Digital Commons Network^™

Corneal Gene Therapy: Basic Science And Translational Perspective, Rajiv R. Mohan, Jason T. Rodier, Ajay Sharma

Pharmacy Faculty Articles and Research

Corneal blindness is the third leading cause of blindness worldwide. Gene therapy is an emerging technology for corneal blindness due to the accessibility and immune-privileged nature of the cornea, ease of vector administration and visual monitoring, and ability to perform frequent noninvasive corneal assessment. Vision restoration by gene therapy is contingent upon vector and mode of therapeutic gene introduction into targeted cells/tissues. Numerous efficacious vectors, delivery techniques, and approaches have evolved in last decade for developing gene-based interventions for corneal diseases. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, …

Functional Near Infrared Detection Of Real And Imagined Finger Taps Using Support Vector Machine, Linear Discriminant Analysis, And Decision Tree Classification Methods, Eugene A. Stoudenmire

Computational Modeling & Simulation Engineering Theses & Dissertations

This study investigates the thesis that given cerebral response samples of an individual's left, right, both, and imagined finger tapping, continuous wave (CW) functional Near Infrared (fNIR), unregistered with fMRI, can differentiate between any two of the four categories.

Fifty subjects were outfitted with a single source/detector attached to a single, square pad, affixed to their heads using devices such as elastic bands and caps for light shielding. Slides depicting arrows pointing left, right, both directions, or made of dashed lines were presented to each subject, with a slide of text interspersed between each. Subjects tapped with their left finger, …

Secondary Cutaneous Plasmacytoma In A Patient With Multiple Myeloma, Joshua M. Levin Md, Christian W. Oram Do

Department of Medicine

No abstract provided.

Merkel Cell Carcinoma, Cynthia L. Bartus Md, Steven Oberlender Md, Phd, Christian W. Oram Do

Department of Medicine

No abstract provided.

Cognitive Assessment In The Acute Care Patient Postoperative Craniotomy, Melissa Carmody Motrl/L, Mscs, C/Ndt, Sandra M. Tremblay Pt, Ms, Cws, Mscs

Department of Medicine

No abstract provided.

Interrupted Aortic Arch In The Adult, Amit Nanavati Md, Matthew W. Martinez, Nainesh Patel Md

Department of Medicine

No abstract provided.

Pseudo Hyperphosphatemia In Multiple Myeloma, Anshul Kumar, Pradeep Dhakarwal Md, Vibha Agrawal, Tayyab Ali

Department of Medicine

No abstract provided.

St-Segment Elevation (Stemi) Real Time Data Feedback –A Process Of Care Initiative, Orlando E. Rivera Rn, Nainesh Patel Md, Bruce Feldman Do, Mercedes Rios-Scott Bs, David M. Richardson Md, J Patrick Kleaveland Md, David A. Cox Md, Ronald S. Freudenberger Md

Department of Medicine

No abstract provided.

Rapid Door To Balloon Time In The Treatment Of Acute St-Elevation Myocardial Infarction Is Associated With Reduced Length Of Hospital Stay, Amit Nanavati Md, David A. Cox Md, J Patrick Kleaveland Md, Orlando E. Rivera Rn, Nainesh Patel Md

Department of Medicine

No abstract provided.

Visualization And Management Of A Distally Embolized Stent After St-Elevation Myocardial Infarction, Amit Nanavati Md, Nainesh C. Patel Md

Department of Medicine

No abstract provided.

Endovascular Management Of Aortoiliac Occlusive Disease, Nitin Verma Md, Amit Nanavati Md, Bryan W. Kluck Do

Department of Medicine

No abstract provided.

Novel Model Of Care For The Person With Multiple Sclerosis: Physical Therapist In The Neurology Office, Allyn Danni Pt, Ncs, Atp, Mscs, Sandra M. Tremblay Pt, Ms, Cws, Mscs

Department of Medicine

No abstract provided.

Progressive Extra-Oral Static/Dynamic Splint, Lisa Lepage Otr/L, Brian Graeff Ms, Otr/L

Department of Medicine

No abstract provided.

Austrian Syndrome: Triad Of The Past Or Harbinger Of The Future?, Mira Mitry Md, Suzanne J. Templer Do, Stacey Smith Md, Facp, Eugene P. York Md, Facp

Department of Medicine

No abstract provided.

Early Adolescent Nicotine Exposure Has Long-Lasting Effects On Cocaine-Induced Behaviors In Mice, Mai Alajaji

Theses and Dissertations

Nicotine is one of the most commonly used drugs among adolescent populations. Given the fact that adolescence is a unique developmental stage, during which nicotine has long-term effects on future drug-taking behavior, it is essential to understand how early exposure to nicotine during adolescence may affect the abuse liability of other drugs. We hypothesize that repeated exposure to low doses of nicotine in adolescence induce age-specific enhancement of the rewarding effects of several drugs of abuse in the conditioned place preference (CPP) test. Furthermore, we predict that these changes in behavioral responses are mediated by nicotine-induced brain region-specific increases in …

A Genome-Wide Methylation Study On Essential Hypertension In Young African American Males., Xiaoling Wang, Bonita Falkner, Haidong Zhu, Huidong Shi, Shaoyong Su, Xiaojing Xu, Ashok Kumar Sharma, Yanbin Dong, Frank Treiber, Bernard Gutin, Gregory Harshfield, Harold Snieder

Department of Medicine Faculty Papers

OBJECTIVE: There is emerging evidence from animal studies suggesting a key role for methylation in the pathogenesis of essential hypertension. However, to date, very few studies have investigated the role of methylation in the development of human hypertension, and none has taken a genome-wide approach. Based on the recent studies that highlight the involvement of inflammation in the development of hypertension, we hypothesize that changes in DNA methylation of leukocytes are involved in the pathogenesis of hypertension.

METHOD & RESULTS: We conducted a genome-wide methylation analysis on 8 hypertensive cases and 8 normotensive age-matched controls aged 14-23 years and performed …

Copper Triflate-Mediated Synthesis Of 1,3,5-Triarylpyrazoles In [Bmim][Pf6] Ionic Liquid And Evaluation Of Their Anticancer Activities, V. Kameshwara Rao, Rakesh Tiwari, Bhupender S. Chhikara, Amir Nasrolahi Shirazi, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

A simple, efficient, and environment friendly protocol for the synthesis of 1,3,5-triarylpyrazoles and 1,3,5-triarylpyrazolines in [bmim][PF6] ionic liquid mediated by Cu(OTf)2 is described. The reaction protocol gave 1,3,5-triarylpyrazoles in good to high yields (71–84%) via a one-pot addition–cyclocondensation between chalcones and arylhydrazines, and oxidative aromatization without the requirement for an additional oxidizing reagent. The catalyst can be reused for up to four cycles without much loss in the catalytic activity. The pyrazoles (4a–o) and pyrazolines (3a–n) were evaluated for their antiproliferative activity in SK-OV-3, HT-29, and HeLa human cancer cells lines. Among all the compounds, 3b inhibited cell proliferation of …

Impairment Of Trkb-Psd-95 Signaling In Angelman Syndrome, Cong Cao, Mengia S. Rioult-Pedotti, Paolo Migani, Crystal J. Yu, Rakesh Tiwari, Keykavous Parang, Mark R. Spaller, Dennis J. Goebel, John Marshall

Pharmacy Faculty Articles and Research

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) …

Regulation Of The Mouse And Human Β-Globin Genes By Krüppel Like Transcription Factors Klf1 And Klf2, Yousef N. Alhashem

Theses and Dissertations

Krüppel-like factors KLF1 and KLF2 are closely related transcription factors with three zinc finger domains in their carboxy-termini. KLF1 (erythroid Krüppel-like factor, or EKLF) plays essential roles in embryonic and adult erythropoiesis. KLF2 is a positive regulator of the mouse and human embryonic β- globin genes. KLF1 and KLF2 have overlapping roles in embryonic erythropoiesis, as demonstrated using single and double knockout (KO) mouse models. Ablation of the KLF1 or KLF2 gene causes embryonic lethality, and double KO embryos are more anemic and die sooner than either single KO. We have shown that KLF1 and KLF2 positively regulate the human …

Acute Hypersensitivity Of Pluripotent Testicular Cancer-Derived Embryonal Carcinoma To Low-Dose 5-Aza Deoxycytidine Is Associated With Global Dna Damage-Associated P53 Activation, Anti-Pluripotency And Dna Demethylation, Bijesh K. Biswal, Maroun J. Beyrouthy, Mary P. Hever-Jardine, David Armstrong, Craig R. Tomlinson, Brock C. Christensen, Carmen J. Marsit, Michael J. Spinella

Dartmouth Scholarship

Human embryonal carcinoma (EC) cells are the stem cells of nonseminoma testicular germ cells tumors (TGCTs) and share remarkable similarities to human embryonic stem (ES) cells. In prior work we found that EC cells are hypersensitive to low nanomolar doses of 5-aza deoxycytidine (5-aza) and that this hypersensitivity partially depended on unusually high levels of the DNA methyltransferase, DNMT3B. We show here that low-dose 5-aza treatment results in DNA damage and induction of p53 in NT2/D1 cells. In addition, low-dose 5-aza results in global and gene specific promoter DNA hypomethylation. Low- dose 5-aza induces a p53 transcriptional signature distinct from …

Multiple Subject Barycentric Discriminant Analysis (Musubada): How To Assign Scans To Categories Without Using Spatial Normalization, Hervé Abdi, Lynne J. Williams, Andrew C. Connolly, M. Ida Gobbini

Dartmouth Scholarship

We present a new discriminant analysis (DA) method called Multiple Subject Barycentric Discriminant Analysis (MUSUBADA) suited for analyzing fMRI data because it handles datasets with multiple participants that each provides different number of variables (i.e., voxels) that are themselves grouped into regions of interest (ROIs). Like DA, MUSUBADA (1) assigns observations to predefined categories, (2) gives factorial maps displaying observations and categories, and (3) optimally assigns observations to categories. MUSUBADA handles cases with more variables than observations and can project portions of the data table (e.g., subtables, which can represent participants or ROIs) on the factorial maps. Therefore MUSUBADA can …

Human Calmodulin Methyltransferase: Expression, Activity On Calmodulin, And Hsp90 Dependence, Sophia Magen, Roberta Magnani, Sitvanit Haziza, Eli Hershkovitz, Robert Houtz, Franca Cambi, Ruti Parvari

Horticulture Faculty Publications

Deletion of the first exon of calmodulin-lysine N-methyltransferase (CaM KMT, previously C2orf34) has been reported in two multigene deletion syndromes, but additional studies on the gene have not been reported. Here we show that in the cells from 2p21 deletion patients the loss of CaM KMT expression results in accumulation of hypomethylated calmodulin compared to normal controls, suggesting that CaM KMT is essential for calmodulin methylation and there are no compensatory mechanisms for CaM methylation in humans. We have further studied the expression of this gene at the transcript and protein levels. We have identified 2 additional …

The Role Of Dairy Products And Milk In Adolescent Obesity: Evidence From Hong Kong’S ‘‘Children Of 1997’’ Birth Cohort, Shi Lin Lin, Marie Tarrant, Lai Ling Hui, Man Ki Kwok, Tai Hing Lam, Gabriel M. Leung, Mary Schooling

Publications and Research

Background
Observational studies, mainly from Western populations, suggest dairy consumption is inversely associated with adiposity. However, in these populations the intake range is limited and both diet and obesity may share social patterning. Evidence from non-Western developed settings with different social patterning, is valuable in distinguishing whether observed associations are biologically mediated or socially confounded.

Objective
To examine the associations of milk or other dairy product consumption with adolescent obesity.

Methods
We used multivariable linear regression models to examine the associations of milk or other dairy product consumption, obtained from a food frequency questionnaire, at 11 years with body mass …

Association Of Genetic Variation, Gene Expression, And Protein Abundance Within The Natriuretic Peptide Pathway, Bipin Sunkara

Honors College Theses

Background: The natriuretic peptide (NP) system is a critical physiologic pathway in heart failure, but there is marked individual variability in its functioning which may be genetic in origin. We investigated how genetic variations in NP pathway genes correlate with gene expression and protein abundance.

Methods: DNA, RNA, and tissue from human kidney (n=77) were obtained. Kidney was chosen as target tissue because each of the four candidate genes and proteins (natriuretic peptide receptor 1 (NPR1), NPR2, NPR3 and membrane metallo-endopeptidase (MME)) are expressed there. DNA samples were genotyped for 120 single nucleotide polymorphisms (SNP) in these four genes using …

Multiple Regulatory Mechanisms Control B-1 B Cell Activation, Vishal Sindhava, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells constitute a unique subset of B cells identified in several species including mice and humans. B-1 cells are further subdivided into B-1a and B-1b subsets as the former but not the later express CD5.The B-1a subset contributes to innate type of immune responses while the B-1b B cell subset contributes to adaptive responses. B-1 cell responses to B cell receptor (BCR) as well as Toll-like receptor (TLR) ligation are tightly regulated due to the cross-reactivity of antigen specific receptors on B-1 cells to self-antigens. B-1 cells are elevated in several autoimmune diseases. CD5 plays a major role in …

Luteolin Inhibits Human Prostate Tumor Growth By Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis, Poyil Pratheeshkumar, Young-Ok Son, Amit Budhraja, Xin Wang, Songze Ding, Lei Wang, Andrew Hitron, Jeong-Chae Lee, Donghern Kim, Sasidharan Padmaja Divya, Gang Chen, Zhuo Zhang, Jia Luo, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is essential for tumor growth, invasion, and metastasis. Luteolin is a common dietary flavonoid found in fruits and vegetables. We studied the antiangiogenic activity of luteolin using in vitro, ex vivo, and in vivo models. In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) …

Targeted Disruption Of Adamts16 Gene In A Rat Genetic Model Of Hypertension, Kathirvel Gopalakrishnan, Sivarajan Kumarasamy, Shakila Abdul-Majeed, Andrea L. Kalinoski, Eric E. Morgan, Amira F. Gohara, Surya M. Nauli, Wanda E. Filipiak, Thomas L. Saunders, Bina Joe

Pharmacy Faculty Articles and Research

A disintegrin-like metalloproteinase with thrombospondin motifs-16 (Adamts16) is an important candidate gene for hypertension. The goal of the present study was to further assess the candidacy of Adamts16 by targeted disruption of this gene in a rat genetic model of hypertension. A rat model was generated by manipulating the genome of the Dahl Salt-sensitive (S) rat using zinc-finger nucleases, wherein the mutant rat had a 17 bp deletion in the first exon of Adamts16, introducing a stop codon in the transcript. Systolic blood pressure (BP) of the homozygous Adamts16(mutant) rats was lower by 36 mmHg compared with the BP of …

From Linkage To Gwas: A Multifaceted Exploration Of The Genetic Risk For Alcohol Dependence, Amy Adkins

Theses and Dissertations

Family, twin and adoption studies consistently suggest that genetic factors strongly influence the risk for alcohol dependence (AD). Although the literature supports the role of genetics in AD, identification of specific genes contributing to the etiology of AD has proven difficult. These difficulties are due in part to the complex set of risk factors contributing to the development of AD. These risk factors include comorbidities with other clinical diagnoses and behavioral phenotypes (e.g., major depression), physiological differences that contribute to the differences between people in their level of response to ethanol (e.g., initial sensitivity) and finally the large number of …

Degeneration Of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits Following Mid-Cervical Spinal Contusion In Mice., Charles Nicaise, Rajarshi Putatunda, Tamara J Hala, Kathleen A Regan, David M Frank, Jean-Pierre Brion, Karelle Leroy, Roland Pochet, Megan C Wright, Angelo C Lepore

Department of Neuroscience Faculty Papers

A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron-diaphragm circuitry. We have …

Depletion Of Endothelial Or Smooth Muscle Cell-Specific Angiotensin Ii Type 1a Receptors Does Not Influence Aortic Aneurysms Or Atherosclerosis In Ldl Receptor Deficient Mice, Debra L. Rateri, Jessica J. Moorleghen, Victoria Knight, Anju Balakrishnan, Deborah A. Howatt, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Whole body genetic deletion of AT1a receptors in mice uniformly reduces hypercholesterolemia and angiotensin II-(AngII) induced atherosclerosis and abdominal aortic aneurysms (AAAs). However, the role of AT1a receptor stimulation of principal cell types resident in the arterial wall remains undefined. Therefore, the aim of this study was to determine whether deletion of AT1a receptors in either endothelial cells or smooth muscle cells influences the development of atherosclerosis and AAAs.

METHODOLOGY/PRINCIPAL FINDINGS: AT1a receptor floxed mice were developed in an LDL receptor -/- background. To generate endothelial or smooth muscle cell specific deficiency, AT1a receptor floxed mice were bred with …