timing: Pathway Analysis Among African American Women, Shannon L. Gillespie, Jeremy L. Neal, Lisa Christian, Laura A. Szalacha, Donna O. Mccarthy, Pamela J. Salsberry

College of Nursing Faculty Research and Publications

Background: Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking.

Objectives: We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or …

Identification Of Multiple Functional Receptors For Tyramine On An Insect Secretory Epithelium, Haiying Zhang, Edward M. Blumenthal

Biological Sciences Faculty Research and Publications

The biogenic amine tyramine (TA) regulates many aspects of invertebrate physiology and development. Although three TA receptor subtypes have been identified (TAR1-3), specific receptors have not been linked to physiological responses in native tissue. In the Malpighian (renal) tubule of Drosophila melanogaster, TA activates a transepithelial chloride conductance, resulting in diuresis and depolarization of the transepithelial potential. In the current work, mutation or RNAi-mediated knockdown in the stellate cells of the tubule of TAR2 (tyrR, CG7431) resulted in a dramatic reduction, but not elimination, of the TA-mediated depolarization. Mutation or knockdown of TAR3 (tyrRII, …

Impact Of Myh6 Variants In Hypoplastic Left Heart Syndrome, Aoy Tomita-Mitchell, Karl D. Stamm, Donna K. Mahnke, Min-Su Kim, Pip M. Hidestrand, Huan-Ling Liang, Mary Goetsch, Pippa Simpson, Andrew N. Pelech, James S. Tweddell, D. Woodrow Benson, John Lough, Michael E. Mitchell

Mathematics, Statistics and Computer Science Faculty Research and Publications

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging …

Impact Of Myh6 Variants In Hypoplastic Left Heart Syndrome, Aoy Tomita-Mitchell, Karl D. Stamm, Donna K. Mahnke, Min-Su Kim, Pip M. Hidestrand, Huan-Ling Liang, Mary A. Goetsch, Mats Hidestrand, Pippa Simpson, Andrew N. Pelech, James S. Tweddell, D. Woodrow Benson, John Lough, Michael Mitchell

Mathematics, Statistics and Computer Science Faculty Research and Publications

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging …

Photoreceptor Inner Segment Morphology In Best Vitelliform Macular Dystrophy, Drew Scoles, Yusufu N. Sulai, Robert F. Cooper, Brian P. Higgins, Ryan D. Johnson, Joseph Carroll, Alfredo Dubra, Kimberly E. Stepien

Biomedical Engineering Faculty Research and Publications

PURPOSE

To characterize outer retina structure in best vitelliform macular dystrophy (BVMD) and to determine the effect of macular lesions on overlying and adjacent photoreceptors.

METHODS

Five individuals with BVMD were followed prospectively with spectral domain optical coherence tomography and confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). The AOSLO cone photoreceptor mosaic images were obtained within and around retinal lesions. Cone density was measured inside and outside lesions. In 2 subjects, densities were compared with published measurements acquired ∼2.5 years before. One subject was imaged 3 times over a 5-month period.

RESULTS

The AOSLO imaging demonstrated that …

Genomics And Autism Spectrum Disorder, Norah L. Johnson

College of Nursing Faculty Research and Publications

Purpose: To present the current state of the evidence regarding translation of genetics (the study of single genes) and genomics (the study of all genes and gene-gene or gene-environment interactions) into health care of children with autism spectrum disorder (ASD).

Methods: This article presents an overview of ASD as an international health challenge, the emerging science related to broad diagnostic criteria, and the role of the nurse in research, education, and practice.

Findings: Much progress is being made in the understanding of genetics and genomics of ASD. Environmental factors are thought to contribute to the risk of developing ASD by …

Human Gene Copy Number Spectra Analysis In Congenital Heart Malformations, Aoy Tomita-Mitchell, Donna K. Mahnke, Craig Struble, Maureen E. Tuffnell, Karl D. Stamm, Mats Hidestrand, Susan Harris, Mary A. Goetsch, Pippa Simpson, David P. Bick, Ulrich Broeckel, Andrew N. Pelech, James S. Tweddell, Michael Mitchell

Mathematics, Statistics and Computer Science Faculty Research and Publications

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 …

The Last Shall Be First: Human Potential In Genetic And Theological Perspectives, M. Therese Lysaught

Theology Faculty Research and Publications

The notion of “human potential” provides a fruitful window through which to explore the competing conceptual frameworks of contemporary genetics and Christianity. The contemporary cultural frame of genetics conceives of human potential in a broadly positive manner: the source of personal and societal flourishing is located within individual bodies, waiting to be identified and unleashed by genetic science and medicine for the good of persons and society. In the Judeo-Christian narrative, human individual, biological potential is far less relevant—and, in fact, may be construed as an impediment to the achievement of personal and social flourishing. Implications for the dialogue between …

Converting Glx2-1 Into An Active Glyoxalase Ii, Pattraranee Limphong, Nicole E. Adams, Matthew F. Rouhier, Ross M. Mckinney, Melissa Naylor, Brian Bennett, Christopher A. Makaroff, Michael W. Crowder

Physics Faculty Research and Publications

Arabidopsis thaliana glyoxalase 2-1 (GLX2-1) exhibits extensive sequence similarity with GLX2 enzymes but is catalytically inactive with SLG, the GLX2 substrate. In an effort to identify residues essential for GLX2 activity, amino acid residues were altered at positions 219, 246, 248, 325, and 328 in GLX2-1 to be the same as those in catalytically active human GLX2. The resulting enzymes were overexpressed, purified, and characterized using metal analyses, fluorescence spectroscopy, and steady-state kinetics to evaluate how these residues affect metal binding, structure, and catalysis. The R246H/N248Y double mutant exhibited low level S-lactoylglutathione hydrolase activity, while the R246H/N248Y/Q325R/R328K mutant exhibited …

Human Glyoxalase Ii Contains An Fe(Ii)Zn(Ii) Center But Is Active As A Mononuclear Zn(Ii) Enzyme, Pattraranee Limphong, Ross M. Mckinney, Nicole E. Adams, Brian Bennett, Christopher A. Makaroff, Thusitha Gunasekera, Michael W. Crowder

Physics Faculty Research and Publications

Human glyoxalase II (Glx2) was overexpressed in rich medium and in minimal medium containing zinc, iron, or cobalt, and the resulting Glx2 analogues were characterized using metal analyses, steady-state and pre-steady-state kinetics, and NMR and EPR spectroscopies to determine the nature of the metal center in the enzyme. Recombinant human Glx2 tightly binds nearly 1 equiv each of Zn(II) and Fe. In contrast to previous reports, this study demonstrates that an analogue containing 2 equiv of Zn(II) cannot be prepared. EPR studies suggest that most of the iron in recombinant Glx2 is Fe(II). NMR studies show that Fe(II) binds to …

Metal Content Of Metallo-Β-Lactamase L1 Is Determined By The Bioavailability Of Metal Ions, Zhenxin Hu, Thusitha S. Gunasekera, Lauren J. Spadafora, Brian Bennett, Michael W. Crowder

Physics Faculty Research and Publications

In an effort to probe whether the metal content of metallo-β-lactamase L1 is affected by metal ion bioavailability, L1 was overexpressed as mature protein (M-L1) and full-length (FL-L1) analogues, and the analogues were characterized with metal analyses, kinetics, and EPR spectroscopy. FL-L1, containing the putative leader sequence, was localized in the periplasm of Escherichia coli and shown to bind Zn(II) preferentially. The metal content of FL-L1 could be altered if the enzyme was overexpressed in minimal medium containing Fe and Mn, and surprisingly, an Fe-binding analogue was obtained. On the other hand, M-L1, lacking the putative leader sequence, was localized …

Changes In Pulmonary Arterial Wall Mechanical Properties And Lumenal Architecture With Induced Vascular Remodeling, Robert C. Molthen, Amy Heinrich, Steven Thomas Haworth, Christopher A. Dawson

Biomedical Engineering Faculty Research and Publications

To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal …

Craniofacial Morphology And Occlusal Variation In Monozygous And Dizygous Twins, William K. Lobb

School of Dentistry Faculty Research and Publications

A study of 60 pairs of twins, 30 monozygous and 30 dizygous, finding a strong genetic component overlaid by functional adaptation most prominent in the dental area.