Medical Cell Biology Commons^™

Serotonergic Innervation And Serotonin Receptor Expression Of Npy-Producing Neurons In The Rat Lateral And Basolateral Amygdaloid Nuclei., M Bonn, A Schmitt, K-P Lesch, E J Van Bockstaele, E Asan

Department of Neuroscience Faculty Papers

Pharmacobehavioral studies in experimental animals, and imaging studies in humans, indicate that serotonergic transmission in the amygdala plays a key role in emotional processing, especially for anxiety-related stimuli. The lateral and basolateral amygdaloid nuclei receive a dense serotonergic innervation in all species studied to date. We investigated interrelations between serotonergic afferents and neuropeptide Y (NPY)-producing neurons, which are a subpopulation of inhibitory interneurons in the rat lateral and basolateral nuclei with particularly strong anxiolytic properties. Dual light microscopic immunolabeling showed numerous appositions of serotonergic afferents on NPY-immunoreactive somata. Using electron microscopy, direct membrane appositions and synaptic contacts between serotonin-containing axon …

Lps And Pan-Induced Podocyte Injury In An In Vitro Model Of Minimal Change Disease: Changes In Tlr Profile., Tarak Srivastava, Mukut Sharma, Kok-Hooi Yew, Ram Sharma, R Scott Duncan, Moin A. Saleem, Ellen T. Mccarthy, Alexander Kats, Patricia A. Cudmore, Uri S. Alon, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

Minimal change disease (MCD), the most common idiopathic nephrotic syndrome in children, is characterized by proteinuria and loss of glomerular visceral epithelial cell (podocyte) ultrastructure. Lipopolysaccharide (LPS) and puromycin aminonucleoside (PAN) are used to study podocyte injury in models of MCD in vivo and in vitro. We hypothesized that LPS and PAN influence components of the innate immune system in podocytes such as the Toll-Like Receptor (TLRs), TLR adapter molecules, and associated cytokines. Our results show that cultured human podocytes constitutively express TLRs 1-6 and TLR-10, but not TLRs 7-9. LPS (25 μg/ml) or PAN (60 μg/ml) caused comparable derangement …

Cytoplasmic Localization Of Alteration/Deficiency In Activation 3 (Ada3) Predicts Poor Clinical Outcome In Breast Cancer Patients., Sameer Mirza, Emad A. Rakha, Alaa Alshareeda, Shakur Mohibi, Xiangshan Zhao, Bryan J. Katafiasz, Jun Wang, Channabasavaiah B. Gurumurthy, Aditya Bele, Ian O. Ellis, Andrew R. Green, Hamid Band, Vimla Band

Journal Articles: Genetics, Cell Biology & Anatomy

Transcriptional activation by estrogen receptor (ER) is a key step to breast oncogenesis. Given previous findings that ADA3 is a critical component of HAT complexes that regulate ER function and evidence that overexpression of other ER coactivators such as SRC-3 is associated with clinical outcomes in breast cancer, the current study was designed to assess the potential significance of ADA3 expression/localization in human breast cancer patients. In this study, we analyzed ADA3 expression in breast cancer tissue specimens and assessed the correlation of ADA3 staining with cancer progression and patient outcome. Tissue microarrays prepared from large series of breast cancer …

The Role Of Dax-1 In Regulating Pluripotency In Mouse Embryonic Stem Cells, Anthony Torres

Master's Theses

The orphan receptor Dax-1 is highly expressed in pluripotent embryonic stem (ES) cells and shows a correlative reduction in expression as these cells differentiate. While it is known that Dax-1 is expressed in pluripotent mouse ES cells, the precise function of Dax-1 in these cells is not as well understood. Recent studies employing RNA interference (RNAi) to specifically reduce the expression of the Dax-1 gene in mouse ES cells found that upon the knock down of Dax-1, ES cells differentiated. These findings indicate that Dax-1 functions in a novel role in the maintenance of a relatively undifferentiated state in ES …

Role Of Iron In Ethanol Derived Hepatic Stress, Jesse A. Thornton

Theses, Dissertations and Capstones

Chronic alcohol abuse is the third leading cause of preventable death in the United States. Ethanol metabolism causes liver injury through alterations in hepatic metabolic state, redox status, and acetaldehyde adduct formations. Increased iron absorption is associated with chronic ethanol consumption and may play a role in ethanol induced oxidative stress. We tested the hypothesis that normal labile iron in the liver plays a role in ethanol related pathological stress, using C57/Bl6 mice pair-fed Lieber-DeCarli liquid ethanol diets for 11 and 22 weeks. Normal iron group mice received 55mg/kg iron as ferric citrate, whereas the low iron groups received 5mg/kg. …

Influence Of Exposure To Benzo[A]Pyrene On Mice Testicular Germ Cells During Spermatogenesis, Hueiwang Anna Jeng, Silvina M. Bocca

Community & Environmental Health Faculty Publications

The objective of this study was to assess the toxicological effect of exposure to benzo(a)pyrene, B[a]P, on germ cells during spermatogenesis. Mice were exposed to B[a]P at 1, 10, 50, and 100 mg/kg/day for 30 days via oral ingestion. Germ cells, including spermatogonia, spermatocytes, pachytene spermatocytes, and round spermatids, were recovered from testes of mice exposed to B[a]P, while mature spermatozoa were isolated from vas deferens. Reproductive organs were collected and weighed. Apoptotic response of germ cells and mature spermatozoa were qualified using the terminal deoxynucleotidyl transferase mediated deoxy-UTP nick end labeling (TUNEL) assay. B[a]P exposure at

Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco

Graduate School of Biomedical Sciences Theses and Dissertations

Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …

Multifactorial Modulation Of The Blood-Brain Barrier: Relationship To Stroke, Bei Zhang

Theses and Dissertations--Nutritional Sciences

The blood-brain barrier (BBB) is a dynamic interface, mainly consisting of highly specialized brain microvascular endothelial cells (BMECs) that segregate the central nervous system (CNS) from the peripheral circulation. Impairment of the BBB, due to disruption of tight junction (TJ) proteins and inflammatory responses, may initiate and/or contribute to the progress of CNS disorders, including stroke. Stroke is the second leading cause of death worldwide. It has been shown that aging and environmental pollutants can induce brain endothelium dysfunction, and are considered as risk factors for stroke.

Deficiency of telomerase is highly linked with aging-associated vascular diseases. Evidence indicates that …

Novel Insights Into The Function And Regulation Of Group X Secretory Phospholipase A2, Joseph D. Layne Jr

Theses and Dissertations--Nutritional Sciences

Group X secretory phospholipase A₂ (GX sPLA₂) hydrolyzes membrane phospholipids producing free fatty acids and lysophospholipids. Previous studies from our lab suggest that mice with targeted deletion of GX sPLA₂ (GX KO) have increased age-related weight gain due to an increase in overall adiposity. Paradoxically, this increased adiposity is associated with improved age-related glucose intolerance. GX KO mice also demonstrate a reduced inflammatory response to lipopolysaccharide injection. In vitro studies indicate this phenotype may be attributable to blunted macrophage mediated inflammatory responses. Given the role of macrophages in promoting adipose tissue (AT) inflammation and metabolic dysfunction …

Discovering Protein Functions And Career Goals: The Suppressor Sike, Rebekah Rifareal

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Discovering IMSD was accidental. I was having a routine advising appointment and discussing future careers when the topic surfaced. At the time, I had no clue about what I wanted to do, so my advisor suggested that I explore research and encouraged me to apply for the program.

Redox-Regulated Relb-Ar Axis Mediates Prostate Specific Antigen Expression: Insight In Prostate Cancer Response To Radiation Therapy, Lu Miao

Theses and Dissertations--Toxicology and Cancer Biology

Although the prostate specific antigen (PSA) test is widely used in clinical settings for prostate cancer (PCa) diagnosis and post-treatment follow-up monitoring, false positive PSA test results, which contribute to over-diagnosis of PCa, and false negative results, which miss some patients with aggressive PCa, remain problems of clinical importance.

Our study demonstrates that radiation therapy, which is widely used for treatment of localized PCa, generates TNF-α in tumor cells and stromal fibroblasts, redox dependently. Interestingly, TNF-α rapidly and transiently triggers the RelA-mediated NF-κB canonical pathway, but its effect on RelB expression is more robust and long lasting, which leads to …

Chlamydia Pneumoniae Infection Of Neuronal Cells Induces Changes In Calcium-Associated Gene Expression Consistent With Alzheimer’S Disease, Christopher Andrew Cappellini, Ahmad B. Cader, Keith G. Williams, Juliana Zoga, Susan T. Hingley

Scholarly Posters

Background and Significance: Previous studies have shown that cells infected with Chlamydia pneumoniae (Cpn) exhibit altered gene expression consistent with that observed in Alzheimer’s disease (AD). Furthermore, AD neurodegeneration has been linked to dysregulation of intracellular calcium and calcium-related processes. Therefore, we hypothesize that one mechanism by which pathogenesis evolves in AD is through infection-induced changes in expression of calcium-related genes. Objectives: To determine if infection of neuronal cells with Cpn alters expression of calciumrelated genes associated with neurodegeneration. Methods: SK-N-MC neuronal cells were infected with Cpn (AR39 strain; MOI=1) for 3 to 72 hours, then calcium-related genes were screened …

Microparticle Function, Leorra Kohen

The Science Journal of the Lander College of Arts and Sciences

Microparticles are emerging as an integral part of the vascular system. The microparticles are derived from stimulated or apoptotic endothelial cells, platelets, and leukocytes. They are involved in coagulation and regular cell function. Excessive numbers of microparticles contribute to artherosclerosis, chronic renal failure, and metabolic syndrome. Microparticle levels may be reduced by medications, relieving symptoms for awhile. Studies are being done to predict disease by counting microparticles. Further research must be done to understand and make use of microparticles.

Amalgamation Of Nucleosides And Amino Acids In Antibiotic Biosynthesis, Sandra H. Barnard

Theses and Dissertations--Pharmacy

The rapid increase in antibiotic resistance demands the identification of novel antibiotics with novel targets. One potential antibacterial target is the biosynthesis of peptidoglycan cell wall, which is both ubiquitous and necessary for bacterial survival. Both the caprazamycin-related compounds A-90289 and muraminomicin, as well as the capuramycin-related compounds A-503083 and A-102395 are potent inhibitors of the translocase I enzyme, one of the key enzymes required for cell wall biosynthesis. The caprazamycin-related compounds contain a core nonproteinogen b-hydroxy-a-amino acid referred to as 5’-C-glycyluridine (GlyU). Residing within the biosynthetic gene clusters of the aforementioned compounds is a shared open reading …

Purpose And Criteria For Blood Smear Scan, Blood Smear Examination, And Blood Smear Review., Gene Gulati, Jinming Song, Alina Dulau Florea, Jerald Gong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A microscopic examination of an appropriately prepared and well-stained blood smear by a knowledgeable laboratory professional is necessary and clinically useful in a number of circumstances and for a variety of reasons. In this article, an attempt is made to delineate the purpose and criteria for blood smear examination in a variety of circumstances that are encountered in everyday laboratory hematology practice. A blood smear scan serves to at least (a) verify the flagged automated hematology results and (b) determine if a manual differential leukocyte count needs to be performed. Blood smear examination/manual differential leukocyte count with complete blood count …

The Contributions Of Hif-Target Genes To Tumor Growth In Rcc., Ting Zhang, Xiaohua Niu, Lili Liao, Eun-Ah Cho, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Somatic mutations or loss of expression of tumor suppressor VHL happen in the vast majority of clear cell Renal Cell Carcinoma, and it's causal for kidney cancer development. Without VHL, constitutively active transcription factor HIF is strongly oncogenic and is essential for tumor growth. However, the contribution of individual HIF-responsive genes to tumor growth is not well understood. In this study we examined the contribution of important HIF-responsive genes such as VEGF, CCND1, ANGPTL4, EGLN3, ENO2, GLUT1 and IGFBP3 to tumor growth in a xenograft model using immune-compromised nude mice. We found that the suppression of VEGF or CCND1 impaired …

Scfslimb Ubiquitin Ligase Suppresses Condensin Ii–Mediated Nuclear Reorganization By Degrading Cap-H2, Daniel W. Buster, Scott G. Daniel, Huy Q. Nguyen, Sarah L. Windler, Lara C. Skwarek, Maureen Peterson

Dartmouth Scholarship

Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. Condensin II uniquely localizes to chromatin throughout the cell cycle and, in addition to its mitotic duties, modulates chromosome organization and gene expression during interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate condensin II during interphase are unclear. Here, we report that condensin II is inactivated when its subunit Cap-H2 is targeted for degradation by the SCF(Slimb) ubiquitin ligase complex and that disruption of this process dramatically changed interphase chromatin organization. Inhibition of SCF(Slimb) function reorganized interphase chromosomes into dense, compact domains and disrupted …

Different Mechanisms Of Inflammation Induced In Virus And Autoimmune-Mediated Models Of Multiple Sclerosis In C57bl6 Mice., Abhinoy Kishore, Anurag Kanaujia, Soma Nag, A M Rostami, Lawrence C. Kenyon, Kenneth S Shindler, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system (CNS). Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59) induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE), a mainly CD4(+) T-cell-mediated disease, although CD8(+) T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as …

Inhibition Of The Host Translation Shutoff Response By Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy, Kerstin Radtke, Luc English, Christiane Rondeau, David Leib

Dartmouth Scholarship

Macroautophagy is a cellular pathway that degrades intracellular pathogens and contributes to antigen presentation. Herpes simplex virus 1 (HSV-1) infection triggers both macroautophagy and an additional form of autophagy that uses the nuclear envelope as a source of membrane. The present study constitutes the first in-depth analysis of nuclear envelope-derived autophagy (NEDA). We established LC3a as a marker that allowed us to distinguish between NEDA and macroautophagy in both immunofluorescence and flow cytometry. NEDA was observed in many different cell types, indicating that it is a general response to HSV-1 infection. This autophagic pathway is known to depend on the …

Identification Of Potential Synthetic Lethal Genes To P53 Using A Computational Biology Approach, Xiaosheng Wang, Richard Simon

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND:

Identification of genes that are synthetic lethal to p53 is an important strategy for anticancer therapy as p53 mutations have been reported to occur in more than half of all human cancer cases. Although genome-wide RNAi screening is an effective approach to finding synthetic lethal genes, it is costly and labor-intensive.

METHODS:

To illustrate this approach, we identified potentially druggable genes synthetically lethal for p53 using three microarray datasets for gene expression profiles of the NCI-60 cancer cell lines, one next-generation sequencing (RNA-Seq) dataset from the Cancer Genome Atlas (TCGA) project, and one gene expression data from the Cancer …