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Mitochondrial Function Assessed By 31p Mrs And Bold Mri In Non-Obese Type 2 Diabetic Rats, Yuchi Liu, Xunbai Mei, Jielei Li, Nicola Lai, Xin Yu

Electrical & Computer Engineering Faculty Publications

The study aims to characterize age-associated changes in skeletal muscle bioenergetics by evaluating the response to ischemia-reperfusion in the skeletal muscle of the Goto-Kakizaki (GK) rats, a rat model of non-obese type 2 diabetes (T2D). ³¹P magnetic resonance spectroscopy (MRS) and blood oxygen level-dependent (BOLD) MRI was performed on the hindlimb of young (12 weeks) and adult (20 weeks) GK and Wistar (control) rats. ³¹P-MRS and BOLD-MRI data were acquired continuously during an ischemia and reperfusion protocol to quantify changes in phosphate metabolites and muscle oxygenation. The time constant of phosphocreatine recovery, an index of mitochondrial oxidative capacity, …

A Synthetic Porcine Reproductive And Respiratory Syndrome Unprecedented Levels Of Heterologous Protection, Hiep Vu, Fangrui Ma, William W. Laegreid, Asit K. Pattnaik, David Steffen, Alan R. Doster, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Current vaccines do not provide sufficient levels of protection against divergent porcine reproductive and respiratory syndrome virus (PRRSV) strains circulating in the field, mainly due to the substantial variation of the viral genome. We describe here a novel approach to generate a PRRSV vaccine candidate that could confer unprecedented levels of heterologous protection against divergent PRRSV isolates. Using a set of 59 non-redundant, full genome sequences of type-2 PRRSV, a consensus genome (designated as PRRSV-CON) was these 59 PRRSV full genome sequences, followed by selecting the most common nucleotide found at each position of the alignment. Next, the synthetic PRRSV-CON …

Host Cell Functions In Vesicular Stomatitis Virus Replication, Phat X. Dinh, Anshuman Das, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Vesicular stomatitis virus (VSV), the prototypic rhabdovirus, has been used as an excellent paradigm for understanding the mechanisms of virus replication, pathogenesis, host response to virus infection and also for myriads of studies on cellular and molecular biology. Biochemical studies as well as high-throughput genomics, proteomics, and chemical approaches have revealed a plethora of cellular factors and pathways that regulate replication of VSV. These factors include those that support virus replication and also those that restrict its replication. This chapter discusses the role(s) of many of these host cell factors and pathways involved in VSV replication. Although mechanistic understanding of …

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses, Catherine M. Crosby, William E. Matchett, Stephanie S. Anguiano-Zarate, Christopher A. Parks, Eric A. Weaver, Larry R. Pease, Richard J. Webby, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Head-to-head comparisons of conventional influenza vaccines with ade- novirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we de- veloped “single-cycle” adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than …

From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xinquan Wang, Sulan Luo

School of Veterinary and Biomedical Sciences: Faculty Publications

Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking …

From Crystal Structure Of Α-Conotoxin Gic In Complex With Ac-Achbp To Molecular Determinants Of Its High Selectivity For Α3Β2 Nachr, Bo Lin, Manyu Xu, Xiaopeng Zhu, Yong Wu, Xi Liu, Dongting Zhangsun, Yuanyan Hu, Shi-Hua Xiang, Igor E. Kasheverov, Victor I. Tsetlin, Xianquan Wang, Sulan Luo

School of Veterinary and Biomedical Sciences: Faculty Publications

Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking …

Voxel Based Morphometry In Optical Coherence Tomography: Validation & Core Findings, Bhavna J. Antony, Min Chen, Aaron Carass, Bruno M. Jedynak, Omar Al-Louzi, Sharon D. Solomon, Shiv Saidha, Peter Calabresi, Jerry L. Prince

Mathematics and Statistics Faculty Publications and Presentations

Optical coherence tomography (OCT) of the human retina is now becoming established as an important modality for the detection and tracking of various ocular diseases. Voxel based morphometry (VBM) is a long standing neuroimaging analysis technique that allows for the exploration of the regional differences in the brain. There has been limited work done in developing registration based methods for OCT, which has hampered the advancement of VBM analyses in OCT based population studies. Following on from our recent development of an OCT registration method, we explore the potential benefits of VBM analysis in cohorts of healthy controls (HCs) and …

The Relationship Between Blood Urea Nitrogen Levels And Metabolic, Biochemical, And Histopathologic Findings Of Nondiabetic, Nonhypertensive Patients With Nonalcoholic Fatty Liver Disease, Cemal Nuri̇ Erçi̇n, Teoman Doğru, Gürkan Çelebi̇, Hasan Gürel, Hali̇l Genç, Erdi̇m Sertoğlu, Sai̇t Bağci

Turkish Journal of Medical Sciences

Background/aim: Nonalcoholic fatty liver disease (NAFLD) is known as the most common cause of chronic liver disease. It is accepted that the leading cause of death in patients with NAFLD is from coronary events. Blood urea nitrogen (BUN) was used as a prognostic indicator for cardiovascular disease. We aimed to investigate the relationship between BUN levels and metabolic, biochemical, and histopathologic findings of nondiabetic patients with NAFLD. Materials and methods: A total of 195 male patients with biopsy proven NAFLD and 82 healthy controls with normal liver and renal function tests and normal abdominal ultrasonography were enrolled in the study. …

Temporal Trends Of Corporate Sponsorship In Medical Research, Elijah Bodey

Honors Projects

Data will be collected from medical journals to assessed changes in the nature and prevalence of corporate sponsorship. The journals that will be reviewed are the Journal of the American Medical Association (JAMA), the New England Journal of Medicine (NEJM), the British Medical Journal (BMJ), and the Lancet. These journals were chosen because of their high impact on medical research representing both American and British Medical editorials. It has been shown that corporate sponsorship has been associated with bias results (Kjaergard et al 2002). Changes in the nature of corporate sponsorship would be linked to changes in economic climate and …

The Challenge Of Analyzing The Results Of Next-Generation Sequencing In Children., Isabelle Thiffault, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

In recent years, next-generation sequencing technologies have revolutionized approaches to genetic studies. Whole-exome or whole-genome sequencing allows diagnoses in many patients who have complex phenotypes and unusual clinical presentations. As genomic and exomic testing expands in both the research and clinical settings, pediatricians will need to understand the technology of next-generation sequencing and the complexity of interpreting genomic variants relevant to patient phenotypic features. This article briefly explains the technology by which genomes are sequenced and discusses some of the complexity related to interpreting genomic variants. We conclude with some thoughts on the clinical applications of such testing.

Medical Community Distrust And The Influenza Vaccination Rates Of Black Americans, Kenyatte Irby Winston

Walden Dissertations and Doctoral Studies

Black Americans experience influenza vaccination rates that are lower than the rates of other ethnic groups. Low influenza vaccination rates among the Black community are associated with higher influenza infection rates, influenza-related hospitalizations, and higher influenza mortality rates. There is a belief within the Black American community that the medical establishment does not have the Black American patient in its best interest, leading to feelings of distrust. The purpose of this study was to determine if the distrust of the medical community is a relevant factor in the low influenza vaccination rates of Black Americans aged 18 and older in …

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …

The Effects Of External Focus Of Attention Exercise Rehabilitation On Dual Task Walking In Parkinson's Disease, Eric N. Beck

Theses and Dissertations (Comprehensive)

Parkinson’s disease impairs control of well-learned movements, and therefore, individuals with Parkinson’s disease are forced to walk with greater conscious control. This causes difficulties while walking and completing a secondary task simultaneously (dual tasking), in that distractions from conscious control of walking increase the risk of falls and injury. Although, attention-based exercise may be a potential avenue to decrease the demands associated with walking in Parkinson’s disease. For example, an external focus of attention (on manipulated objects) has been found to recruit the networks that are important for walking with little conscious control (automatic control networks). In contrast, an internal …

A Requirement For Y841 In Jak3 Enzymatic Activity And Hematopoietic Cancers, George Steven Martinez

Open Access Theses & Dissertations

A medical need exists for successfully treating people afflicted with leukemia, especially those who develop drug resistant forms. Relapse leukemia cases are particularly high within Hispanic populations where this disease is among the most frequently occurring cancer. Fourteen somatic mutations have been reported in Janus tyrosine kinase 3 (Jak3), including M511I and A573V, from patients with various forms of leukemia. To monitor drug sensitivity, a model system was developed. Indeed, many of these mutations have been shown to possess transforming ability in cell lines such as the IL-3 dependent pro-B cell line Ba/F3. As such, Ba/F3 cells were transformed to …

Determining The Role Of Poly [Adp-Ribose] Polymerase 1 (Parp-1) In Retroviral Infection, Luis Valdes Rodriguez

Open Access Theses & Dissertations

Possible links between PARP-1 and HIV-1 have been previously reported but the role of this protein during viral infection has remained elusive. Based on the high evolutionary conservation of PARP-1, from Drosophila to humans, we have been able to counteract the difficulties related with the functional redundancy manifested in the PARP family by studying the influence of PARP-1 on the expression of an endogenous retrovirus using the chicken B lymphoblastoid cell line DT40, this cell line exhibits low PARP-1 functional redundancy and is viable after PARP-1 knockout. We have determined that the transcription level of the endogenous retrovirus RAV-1 is …

Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared …

What Does Recent Neuroscience Tell Us About Criminal Responsibility?, Uri Maoz, Gideon Yaffe

Psychology Faculty Articles and Research

A defendant is criminally responsible for his action only if he is shown to have engaged in a guilty act—actus reus (eg for larceny, voluntarily taking someone else’s property without permission)—while possessing a guilty mind—mens rea (eg knowing that he had taken someone else’s property without permission, intending not to return it)—and lacking affirmative defenses (eg the insanity defense or self-defense). We therefore first review neuroscientific studies that bear on the nature of voluntary action, and so could, potentially, tell us something of importance about the actus reus of crimes.Then we look at studies of intention, perception of …

Ethnic Differences In Maternal Adipokines During Normal Pregnancy, Xinhua Chen, Theresa O Scholl

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Two adipokines (adiponectin and resistin) have opposite relations with insulin resistance and inflammation. Our major focus was to determine whether there were detectable ethnic differences in maternal adipokines during pregnancy. We also explored the correlation of the adipokines with maternal glucose homeostasis, blood pressure and anthropometric parameters. Pregnant women (n = 1634) were from a large prospective cohort study in Camden NJ (African-American 36.8%; Hispanic 47.6%; Caucasian 15.6%). Serum adiponectin and resistin were measured at entry (week 16.8) and the 3rd trimester (week 30.7) using the Luminex xMapTechnology. Significant differences were observed among ethnic groups, controlling for confounding variables. African …

The Effect Of Body Mass Index On Graft Function And Kidney Transplant Outcomes, Morgan Galle

Theses & Dissertations

Background: When determining eligibility for kidney transplantation, body mass index (BMI) is often a debatable criterion for transplant due to the clinical indication, an elevated BMI has adverse effects on kidney transplant outcomes. There is a current gap in research on the effect BMI has on kidney transplant outcomes.

Purpose: The purpose of this study was to determine the role BMI plays in post-kidney transplant clinical outcomes including delayed graft function, new onset diabetes after transplant, wound complications, hospital length of stay, albumin, and readmissions to the hospital from initial hospitalization and at six months following kidney transplantation. The primary …

Regulatory Roles Of Mical-L1 And Ehd1 In Cell Signaling And Mitosis, James B. Reinecke

Theses & Dissertations

Membrane trafficking is a basic cell biological process that controls the distribution of proteins and lipids. Our lab is particularly interested in delineating the cellular functions as well as the molecular mechanisms that regulate the C-terminal Eps15 Homology Domain (EHD) protein family of adenosine-5’-triphosphatases in mammalian cells. EHD1-4 are ubiquitously expressed in mammalian tissues and serve partially overlapping but also distinct functions in regulating membrane shaping and fission along the endocytic pathway. Specifically, EHD1 is recruited to tubular recycling endosomes (TREs) by Molecule Interacting with CasL Like-1 (MICAL-L1) and facilitates TRE fission and release of cargo from the perinuclear endocytic …

The Feedforward And Feedback Controls On Gait In Adults With Diabetes, Chun-Kai Huang

Theses & Dissertations

There are nearly 26 million people with diabetes mellitus (DM) in the US, and half of chronic DMs develop somatosensory deficits due to diabetic polyneuropathy or diabetic peripheral neuropathy (DPN). The absence or impaired somatosensory feedback (e.g. touch sensation or joint proprioception) resulted from the damage of large nerve fiber, and motor deficits such as attenuated muscle strength and abnormal plantar pressure of lower extremity have been identified in DPN, and these sensorimotor impairments lead to an increased number of falls. To reduce the risk of falling, a well-coordinated and adapted limb movement driven by the feedforward (anticipatory) and feedback …

Finding Optimal Brain Mappings Using Integer Linear Programming Solvers And Other Methods, Heriberto Flores

Honors Theses

No abstract provided.

The Incidence Of Early Stage Postoperative Nausea And Vomiting Following The Use Of Nitrous Oxide And Prophylactic Antiemetic Therapy: Implications For Clinical Practice, James Sullivan

Doctoral Projects

Nitrous oxide (N₂O) is a volatile agent currently used during the induction and maintenance of general anesthesia. Since it’s discovery in 1786 by Dr. Priestly, it is the oldest volatile agent to find continued use in current practice (Kossick, 2014). In conjunction with its extensive history is the debate regarding its emetic properties. Numerous studies have investigated the effect of nitrous oxide to produce postoperative nausea and vomiting (PONV) with varying and often conflicting results. Generally speaking, nitrous oxide is theoretically an emetic and is believed to be associated with PONV (Tramer, Moore, & McQuay, 1996). This has …

Recommendations For The Development Of New Hospital Guidelines Due To The Effects Of Antibiotics On Clostridium Difficile Colitis, Megan Kohsel

Honors Theses

Clostridium difficile colitis is an infection that causes inflammation of the colon and diarrhea. This can even lead to death in some cases. The incidence of this infection and its overall effects have been on the rise throughout the last twenty years as antibiotics have been prescribed more frequently. Therefore, it is necessary that the rate of C. difficile infection is lowered by improved guidelines for hospitals, so that fewer people are infected and also that fewer antibiotics are prescribed to avoid the infection with C. difficle.

Role Of Maternal Dietary Peanut Exposure In Development Of Food Allergy And Oral Tolerance, Magdia De Jesus

Biomedical Sciences Faculty Scholarship

Background The impact of maternal ingestion of peanut during pregnancy and lactation on an offspring’s risk for peanut allergy is under debate. Objective To investigate the influence of maternal dietary peanut exposure and breast milk on an offspring’s allergy risk. Methods Preconceptionally peanut-exposed C3H/HeJ females were either fed or not fed peanut during pregnancy and lactation. The offsprings’ responses to peanut sensitization or oral tolerance induction by feeding antigen prior to immunization were assessed. We also assessed the impact of immune murine milk on tolerance induction pre- or post-weaning. For antigen uptake studies, mice were gavaged with fluorescent peanut in …

Interaction Of Alu Polymorphisms And Novel Measures Of Discrimination In Association With Blood Pressure In African Americans Living In Tallahassee, Alexis C. Boulter, Jackyn Quinlan, Aida T. Miró-Herrans, Laurel N. Pearson, Nubiana L. Todd, Clarence C. Gravlee, Connie J. Mulligan

Human Biology Open Access Pre-Prints

African Americans are 40% more likely to be afflicted with hypertension in comparison to non-Hispanic, white Americans, resulting in a 30% higher instance of mortality due to cardiovascular disease. There is debate about the relative contributions of genetic and sociocultural risk factors to the racial disparity in hypertension.

We assayed three Alu insertion polymorphisms located in the angiotensin-1-converting enzyme (ACE), tissue plasminogen activator (PLAT), and with no-lysine kinase 1 (WNK1) genes. We also estimated West African genetic ancestry and developed novel measures of perceived discrimination to create a biocultural model of blood pressure among …

The Development Of A Platform For Expression And Purification Of The Mammalian Transmembrane Transporter Abca4, Amaryllis Ortiz

Graduate School of Biomedical Sciences Theses and Dissertations

Purpose- ABCA4 is an ATP Binding Cassette (ABC) protein localized at cone and rod photoreceptor outer segments of the retina. Though mutations in ABCA4 have been found to cause a broad spectrum of disorders, ABCA4's high molecular weight (~210 kDa) and biochemical transmembrane properties have made ABCA4 functional studies unsuccessful. Identifying how ABCA4 functions might have significant clinical impact and open unanticipated avenues for therapeutic interventions. Thus, the objective of this study was to develop a new expression system able to produce the full-length, correctly folded and fully functional ABCA4 protein.

Methods- the ABCA4 gene was amplified from the PCMV6-ABCA4 …

Cardiovascular Regulation And Effects Of Respiratory Motor Training In Patients With Chronic Spinal Cord Injury., Bonnie Legg Ditterline

Electronic Theses and Dissertations

This dissertation attempts to discover the mechanisms between cardiovascular and respiratory motor control post spinal cord injury (SCI): in normal, non-injured (NI) persons, cardiovascular regulation is dependent upon respiration, but there is nothing that suggests the mechanism for this relationship post-SCI. Thus we hoped to evaluate various aspects of cardiovascular regulation to further illustrate how this relationship is changed or unchanged by SCI. Chapter I describes the anatomy and physiology of the spine, respiratory system, and cardiovascular system in a NI person, and then describes how the function of these systems is changed by SCI. In addition, we describe therapies …

Role Of B Cell Receptor Signaling In Il-10 Production By Normal And Malignant B-1 Cells., Sara S Alhakeem, Vishal J Sindhava, Mary K Mckenna, Beth W Gachuki, John C Byrd, Natarajan Muthusamy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells are considered innate immune cells, which produce the majority of natural antibodies. B-1 cell responses to B cell receptor (BCR) and Toll-like receptor ligation are tightly regulated owing to the cross-reactivity to self-antigens. CD5 has been shown to play a major role in downregulation of BCR responses in B-1 cells. Here, we provide evidence for another mechanism by which BCR response is regulated in B-1 cells. B-1 cells, as well as their malignant counterpart, B cell chronic lymphocytic leukemia (B-CLL) cells, produce interleukin-10 (IL-10) constitutively. IL-10 secretion by normal B-1 cells downregulates their proliferation responses to BCR ligation. …

Investigation Of Quatitative Image Features From Pretreatment Ct And Fdg-Pet Scans In Stage Iii Nsclc Patients Undergoing Defintive Radiation Therapy, David Fried

Dissertations and Theses (Open Access)

The purpose of this work was to determine if quantitative image features (QIFs) extracted from computed tomography (CT) and flourodeoxyglucose (FDG) positron emission tomography (PET) could provide prognostic information to improve outcome models. Our goal for this work was to determine if it may one day be feasible to incorporate QIFs into personalized cancer care. QIFs were used to quantitatively characterize patient disease as seen on imaging. A leave-one-out cross-validation procedure was used to assess the prognostic ability of QIFs extracted from CT and PET in addition to conventional prognostic factors (CPFs). QIFs were found to improve model fit for …