Digital Commons Network^™

Dynamic Reciprocity Between Cells And Their Microenvironment In Reproduction, J. T. Thorne, T. R. Segal, S. Chang, S. Jorge, J. H. Segars, P. C. Leppert

Journal Articles

Dynamic reciprocity (DR) refers to the ongoing, bidirectional interaction between cells and their microenvironment, specifically the extracellular matrix (ECM). The continuous remodeling of the ECM exerts mechanical force on cells and modifies biochemical mediators near the cell membrane, thereby initiating cell-signaling cascades that produce changes in gene expression and cell behavior. Cellular changes, in turn, affect the composition and organization of ECM components. These continuous interactions are the fundamental principle behind DR, and its critical role throughout development and adult tissue homeostasis has been extensively investigated. While DR in the mammary gland has been well described, we provide direct evidence …

Egfr And Her2: Is There A Role In Ovarian Cancer?, E. Teplinsky, F. Muggia

Journal Articles

Advanced ovarian cancer carries a grim prognosis and development of targeted therapies to improve outcomes has become an active area of research in this disease. The epidermal growth factor receptor (EGFR) and HER2/neu have shown to be overexpressed in ovarian cancer and there have been several clinical trials evaluating anti-EGFR and HER2 therapies in ovarian cancer. Unfortunately, the drugs have shown minimal efficacy and more recent work has now focused on identifying mechanisms of resistance and alternative ways of targeting these pathways. This review will discuss the currently published trials with anti-EGFR and HER2 agents in ovarian cancer and the …

Prenatal Nutrition Counseling Designed To Reduce The Intake Of Moderate And High Glycemic Index Foods Among Selected Normal, Overweight, And Obese Patients From A Nonprofit Faith-Based Patient Medical Care Home, Debra T. Gogatz

Regis University Student Publications (comprehensive collection)

Executive Summary

Prenatal Nutrition Counseling Designed to Reduce the Intake of Moderate and High Glycemic Index Foods Among Selected Normal, Overweight, and Obese Patients from a Nonprofit Faith-based Patient Medical Care Home

Problem

Minority and economically disadvantaged clients at a faith based nonprofit patient medical care home were identified as needing dietary counseling in the first trimester of pregnancy. There has existed a preponderance of evidence linking excessive weight gain in pregnancy to multiple complications for mother and child with a suggested relationship specific to the inflammatory processed initiated within the human body related to the ingestion of excessive calories …

Antidiarrheal And Antispasmodic Activities Of Adiantum Capillus-Veneris Are Predominantly Mediated Through Atp-Dependent K+ Channels Activation, Khalid Hussain Janbaz, Waseem Hassan, Hassan Mehmood, Anwar Hassan Gilani

Department of Biological & Biomedical Sciences

The study was tempted to explore the scientific basis for the medicinal use of Adiantum capillus-veneris L. in diarrhea using the in vivo and in vitro assays. The crude extract of dried leaves of A. capillus-veneris exhibited antidiarrheal effect against castor oil-induced diarrhea in mice at 300 and 500 mg/kg, similar to the effect loperamide. It was also found safe up to administered dose of 7 g/kg in mice. In isolated rabbit jejunum, extract of A. capillus-veneris showed a concentration-dependent relaxation of spontaneous and low K⁺ (25 mM)-induced contractions and had weak inhibitory effect on high K⁺ (80 …

The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]Pyrimidine Antifolates", Shermaine Kimberly Mitchell-Ryan

Wayne State University Dissertations

Ovarian Cancer is the fifth leading cause of cancer-related death of women in the United States. Epithelial Ovarian Cancer (EOC) constitutes 85-90% of malignancies within the ovary, with an alarming majority of these cases diagnosed at advanced stage. While most patients are initially highly responsive to the current treatment standard, there is a very high probability that they will recur with a drug resistant fatal disease. Currently there is no validated comprehensive model of disease progression for ovarian cancer, although tremendous progress has been made in understanding the origin of this disease and a putative precursor lesion has been identified …

The Effects Of Landscape On Malaria Vectors Of The Neotropics, William David Lainhart

Legacy Theses & Dissertations (2009 - 2024)

Worldwide malaria control efforts have had varying degrees of success, leaving many countries either eliminating malaria or controlling malaria. In order to maintain forward momentum toward malaria elimination, malaria-eliminating and –controlling countries require different information regarding risk factors, spatial distributions of cases and vectors, vector biology metrics, and vector population genetics. The goal of this dissertation work was to provide information that addresses the knowledge gaps preventing the creation of effective vector and malaria control programs in one malaria-eliminating country (Panama) and two malaria-controlling countries (Peru and Brazil). Case data from Panama were analyzed to assess differences in risk factors …

Investigating The Role Of Myristoylated Alanine Rich C Kinase Substrate's (Marcks's) Effector Domain In Lung And Brain Cancer Biology, Timothy D. Rohrbach

All ETDs from UAB

In this study, we investigated the role MARCKS's Effector Domain plays in lung and brain cancer biology. Initially, we identified that MARCKS was present in a range of lung cancer histologies including: squamous cell, adenocarcinoma, and normal lung tissues among others. In addition, lung adenocarcinoma patients with a mutation in the MARCKS gene correlated with decreased survival as determined by The Cancer Genome Atlas. In vitro studies identified that the phosphorylation status of MARCKS's Effector Domain was able to influence lung cancer radiation sensitivity. When MARCKS's Effector Domain was in a non-phosphorylated state, A549 lung cancer cell lines experienced increased …

Histomorphometric And Fractal Analysis Of Femoral, Tibial, And Metatarsal Compact Bone Samples In Sheep (Ovis Aries), Goat (Capra Hircus), And Roe Deer (Capreolus Capreolus), Alexandru Gudea, Andrei Stefan

Turkish Journal of Veterinary & Animal Sciences

Histological sections of femur, tibia, and metatarsals originating from sheep (Ovis aries), goat (Capra hircus), and roe deer (Capreolus capreolus) were examined in this study. Our research focused mainly on the quantitative characteristics of the microstructure of these bones. The areas, perimeters, minimum and maximum diameters of the secondary Haversian units, as well as structures of the primary osteonal units were assessed using comparative statistical methods. In addition to these parameters, the present paper investigated the usefulness of fractal analysis (fractal dimension and lacunarity), a new approach that quantifies the complexity and the emptiness pattern of biological structures. Moreover, our …

Interpersonal Safety Of Active Duty Women In The Deployed Environment Of Bagram Afghanistan, Cynthia Tara Ferguson

Walden Dissertations and Doctoral Studies

In the United States Armed Forces, 30% of women in the military suffer physical assault each year; in 2009, there were 22 reported cases of sexual assault in the U.S. Central Command. Aggravated assault, gang violence, sexual assault, homicide, and suicide can damage the morale of military personnel at a deployed site and collectively cost millions of dollars over time. Interpersonal violence in the United States military is destructive to the military system and directly diminishes mission readiness. This study was designed to illuminate the environmental, cultural, and political influences that affect interpersonal safety among military women in the deployed …

Influence Of Maternal Prior Life Adversity On The Psycho-Neuroendocrine-Immune Profile During Pregnancy, Karen J. Kotz

Dissertations

Pregnancy is accompanied by a multitude of physical and psychological changes. Adaptation to these changes through reduced anxiety and attenuated stress responsiveness is necessary across gestation and into the postpartum period for optimal maternal-infant health. In contrast, exposure to higher amounts of stressors during pregnancy can disrupt neuroendocrine-immune processes required for successful pregnancy outcomes. Evolving evidence demonstrates that exposure to adversity early in life has long-lasting effects on stress response systems that alter stress reactivity during adulthood. Given this evidence, it is posited that women who experience greater pre-pregnancy adversity during their childhood are at greater risk for negative maternal-infant …

Health Assessment For Loved Ones: Development And Validation Of A New Instrument To Measure Well-Being In Military Spouses, Christi Luby

Open Access Theses & Dissertations

Since 2001, over 2.7 million US troops have deployed in support of the ongoing conflicts in the Middle East. Combat stress and deployments affect Service members, and consequently affect their spouses/intimate partners. In addition, these spouses often act as the social support system to other spouses experiencing traumatic events, such as death, injury, or illness of their deployed soldier. These indirect exposures to trauma may make spouses vulnerable; yet little research has focused on how the lived experiences of spouses of deployed and returning US Service members have affected their well-being. The purpose of this three-part study was to develop …

Genetic And Chemical Dissection Of Bloodbrain Barrier Development In Zebrafish, Robyn Anne Umans

Theses and Dissertations (ETD)

The blood-brain barrier (BBB) maintains a homeostatic environment as well as prohibits the entrance of xenobiotics into the brain. Because of these qualities, drug delivery is a fundamental challenge for the treatment of many diseases of the central nervous system (CNS). Along with limiting the access of therapeutics into the brain, the BBB is also impaired in CNS pathologies. Understanding the molecular cues that are essential for healthy BBB development and integrity may reveal targets for drug delivery leading to decreased progression or possible treatment of many detrimental CNS diseases. While the central features of the BBB have been accepted, …

Computer-Aided Drug Design And Discovery, Screening And Synthesis Of Small Molecule Inhibitors Of Nucleoside Transporters, Hilaire Colleen Playa

Theses and Dissertations (ETD)

Using prior biological data, pharmacophore models were made for hCNT1, hCNT3, hENT1, and hENT4. The hCNT3 and hCNT1 pharmacophore were used to select compounds for biological testing. The NBMPR analogue and dipyridamole analogue hENT1 pharmacophores were compared to each other and to a combined pharmacophore for hENT1. The dipyridamole analogue pharmacophore better predicted non-nucleoside small molecule inhibitors, and as such appears to be the better tool for aiding in the design of new small molecule inhibitors. The hCNT3 pharmacophore failed to select active compounds and as such must be redesigned. The hCNT1 pharmacophore succeeded in identifying two moderately active compounds …

Caspase-3 Mediates The Pathogenic Effect Of Yersinia Pestis Yopm In Liver Of C57bl/6 Mice And Contributes To Yopm's Function In Spleen, Zhan Ye, Amanda A. Gorman, Annette M. Uittenbogaard, Tanya Myers-Morales, Alan M. Kaplan, Donald A. Cohen, Susan C. Straley

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found …

Tps Mutational Status Is A Potential Marker For Risk Stratification In Wilms Tumour With Diffuse Anaplasia, Mariana Maschietto, Richard D. Williams, Tasnim Chagtai, Sergey D. Popov, Neil J. Sebire, Gordan Vujanic, Elizabeth Perlman, James R. Anderson, Paul Grundy, Jeffrey S. Dome, Kathy Pritchard-Jones

Pediatrics Faculty Publications

Purpose

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whetherTP53 mutational status confers additional prognostic information.

Patients and Methods

We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. …

Mapping Regions Of Rnf168 Required For Its Degradation By Icp0, Andrea Cyr, Matthew Weitzman

e-Research: A Journal of Undergraduate Work

Viruses establish infection by overtaking host cell processes and developing mechanisms that promote viral replication. Herpes simplex virus undergoes lytic and latent cycles of infection throughout the lifespan of its host. The viral genome is transcriptionally silent during latency, but viral proteins are produced upon reactivation. Herpes simplex virus type 1 encodes the ICP0 protein, an E3 ubiquitin ligase required for reactivation from latency of the infectious virus. The immediate-early protein ICP0 regulates the herpes simplex virus by activating viral gene expression thereby initiating lytic infection. Cellular proteins are degraded by ICP0, promoting the virus to enter the lytic cycle. …

Nuclear And Mitochondrial Trna-Lookalikes In The Human Genome., Aristeidis G Telonis, Phillipe Loher, Yohei Kirino, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

We are interested in identifying and characterizing loci of the human genome that harbor sequences resembling known mitochondrial and nuclear tRNAs. To this end, we used the known nuclear and mitochondrial tRNA genes (the "tRNA-Reference" set) to search for "tRNA-lookalikes" and found many such loci at different levels of sequence conservation. We find that the large majority of these tRNA-lookalikes resemble mitochondrial tRNAs and exhibit a skewed over-representation in favor of some mitochondrial anticodons. Our analysis shows that the tRNA-lookalikes have infiltrated specific chromosomes and are preferentially located in close proximity to known nuclear tRNAs (z-score ≤ -2.54, P-value ≤ …

Epoxide-Mediated Differential Packaging Of Cif And Other Virulence Factors Into Outer Membrane Vesicles, A. E. Ballok, L. M. Filkins, J.. M. Bomberger, B. A. Stanton, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa produces outer membrane vesicles (OMVs) that contain a number of secreted bacterial proteins, including phospholipases, alkaline phosphatase, and the CFTR inhibitory factor (Cif). Previously, Cif, an epoxide hydrolase, was shown to be regulated at the transcriptional level by epoxides, which serve as ligands of the repressor, CifR. Here, we tested whether epoxides have an effect on Cif levels in OMVs. We showed that growth of P. aeruginosa in the presence of specific epoxi

Synthesis And Biological Study Of Adenylyl Cyclase Inhibitors, Siyuan Sun, Zhishi Ye, Mingji Dai

The Summer Undergraduate Research Fellowship (SURF) Symposium

Adenylyl cyclases (AC) is a critical family of enzymes which modulates the dynamic cellular level of cAMP, cyclic adenosine monophosphate. The study of cAMP showed that it is indispensable for the signal transduction cascades during many physiological processes, such as immune responses and metabolism which highly relate to cancers. Previous studies of AC inhibitors have been limited due to a lack of isoform-selective small molecule modulators. Selectivity of the molecules is imperative to the activation of only the desired AC inhibitor. The design of the described project was to test the structure activity relationship (SAR) by synthesizing a class of …

Stochastic Data Assimilation Approaches For Magnetic Resonance Temperature Imaging, Joshua P. Yung

Dissertations and Theses (Open Access)

During magnetic resonance (MR)-guided thermal therapies, proton resonance frequency shift (PRFS) based MR temperature imaging can quantitatively monitor tissue temperature changes. It is widely known that the PRFS technique is easily perturbed by tissue motion, tissue susceptibility changes, magnetic field drift, and modality–dependent applicator induced artifacts. Due to recent advances in computational algorithms and hardware, much more powerful statistical analysis methods are becoming realizable in the real-time processing environment. To this end, my dissertation research focused on the development, validation, and implementation of stochastic data-driven processing techniques to increase the robustness of MR temperature monitoring during thermal therapies. MR temperature …

Molecular And Functional Identification Of A Mitochondrial Ryanodine Receptor In Neurons., Regina Jakob, Gisela Beutner, Virendra K Sharma, Yuntao Duan, Robert A Gross, Stephen Hurst, Bong Sook Jhun, Jin O-Uchi, Shey-Shing Sheu

Department of Medicine Faculty Papers

Mitochondrial Ca(2+) controls numerous cell functions, such as energy metabolism, reactive oxygen species generation, spatiotemporal dynamics of Ca(2+) signaling, cell growth and death in various cell types including neurons. Mitochondrial Ca(2+) accumulation is mainly mediated by the mitochondrial Ca(2+) uniporter (MCU), but recent reports also indicate that mitochondrial Ca(2+)-influx mechanisms are regulated not only by MCU, but also by multiple channels/transporters. We previously reported that ryanodine receptor (RyR), which is a one of the main Ca(2+)-release channels at endoplasmic/sarcoplasmic reticulum (SR/ER) in excitable cells, is expressed at the mitochondrial inner membrane (IMM) and serves as a part of the Ca(2+) …

A Grounded Theory Of Suicidality In Children Ten And Younger, Katherine Angela Heimsch

Counseling & Human Services Theses & Dissertations

Once every two days in the United States, a child aged 5 to 14 years old dies by suicide (World Health Organization, 2010). When viewed on a spectrum that includes suicidal ideation, verbalizations, behaviors, and attempts, the problem of youth suicidality is actually far greater than the numbers of completed suicides suggest (Cheng, Tao, Riley, Kann, Ye, Tian...Hu, 2009). This study examined suicidality in children ages 10 and younger, and included the characteristics of suicidal children, factors that influence childhood suicidality, and treatment implications. The researcher conducted 12 semi-structured qualitative interviews with experienced treatment providers and performed a content analysis …

An Evaluation Of The East Indianapolis Food Desert, Angelina Qin

Undergraduate Honors Thesis Collection

The Indy East Food Desert (IEFD) appears to suffer from many common conditions noted by various scholars as food desert identifiers. Yet, its situation still remains unique. Though there is a prevalence of minority populations, low-income households, and low-education attainment levels, there are also factors of low-access, poor food options (within the limited food outlets in the neighborhoods), and poor eating habits which shape the situation of the community. In an attempt to alleviate the food desert problems, the Indy East Food Desert Coalition (IEFDC) was formed. IEFDC partnered with Butler University's Center for Urban Ecology in order to assess …

Studies On Rationally Designed, Allosteric, Coagulation Inhibitors, Rio Boothello

Theses and Dissertations

Heparin is a natural allosteric modulator, with numerous structural and conformational variations leading to many reports of bleeding complications and variations in anticoagulant effects. A flurry of research has been directed towards understanding this puzzle. This work entails the utilization of three unique strategies to further our understanding of this complex issue. Traditional synthetic, biosynthetic and biophysical approaches have failed to conquer the GAG-protein complexity. Computational analysis however could serve as a powerful approach to decipher this dilemma. A dual filter algorithm was incorporated to identify unique hexasaccharide sequences for HCII and AT. Our experimental studies exhibit a good correlation …

The Dna Methylome And Transcriptome Of Different Brain Regions In Schizophrenia And Bipolar Disorder, Yun Xiao, Cynthia Camarillo, Yanyan Ping, Tania Bedard Arana, Hongying Zhao, Peter M. Thompson, Chaohan Xu, Brenda Su, Michael A. Escamilla, Chunxiang Mao, Chun Xu

Health & Biomedical Sciences Faculty Publications

Extensive changes in DNA methylation have been observed in schizophrenia (SC) and bipolar disorder (BP), and may contribute to the pathogenesis of these disorders. Here, we performed genome-scale DNA methylation profiling using methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) on two brain regions (including frontal cortex and anterior cingulate) in 5 SC, 7 BP and 6 normal subjects. Comparing with normal controls, we identified substantial differentially methylated regions (DMRs) in these two brain regions of SC and BP. To our surprise, different brain regions show completely distinct distributions of DMRs across the genomes. In frontal cortex of both SC and …

The End Of Alzheimer's Disease - From Biochemical Pharmacology To Ecopsychosociology: A Personal Perspective, Peter J. Whitehouse

Faculty Scholarship

The future of the Alzheimer's disease (AD) field involves a more complete understanding not only the state of current scientific approaches, but also the linguistic and cultural context of preclinical and clinical research and policy activities. The challenges surrounding dementia are large and growing but are only part of broader social and health concerns. In this latter context, the current state of research in the AD area is reviewed together with necessary priorities in moving forward. Creating a more optimistic future will depend less on genetic and reductionist approaches and more on environmental and intergenerative approaches that will aid in …

Current Pathophysiological Concepts In Cerebral Small Vessel Disease., Fred Rincon, Clinton B Wright

Department of Neurology Faculty Papers

The association between cerebral small vessel disease (SVD) - in the form of white matter lesions, infarctions, and hemorrhages - with vascular cognitive impairment (VCI), has mostly been deduced from observational studies. Pathological conditions affecting the small vessels of the brain and leading to SVD have suggested plausible molecular mechanisms involved in vascular damage and their impact on brain function. However, much still needs to be clarified in understanding the pathophysiology of VCI, the role of neurodegenerative processes such as Alzheimer's disease, and the impact of aging itself. In addition, both genetic predispositions and environmental exposures may potentiate the development …

Strad Pseudokinases Regulate Axogenesis And Lkb1 Stability, Biliana O. Veleva-Rotse, James L. Smart, Annette F. Baas, Benjamin Edmonds, Zi-Ming Zhao, Allyson Brown, Lillian R. Klug, Kelly Hansen, Gabrielle Rielly, Alexandria P. Gardner, Krishnaveni Subbiah, Eric A. Gaucher, Hans Clevers, Anthony P. Barnes

Faculty Publications - Department of Biological & Molecular Science

No abstract provided.

Perspectives Of Social Work Students On Nutrition And The Nutrition Effects On Mental Health, Diana Tran

Electronic Theses, Projects, and Dissertations

Nutrition is related to the mental well-being of clients. However, the nutritional views and practices of social workers in the mental health field have not been thoroughly explored. By using the post-positivist paradigm, 15 mental health social work students were interviewed for their perspectives regarding nutrition and nutrition’s effect on stress. Their main ideas were identified, connected, and organized to develop a theoretical statement. The resulting theory focused on the development of social work students' perspectives in applying nutrition into their mental health practice. The students were influenced by a variety of background factors, including their education, barriers to applying …

Repair Of Oxidative Dna Damage And Cancer: Recent Progress In Dna Base Excision Repair, Timothy L. Scott, Suganya Rangaswamy, Christina A. Wicker, Tadahide Izumi

Toxicology and Cancer Biology Faculty Publications

SIGNIFICANCE: Reactive oxygen species (ROS) are generated by exogenous and environmental genotoxins, but also arise from mitochondria as byproducts of respiration in the body. ROS generate DNA damage of which pathological consequence, including cancer is well established. Research efforts are intense to understand the mechanism of DNA base excision repair, the primary mechanism to protect cells from genotoxicity caused by ROS.

RECENT ADVANCES: In addition to the notion that oxidative DNA damage causes transformation of cells, recent studies have revealed how the mitochondrial deficiencies and ROS generation alter cell growth during the cancer transformation.

CRITICAL ISSUES: The emphasis of this …