Medical Sciences Commons^™

Neuropsychological Outcome In Relation To Duration Of Early Orphanage Experience, Jacquelyn Marie Perry Avery

Wayne State University Dissertations

In this sample of 144 children with a history of prior orphanage experience, increasing duration of institutionalization is related to decreasing performance for a number of cognitive domains, most consistently verbal measures and executive Functioning measures. The relationships with duration for measures requiring visual-spatial skills were more mixed and a visual reasoning task was found to significantly relate to duration but not a measure of visual memory or a measure of nonverbal achievement. There was little evidence to support a relationship between the duration of institutionalization and fine-motor dexterity. The strongest relationships with duration were observed for language measures followed …

Multi-Modality Assessment Of Language Function, Erik Carmen Brown

Wayne State University Dissertations

The work presented as part of this dissertation represents a multi-modality study of language structure and function. The primary functional modality employed is task-related electrocorticography (ECoG). This is complemented by discussion and evaluation of previously published functional magnetic resonance imaging (fMRI) data. Language-related structure is explored using diffusion-weighted magnetic resonance imaging in conjunction with ECoG data. The scientific questions pursued are broad and include reevaluation of previously proposed theories.

We start by taking the first steps in validating our naming-related ECoG approach by comparing our results from a small cohort of patients to the clinical gold-standard technique of electrical brain …

Striatal Dopamine Dynamics Upon Manganese Accumulation, Madiha Khalid

Wayne State University Dissertations

STRIATAL DOPAMINE DYNAMICS UPON MANGANESE ACCUMULATION

by MADIHA KHALID

August 2013

Advisor: Dr. Tiffany Mathews

Major: Chemistry (Analytical)

Degree: Doctor of Philosophy

Although manganese (Mn) is fundamental for many biological processes, exposure to excess amounts leads to a neurological disorder termed manganism. Due to its symptomatic similarity to Parkinson's disease, as well its preferential accumulation in dopamine rich brain regions, alterations in the dopamine system are implicated in the onset of manganism. In my research, Mn overexposure is mimicked via subcutaneous administration of manganese chloride to C57BL/6 mice over the course of seven days using a protocol that has been …

White Matter Integrity And Age Related Differences In Reaction Time Components, Yiqin Yang

Wayne State University Dissertations

Reduced speed in information processing is a well-documented phenomenon associated with advanced aging. Age-related deterioration in white matter integrity might play a role in age-related increase in reaction time (RT). However, the association between microstructural differences in particular white matter regions or tracts with RT is unclear. Decomposing RT into parts might be a better way to understand the relationship due to multiple processes involved in RT. In a lifespan sample of 90 healthy normotensive participants, this study examined the association between RT components derived from the Ratcliff diffusion model with age related difference in DTI indices of a wide …

Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-β1-induced NSCLC cells that are reminiscent of EMT cells.

Methods

Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled …

The Influence Of Gender And Aging On The Neural Circuitry Supporing Facial Emotion Processing In Adults With Major Depressive Disorder, Emily Briceno

Wayne State University Dissertations

Major Depressive Disorder (MDD) is associated with decrements in facial emotion processing (FEP). Previous studies investigating the neural substrates of these decrements have often reported hyperactivity of emotion processing circuitry. Neural circuitry supporting FEP has been shown to be different between healthy men and women, and between young and elder adults. However, no prior studies have investigated how gender and aging affect emotion processing circuitry in individuals with MDD. The present study aimed to investigate the influence of gender and aging on emotion processing circuitry in MDD. One hundred-ten adults, grouped into subgroups according to MDD status, gender, and age …

Endometriosis Of The Lung: Report Of A Case And Literature Review, Haidong Huang, Chen Li, Paul Zarogoulidis, Kaid Darwiche, Nikolaos Machairiotis, Lixin Yang, Michael Simoff, Eduardo Celis, Tiejun Zhao, Konstantinos Zarogoulidis, Nikolaos Katsikogiannis, Wolfgang Hohenforst-Schmidt, Qiang Li

Wayne State University Associated BioMed Central Scholarship

Abstract

This paper reports a case of endometriosis of the lung in a 29-year-old woman with long-term periodic catamenial hemoptysis. A chest computed tomography image obtained during menstruation revealed a radiographic opaque lesion in the lingular segment of the left superior lobe. During bronchoscopy, bleeding in the mucosa of the distal bronchus of the lingular segment of the left superior lobe was observed. Histopathology subsequent to an exploratory thoracotomy confirmed the diagnosis of endometriosis of the left lung. The 2-year follow-up after lingular lobectomy of the left superior lobe showed no recurrence or complications.

Decreased Neuroinflammation And Increased Brain Energy Homeostasis Following Environmental Enrichment After Mild Traumatic Brain Injury Is Associated With Improvement In Cognitive Function, Teresita L. Briones, Julie Woods, Magdalena Rogozinska

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Persistent neuroinflammation and disruptions in brain energy metabolism is commonly seen in traumatic brain injury (TBI). Because of the lack of success of most TBI interventions and the documented benefits of environmental enrichment (EE) in enhancing brain plasticity, here we focused our study on use of EE in regulating injury-induced neuroinflammation and disruptions in energy metabolism in the prefrontal cortex and hippocampus. Adult male Wistar rats were used in the study and randomly assigned to receive either: mild TBI (mTBI) using the controlled cortical injury model or sham surgery. Following surgery, rats from each group were further randomized …

Hyperglycemia Induces Differential Change In Oxidative Stress At Gene Expression And Functional Levels In Huvec And Hmvec, Hemang Patel, Juan Chen, Kumuda C. Das, Mahendra Kavdia

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Endothelial dysfunction precedes pathogenesis of vascular complications in diabetes. In recent years, the mechanisms of endothelial dysfunction were investigated to outline strategies for its treatment. However, the therapies for dysfunctional endothelium resulted in multiple clinical trial failures and remain elusive. There is a need for defining hyperglycemia-induced endothelial dysfunction with both generic and specific dysfunctional changes in endothelial cells (EC) using a systems approach. In this study, we investigated hyperglycemia-induced endothelial dysfunction in HUVEC and HMVEC. We investigated hyperglycemia-induced functional changes (superoxide (O₂‾), and hydrogen peroxide (H₂O₂) production and mitochondrial membrane polarization) …

Studies Of Regulated Exocytosis From Neuroendocrine Cells, Madhurima Das

Wayne State University Theses

In this thesis we study cargo release and fusion pore dilation during calcium triggered exocytosis and the co-localization of calcium sensing proteins essential for exocytosis, in neuroendocrine cells.

Pancreatic beta cells secrete several hormones, the most studied one being insulin. C-peptide is a protein which is co-stored with and secreted from the same vesicles as insulin. It is found in the soluble phase unlike insulin, which is found in the dense core. The pancreatic beta cells also secrete the Chromogranin B (CgB) which is mostly found in the dense cores of secretory vesicles. In chapter 1, we found that CgB, …

Progress Towards Understanding Of Mechanisms Of Action Of Potent Multifunctional Disease Modifying Therapeutics For Parkinson's Disease & Investigating The Methamphetamine-Induced Striatal Microglia Activation., Mrudang M. Shah

Wayne State University Dissertations

PROGRESS TOWARDS UNDERSTANDING OF MECHANISMS OF ACTION OF POTENT MULTIFUNCTIONAL DISEASE MODIFYING

THERAPEUTICS FOR PARKINSON'S DISEASE.

by

MRUDANG MANOJKUMAR SHAH

December 2013

Advisor: Dr. Aloke Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Our long term goal is to design and develop potent multifunctional disease modifying therapeutics for Parkinson's disease. The objective of my dissertation was to understand the mechanisms of action of some potent small molecules (synthesized in our lab) as a disease modifying Parkinson's disease therapeutic. The objective was achieved by pursuing the following two specific aims:

1. Investigating anti-oxidant and neuroprotective effects of a lead molecule (D-512) …

The Incidence And Aetiology Of Hospitalised Community-Acquired Pneumonia Among Vietnamese Adults: A Prospective Surveillance In Central Vietnam, Kensuke Takahashi, Motoi Suzuki, Le Minh, Nguyen Anh, Luu Thi Huong, Tran Vo Son, Phan Long, Nguyen Thi Ai, Le Tho, Konosuke Morimoto, Paul E. Kilgore, Dang Anh, Koya Ariyoshi, Lay Yoshida

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lower respiratory tract infection (LRTI) including Community-acquired pneumonia (CAP) is a common infectious disease that is associated with significant morbidity and mortality. The patterns of aetiological pathogens differ by region and country. Special attention must be paid to CAP in Southeast Asia (SEA), a region facing rapid demographic transition. Estimates burden and aetiological patterns of CAP are essential for the clinical and public health management. The purposes of the study are to determine the incidence, aetiological pathogens, clinical pictures and risk factors of community-acquired pneumonia (CAP) in the Vietnamese adult population.

Methods

A prospective surveillance for hospitalised adult …

Intronic Non-Cg Dna Hydroxymethylation And Alternative Mrna Splicing In Honey Bees, Pablo Cingolani, Xiaoyi Cao, Radhika S. Khetani, Chieh-Chun Chen, Melissa Coon, Alya'a Sammak, Aliccia Bollig-Fischer, Susan Land, Yun Huang, Matthew E. Hudson, Mark D. Garfinkel, Sheng Zhong, Gene E. Robinson, Douglas M. Ruden

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Previous whole-genome shotgun bisulfite sequencing experiments showed that DNA cytosine methylation in the honey bee (Apis mellifera) is almost exclusively at CG dinucleotides in exons. However, the most commonly used method, bisulfite sequencing, cannot distinguish 5-methylcytosine from 5-hydroxymethylcytosine, an oxidized form of 5-methylcytosine that is catalyzed by the TET family of dioxygenases. Furthermore, some analysis software programs under-represent non-CG DNA methylation and hydryoxymethylation for a variety of reasons. Therefore, we used an unbiased analysis of bisulfite sequencing data combined with molecular and bioinformatics approaches to distinguish 5-methylcytosine from 5-hydroxymethylcytosine. By doing this, we have performed the first whole …

A Novel Community-Based Study To Address Disparities In Hypertension And Colorectal Cancer: A Study Protocol For A Randomized Control Trial, Joseph Ravenell, Hayley Thompson, Helen Cole, Jordan Plumhoff, Gia Cobb, Lola Afolabi, Carla Boutin-Foster, Martin Wells, Marian Scott, Gbenga Ogedegbe

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Black men have the greatest burden of premature death and disability from hypertension (HTN) in the United States, and the highest incidence and mortality from colorectal cancer (CRC). While several clinical trials have reported beneficial effects of lifestyle changes on blood pressure (BP) reduction, and improved CRC screening with patient navigation (PN), the effectiveness of these approaches in community-based settings remains understudied, particularly among Black men.

Methods/design

MISTER B is a two-parallel-arm randomized controlled trial that will compare the effect of a motivational interviewing tailored lifestyle intervention (MINT) versus a culturally targeted PN intervention on improvement of BP …

Reviewer Acknowledgement 2013, Thomas Liehr, Henry Heng, Yuri Yurov

Wayne State University Associated BioMed Central Scholarship

Contributing reviewers

The editors of Molecular Cytogenetics would like to thank all our reviewers who have contributed to the journal in volume 5 (2012).

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 …

Resource Availability, Mortality And Fertility: A Path Analytic Approach To Global Life History Variation, Mark A. Caudell, Robert J. Quinlan

Human Biology Open Access Pre-Prints

Humans exhibit considerable diversity in timing and rate of reproduction. Life history theory suggests that ecological cues of resource richness and survival probabilities shape human phenotypes across populations. Populations experiencing high extrinsic mortality due to uncertainty in resources should exhibit faster life histories. Here we use a path analytic approach informed by life history theory to model the multiple pathways between resources, mortality rates, and reproductive behavior in 191 countries. Resources that account for the most variance in population mortality rates are predicted to explain the most variance in total fertility rates. Results indicate that resources (e.g., calories, sanitation, education, …

Book Review: Reproduction And Adaptation: Topics In Human Reproductive Ecology, Geoff Kushnick Phd

Human Biology Open Access Pre-Prints

Reproduction and Adaptation: Topics in Human Reproductive Ecology. Edited by C.G. Mascie-Taylor and Lyliane Rosetta. Cambridge Studies in Biological and Evolutionary Anthropology, Vol. 59. Cambridge: Cambridge University Press. 2011. 282 pp. $99.00 (hardback). ISBN 978-0-521-50963-3.

Down-Weighting Overlapping Genes Improves Gene Set Analysis, Adi Tarca, Sorin Draghici, Gaurav Bhatti, Roberto Romero

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The identification of gene sets that are significantly impacted in a given condition based on microarray data is a crucial step in current life science research. Most gene set analysis methods treat genes equally, regardless how specific they are to a given gene set.

Results

In this work we propose a new gene set analysis method that computes a gene set score as the mean of absolute values of weighted moderated gene t-scores. The gene weights are designed to emphasize the genes appearing in few gene sets, versus genes that appear in many gene sets. We demonstrate the …

Genetic Variation In Glutathione S-Transferase Omega-1, Arsenic Methyltransferase And Methylene-Tetrahydrofolate Reductase, Arsenic Exposure And Bladder Cancer: A Case–Control Study, Jennifer L. Beebe-Dimmer, Priyanka T. Iyer, Jerome O. Nriagu, Greg R. Keele, Shilpin Mehta, Jaymie R. Meliker, Ethan M. Lange, Ann G. Schwartz, Kimberly A. Zuhlke, David Schottenfeld, Kathleen A. Cooney

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer.

Methods

Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a …

Recent Updates On The Role Of Micrornas In Prostate Cancer, Oudai Hassan, Aamir Ahmad, Seema Sethi, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that are involved in several important biological processes through regulation of genes post-transcriptionally. Carcinogenesis is one of the key biological processes where miRNAs play important role in the regulation of genes. The miRNAs elicit their effects by binding to the 3' untranslated region (3'UTR) of their target mRNAs, leading to the inhibition of translation or the degradation of the mRNA, depending on the degree of complementary base pairing. To-date more than 1,000 miRNAs are postulated to exist, although the field is moving rapidly. Currently, miRNAs are becoming the center of interest in a …

Erlin2 Promotes Breast Cancer Cell Survival By Modulating Endoplasmic Reticulum Stress Pathways, Guohui Wang, Gang Liu, Xiaogang Wang, Seema Sethi, Rouba Ali-Fehmi, Judith Abrams, Ze Zheng, Kezhong Zhang, Stephen Ethier, Zeng-Quan Yang

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Amplification of the 8p11-12 region has been found in approximately 15% of human breast cancer and is associated with poor prognosis. Previous genomic analysis has led us to identify the endoplasmic reticulum (ER) lipid raft-associated 2 (ERLIN2) gene as one of the candidate oncogenes within the 8p11-12 amplicon in human breast cancer, particularly in the luminal subtype. ERLIN2, an ER membrane protein, has recently been identified as a novel mediator of ER-associated degradation. Yet, the biological roles of ERLIN2 and molecular mechanisms by which ERLIN2 coordinates ER pathways in breast carcinogenesis remain unclear.

Methods

We established the MCF10A-ERLIN2 …

How To Write An Article: Preparing A Publishable Manuscript!, Vinod B. Shidham, Martha B. Pitman, Richard M. Demay

Department of Pathology

Most of the scientific work presented as abstracts (platforms and posters) at various conferences have the potential to be published as articles in peer-reviewed journals. This DIY (Do It Yourself) article on how to achieve that goal is an extension of the symposium presented at the 36th European Congress of Cytology, Istanbul, Turkey (presentation available on net at http://alturl.com/q6bfp). The criteria for manuscript authorship should be based on the ICMJE (International Committee of Medical Journal Editors) Uniform Requirements for Manuscripts. The next step is to choose the appropriate journal to submit the manuscript and review the 'Instructions to …

Copy Number Variation Signature To Predict Human Ancestry, Melissa Pronold, Marzieh Vali, Roger Pique-Regi, Shahab Asgharzadeh

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Copy number variations (CNVs) are genomic structural variants that are found in healthy populations and have been observed to be associated with disease susceptibility. Existing methods for CNV detection are often performed on a sample-by-sample basis, which is not ideal for large datasets where common CNVs must be estimated by comparing the frequency of CNVs in the individual samples. Here we describe a simple and novel approach to locate genome-wide CNVs common to a specific population, using human ancestry as the phenotype.

Results

We utilized our previously published Genome Alteration Detection Analysis (GADA) algorithm to identify common ancestry …

Genetic Studies Of Complex Human Diseases: Characterizing Snp-Disease Associations Using Bayesian Networks, Bing Han, Xue-Wen Chen, Zohreh Talebizadeh, Hua Xu

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Detecting epistatic interactions plays a significant role in improving pathogenesis, prevention, diagnosis, and treatment of complex human diseases. Applying machine learning or statistical methods to epistatic interaction detection will encounter some common problems, e.g., very limited number of samples, an extremely high search space, a large number of false positives, and ways to measure the association between disease markers and the phenotype.

Results

To address the problems of computational methods in epistatic interaction detection, we propose a score-based Bayesian network structure learning method, EpiBN, to detect epistatic interactions. We apply the proposed method to both simulated datasets and …

Sex Differences In The Dopaminergic Regulation Of Courtship, But Not Pairing Behaviors In Zebra Finches, Erin Marie Lowrey

Wayne State University Theses

Dopamine is one of the key ingredients in the glue that cements social bonds in vertebrates. The D2 dopamine receptor has been implicated in the regulation of monogamous pair bonding in the prairie vole. While dopamine affects courtship behaviors in the male zebra finch, the behavioral role of dopamine acting at D2 receptors in both males and females deserves further attention. We hypothesized that the D2 receptor would regulate courtship and pairing behaviors in the male and female zebra finch. Sixteen males and females were tested using a repeated measures design. On day 1, the zebra finches were injected with …

Understanding The Gender-Based Mechanism Of Mso In Als Mice: A Metabolic Characterization Of The Sod1-G93a Mouse Model, Monica Ann Bame

Wayne State University Dissertations

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron death and a corresponding loss of neuromuscular connections resulting in muscle atrophy. Patients become paralyzed shortly after symptom onset and typically die within one to five years of pulmonary complications. ALS is a relatively rare disease, with an overall incidence of approximately 2 in 100,000 people per year and a prevalence of about 5 in 100,000 people. It is typically associated with increasing age and has a slight male prevalence, with a male to female ratio of approximately 3:2. ALS is classified as either familial (the less …

Predicting Vision Loss In Healthy Aging With Manganese-Enhanced Mri Of The Rat Eye, David Bissig

Wayne State University Dissertations

In healthy aging, visual function declines throughout adulthood. Age-related changes in neuronal ion homeostasis -- specifically, increased Ca2+ influx through L-type voltage gated calcium channels (L-VGCCs) -- are believed to contribute to certain functional declines, but this possibility has not yet been tested in the neural retina. In young, mid- and old adult Long-Evans rats, we compared visual function (optokinetic tracking), as well as retinal physiology and eye morphology (Mn2+-enhanced MRI (MEMRI), which uses neuronal Mn2+ uptake as a marker of Ca2+ influx). We documented significant age-related decreases in visual performance and increases in retinal ion influx. We confirmed that …

Gestation Length, Mode Of Delivery And Neonatal Line Thickness Variation, CléMent Zanolli, Luca Bondioli, Franz Manni, Paola Rossi, Roberto Macchiarelli

Human Biology Open Access Pre-Prints

The transition from an intra- to extra-uterine environment leaves its mark in deciduous teeth (and first permanent molars) as an accentuated enamel incremental ring called the neonatal line (NL). This prominent microfeature separates the enamel formed during intrauterine life from that formed after leaving the womb. However, while the physical structure of this scar is well known, the bases of its formation are still a matter of investigation. In particular, besides the influence of the birth-related abrupt environmental and dietary changes and the role played by physiological factors such as hypocalcaemia, it has been suggested a direct relationship between NL …

The Pax Gene Eyegone Facilitates Repression Of Eye Development In Tribolium, Nazanin Zarinkamar, Xiaoyun Yang, Riyue Bao, Frank Friedrich, Rolf Beutel, Markus Friedrich

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The Pax transcription factor gene eyegone (eyg) participates in many developmental processes in Drosophila, including the Notch signaling activated postembryonic growth of the eye primordium, global development of the adult head and the development of the antenna. In contrast to other Pax genes, the functional conservation of eyg in species other than Drosophila has not yet been explored.

Results

We investigated the role of eyg during the postembryonic development of the red flour beetle Tribolium castaneum. Our results indicate conserved roles in antennal but not in eye development. Besides segmentation defects in the antenna, Tribolium eyg knockdown animals …