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Theses/Dissertations

2013

Cell Biology

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Articles 61 - 90 of 111

Full-Text Articles in Life Sciences

Control Of The Tumor Suppressor P53 By Regulating Mdm2 Activity And Stability, Ruchira S. Ranaweera Jan 2013

Control Of The Tumor Suppressor P53 By Regulating Mdm2 Activity And Stability, Ruchira S. Ranaweera

Publicly Accessible Penn Dissertations

p53 is a tumor suppressor that is widely mutated or deleted in cancer cells. Mdm2, an E3 ubiquitin ligase, is the master regulator of p53. It targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. There are complex regulatory mechanisms balancing the activity and stability of Mdm2 in a cell. Mdm2 has an extremely short half-life in the unstressed cell and its regulation is not well understood. Like most E3 ligases, Mdm2 can autoubiquitinate. Previously, the sole function of autoubiquitination was thought to be to signal Mdm2 degradation. Here I show that ...


The Interplay Between Lewy Body-Like Alpha-Synuclein Aggregates Nd Protein Degradation Pathways In Cell-Based Model Of Parkinson's Disease, Selcuk Aski Tanik Jan 2013

The Interplay Between Lewy Body-Like Alpha-Synuclein Aggregates Nd Protein Degradation Pathways In Cell-Based Model Of Parkinson's Disease, Selcuk Aski Tanik

Publicly Accessible Penn Dissertations

Cytoplasmic alpha-synuclein (a-syn) aggregates, including Lewy bodies (LBs), are pathological hallmarks of a number of neurodegenerative diseases, most notably Parkinson's disease (PD). Activation of intracellular protein degradation pathways (Pdps) to eliminate these aggregates has been proposed as a therapeutic approach for PD and other synucleinopathies, but the interplay between LB-like a-syn aggregates and Pdps is not completely understood. Here, we investigate this interplay by utilizing a recently developed cellular model in which intracellular LB-like a-syn inclusions accumulate after delivery of pre-formed a-syn fibrils (Pffs) into a-syn-expressing HEK293 cells or cultured primary neurons. This thesis describes the interplay between LB-like ...


Investigation Of Mesenchymal Stem Cells And The Development Of Experimental Strategies For Rescuing Glaucomatous Eyes Using A Stem Cell-Based Therapy, Eun-Ah Ye Jan 2013

Investigation Of Mesenchymal Stem Cells And The Development Of Experimental Strategies For Rescuing Glaucomatous Eyes Using A Stem Cell-Based Therapy, Eun-Ah Ye

Graduate Theses and Dissertations

Glaucoma, the second leading cause of blindness in the world, is a hereditary ocular disease and about 60 million people suffer from it. However, currently there are no remedies to cure glaucoma. As a potential solution to rescue degenerating retinas, stem cells have been investigated extensively and the effects of morphological neuroprotection or functional recovery have been reported. In the present studies, I aimed to investigate two main topics of research. From the first topic, we demonstrated MSCs from Brown Norway rats are a self-renewing, multi-potent population. More importantly, we provide the first evidence that bone marrow MSCs are capable ...


Functional And Mutational Analysis Of Human Recq-Like Dna Helicases In Saccharomyces Cerevisiae, Hamed Mirzaei-Souderjani Jan 2013

Functional And Mutational Analysis Of Human Recq-Like Dna Helicases In Saccharomyces Cerevisiae, Hamed Mirzaei-Souderjani

Graduate Theses and Dissertations

RecQ-like proteins are a family of DNA helicases that are evolutionary conserved from prokaryotes to eukaryotes. A large amount of experimental evidence suggests these proteins have a major role in the maintenance of genome stability. In humans five RecQ like helicase have been identified (RecQL1, BLM, WRN, RecQL4, and RecQL5), three of which are associated with rare genetic disorders with sever chromosomal and developmental abnormalities, and an elevated predisposition to cancer. Among the disease associated RecQ-like helicases, BLM and WRN have been subject to extensive research, while our collective knowledge about the function of RecQL4 is still very limited. Similarly ...


Sirt1 Regulation Of The Heat Shock Response In An Hsf1-Dependent Manner And The Impact Of Caloric Restriction, Rachel Rene Raynes Jan 2013

Sirt1 Regulation Of The Heat Shock Response In An Hsf1-Dependent Manner And The Impact Of Caloric Restriction, Rachel Rene Raynes

Graduate Theses and Dissertations

The heat shock response (HSR) is the cell's molecular reaction to protein damaging stress and is critical in the management of denatured proteins. Activation of HSF1, the master transcriptional regulator of the HSR, results in the induction of molecular chaperones called heat shock proteins (HSPs). Transcription of hsp genes is promoted by the hyperphosphorylation of HSF1, while the attenuation of the HSR is regulated by a dual mechanism involving negative feedback inhibition from HSPs and acetylation at a critical lysine residue within the DNA binding domain of HSF1, which results in a loss of affinity for DNA. SIRT1 is ...


Drug Resistance Mechanisms To Gamma-Secretase Inhibitors In Human Colon Cancer Cells, Cindy R. Timme Jan 2013

Drug Resistance Mechanisms To Gamma-Secretase Inhibitors In Human Colon Cancer Cells, Cindy R. Timme

Graduate Theses and Dissertations

Colorectal cancer is the third leading cause of cancer-related mortality. Much progress has been achieved in combating this disease with surgical resection and chemotherapy in combination with targeted drugs. However, most metastatic patients develop drug resistance so new modalities of treatment are needed.

Notch signaling plays a vital role in intestinal homeostasis, self-renewal, and cell fate decisions during post-development and is activated in colorectal adenocarcinomas. Under debate is its role in carcinomas and metastatic disease. In theory, blocking Notch activation using gamma-secretase inhibitors (GSIs) may show efficacy alone or in combination with chemotherapy in the treatment of colon cancer.

In ...


Epigenetic Modifiers To Augment The Immunogenicity Of Chronic Lymphocytic Leukemia, Jason A. Dubovsky Jan 2013

Epigenetic Modifiers To Augment The Immunogenicity Of Chronic Lymphocytic Leukemia, Jason A. Dubovsky

Graduate Theses and Dissertations

Cancer cells employ a litany of immunosuppressive and immunevasive strategies to avoid detection and elimination by the various arms of the innate and adaptive immune system. Many hematologic and solid tumors progressively develop a specialized microenvironment which promotes tissue restructuring inflammation while masking the immune signature of the tumor cells themselves. Chronic lymphocytic leukemia, a malignancy of mature B lymphocytes must constantly balance on the precipice of immune recognition. A mature antigen presenting cell themselves, CLL clonal growth is dependent on the very interactions which, if effective, could potentially lead to their demise. To circumvent this, CLL clones set up ...


Gene Transfer In A Newly Established Spontaneous Feline Fibrosarcoma Cell Line, Rounak Nande Jan 2013

Gene Transfer In A Newly Established Spontaneous Feline Fibrosarcoma Cell Line, Rounak Nande

Theses, Dissertations and Capstones

Fibrosarcoma is a deadly disease in cats and is most often located at classical vaccine injections sites. More rare forms of spontaneous non-vaccination site (NSV) fibrosarcomas have been described and have been found associated to genetic alterations.

Purpose of this study was to compare the efficacy of adenoviral gene therapy in NVS fibrosarcoma. The NVS fibrosarcoma cell line (Cocca-6A) was isolated from a spontaneous fibrosarcoma that occurred in a domestic calico cat. Cocca-6A fibrosarcoma cells were morphologically and cytogenetically characterized. The feline cells were karyotyped and their chromosome number was counted using a Giemsa staining. Giemsa block staining of metaphase ...


The Role Of Tipe2 In The Regulation Of Inflammation And Tumorigenesis, Derek Johnson Jan 2013

The Role Of Tipe2 In The Regulation Of Inflammation And Tumorigenesis, Derek Johnson

Publicly Accessible Penn Dissertations

TIPE2 is a recently discovered regulator of immunity and inflammation. Here we describe a new function of TIPE2 in the regulation of Ras signaling and Tumorigenesis. By using various stimuli and inhibitors in T Cells and macrophages we discovered that TIPE2 is regulated at both the message and protein level by inflammatory stimuli. TIPE2 mRNA is regulated in the short to intermediate term by an NF-Kappa B induced micro RNA, and TIPE2 is also ubiquitylated and degraded, possibly by SCF-Beta TRCP. Mechanistically TIPE2 interacts with and inhibits the Ras-interacting domain of the RalGDS family of Ras effectors, leading to a ...


Epigenetic Basis For The Oncogenic Potential Of Idh Mutations, Chao Lu Jan 2013

Epigenetic Basis For The Oncogenic Potential Of Idh Mutations, Chao Lu

Publicly Accessible Penn Dissertations

Although many complex diseases including cancer manifest aberrant cellular metabolism and chromatin structure, the molecular connection between two processes remains poorly understood. The metabolite, α-ketoglurate (αKG), is a critical co-factor for a number of chromatin modifying enzymes. Its structural analogue, 2-hydroxyglutarate (2HG), was recently identified as the product of cancer-associated mutations in isocitrate dehydrogenases (IDH). To determine whether metabolic perturbation can disrupt chromatin remodeling and transcription, I investigated the epigenetic consequences of 2HG-producing IDH mutations. In this thesis, 2HG was demonstrated to be a competitive inhibitor for αKG-dependent chromatin modifiers including TET family DNA hydroxylases and jumonji-C histone demethylases. Expression ...


Host-Apicomplexan Parasite Interactions: Leveraging Biological Discovery Into Antiparasitic Drug Development, Melanie Grace Millholland Jan 2013

Host-Apicomplexan Parasite Interactions: Leveraging Biological Discovery Into Antiparasitic Drug Development, Melanie Grace Millholland

Publicly Accessible Penn Dissertations

The obligate intracellular pathogens Plasmodium falciparum and Toxoplasma gondii remodel their host cell to facilitate their intracellular development and progress through their asexual life cycle, a virulent lytic cycle responsible for parasite-mediated pathogenesis. While several studies have highlighted parasite proteins that interact with the host cell during this cycle, host proteins exploited by the parasite for successful growth and conversely, host molecules evolutionarily tuned to control parasite infection remain unclear. We addressed this question from both sides of the host-parasite interaction in the hope to leverage biological discovery of host molecules involved in infection into the validation of novel drug ...


Discovering Novel Intrinsic Antiviral Responses To Arboviruses: From Transcription To Intestinal Innate Immunity, Jie Xu Jan 2013

Discovering Novel Intrinsic Antiviral Responses To Arboviruses: From Transcription To Intestinal Innate Immunity, Jie Xu

Publicly Accessible Penn Dissertations

Many (re) emerging pathogens are arthropod-borne, transmitted via an insect vector, and cause significant health and agricultural problems worldwide. Despite their significance, there are few vaccines and no targeted therapies that exist. This is at least in part due to our limited understanding of virus-host interactions and the mechanisms used by hosts to restrict infection. In particular, insect vectors play a critical role in the transmission and spread of these pathogens, but performing molecular and genetic studies has proven to be difficult. Drosophila is a model organism that shares a high degree of conservation with insect vectors and has a ...


Molecular Mechanisms Of Alternative Splicing Regulation: An Investigation Of The Spliceosome Repressed By Hnrnp L On Cd45 Exon 4, Ni-Ting Chiou Jan 2013

Molecular Mechanisms Of Alternative Splicing Regulation: An Investigation Of The Spliceosome Repressed By Hnrnp L On Cd45 Exon 4, Ni-Ting Chiou

Publicly Accessible Penn Dissertations

Alternative splicing is a key step in gene regulation and involves the differential selection of splice sites to generate different pre-mRNA transcripts. It has been shown that 90-95% of pre-mRNAs are alternatively spliced in human cells. Pre-mRNA splicing is catalyzed the spliceosome, which consists mainly of the U1, U2, U4, U5 and U6 snRNP, and about a hundred of non-snRNP proteins. Splicing regulators that bind to enhancer or silencer elements on the pre-mRNA can alter assembly of these spliceosome components. Understanding how splicing regulators control spliceosome assembly will bring insights to the prediction of splice site choices. In our lab ...


Bridging The Gap: Defining The Molecular Mechanisms Of Cep290 Disease Pathogenesis, Theodore George Drivas Jan 2013

Bridging The Gap: Defining The Molecular Mechanisms Of Cep290 Disease Pathogenesis, Theodore George Drivas

Publicly Accessible Penn Dissertations

Mutations in the gene CEP290 cause an array of debilitating and phenotypically distinct human diseases, ranging in severity from the devastating blinding disease Leber congenital amaurosis (LCA) to Senior Løken Syndrome, Joubert syndrome, and the embryonically lethal Meckel-Grüber syndrome. The pathology observed in these diseases is thought to be due to CEP290's essential role in the development and maintenance of the primary cilium, but despite its critical role in biology and disease we know only little about CEP290's function. Here we identify four novel functional domains of the protein, showing that CEP290 directly binds to cellular membranes ...


Determining The Role Of Autophagy In Her2/Neu-Induced Mammary Tumor Dormancy And Recurrence, Samantha L. Dwyer Jan 2013

Determining The Role Of Autophagy In Her2/Neu-Induced Mammary Tumor Dormancy And Recurrence, Samantha L. Dwyer

Publicly Accessible Penn Dissertations

Mortality from breast cancer is principally due to tumor recurrence. Recurrent breast cancers arise from the pool of residual tumor cells, termed minimal residual disease, that survive treatment and may exist in a dormant state for up to 20 years following treatment of the primary tumor. As recurrent breast cancer is typically a fatal disease, understanding the mechanisms underlying dormant tumor cell survival is a critical priority in breast cancer research. Using a HER2/neu inducible bitransgenic mouse model, we demonstrate that the survival and recurrence of dormant mammary tumor cells is dependent on autophagy. We find that autophagy is ...


Regulation Of T Cell Receptor Signaling By Diacylglycerol Kinases And Phosphatidylinositol Transfer Proteins, Rohan Prakash Joshi Jan 2013

Regulation Of T Cell Receptor Signaling By Diacylglycerol Kinases And Phosphatidylinositol Transfer Proteins, Rohan Prakash Joshi

Publicly Accessible Penn Dissertations

Signals transduced through the T cell receptor (TCR) lead to T cell differentiation, proliferation, and elaboration of cytokines, all of which are required for optimal immunity. Phosphoinositide (PI) mediated signaling plays a particularly prominent role in this process. TCR signaling is amplified by the activation of phospholipase C γ1 (PLCγ1), which cleaves phosphatidylinositol-4,5-bisphosphate (PIP2) to form the second messengers diacylglycerol (DAG) and inositol triphosphate (IP3). Regulation of PI and products such as DAG are therefore essential for normal TCR signaling. DAG levels are reduced by diacylglycerol kinases (DGKs), which metabolize DAG and diminish DAG-mediated signaling. In T ...


Cd8+ T-Cell Responses In A Th2-Polarized Inflammatory Setting, Vanessa Christina Kurzweil Jan 2013

Cd8+ T-Cell Responses In A Th2-Polarized Inflammatory Setting, Vanessa Christina Kurzweil

Publicly Accessible Penn Dissertations

A variety of external factors can affect the activation status, effector function, and memory differentiation of T cells. Such factors include resident microbiota and the cytokine milieu produced in a host. Loss of tolerance to commensal bacteria and excess inflammatory cytokines such as IL-4 have been implicated in the pathogenesis of many diseases, including inflammatory bowel disease (IBD) and allergy. Although these diseases are traditionally associated with CD4+ T cells, it is increasingly appreciated that CD8+ T cells in these settings may either contribute to or reduce pathology. This work explores the influence of various factors on CD8+ T-cell responses ...


Genome-Wide Analysis Of Rna Secondary Structure In Eukaryotes, Fan Li Jan 2013

Genome-Wide Analysis Of Rna Secondary Structure In Eukaryotes, Fan Li

Publicly Accessible Penn Dissertations

The secondary structure of an RNA molecule plays an integral role in its maturation, regulation, and function. Over the past decades, myriad studies have revealed specific examples of structural elements that direct the expression and function of both protein-coding messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs). In this work, we develop and apply a novel high-throughput, sequencing-based, structure mapping approach to study RNA secondary structure in three eukaryotic organisms.

First, we assess global patterns of secondary structure across protein-coding transcripts and identify a conserved mark of strongly reduced base pairing at transcription start and stop sites, which we hypothesize helps ...


Regulators Of Mouse And Human Beta Cell Proliferation, Yang Jiao Jan 2013

Regulators Of Mouse And Human Beta Cell Proliferation, Yang Jiao

Publicly Accessible Penn Dissertations

Diabetes mellitus is an increasingly prevalent metabolic disorder that is estimated to affect over 300 million people by 2025. Common to either type 1 or type 2 diabetes is a progressive inadequacy of functional beta-cell mass. Recent studies have shown that during times of prolonged metabolic demand for insulin, the endocrine pancreas can respond by increasing beta-cell mass by beta-cell proliferation. Advances that further our knowledge of the molecular factors that control beta-cell proliferation will be crucial for understanding the homeostasis of beta-cell mass during adulthood, and are pivotal for any attempt to use instructive cues to induce the proliferation ...


The Role Of Arx In Specification And Maintenance Of Pancreatic Islet Α-Cells, Crystal Ley Wilcox Jan 2013

The Role Of Arx In Specification And Maintenance Of Pancreatic Islet Α-Cells, Crystal Ley Wilcox

Publicly Accessible Penn Dissertations

Correct specification and maintenance of pancreatic islet cells is an intricate process. Previous studies have demonstrated the essential role transcription factors play in this process. For islet glucagon-producing alpha-cells one such transcription factor is the aristaless-related homeobox gene (Arx). Previous studies have demonstrated that Arx is necessary and sufficient for alpha-cell specification where ablation of Arx results in complete loss of the alpha-cell lineage and misexpression leads to conversion into an alpha-cell phenotype. However, the role of Arx in maintenance of alpha-cell fate as well the impact non-null mutations of Arx have on alpha-cell development has not been explored. In ...


Cellular Mechanisms Of Mammalian Liver Regeneration, Kilangsungla Yanger Jan 2013

Cellular Mechanisms Of Mammalian Liver Regeneration, Kilangsungla Yanger

Publicly Accessible Penn Dissertations

ABSTRACT

CELLULAR MECHANISMS OF MAMMALIAN LIVER REGENERATION

Kilangsungla Yanger

Ben Z. Stanger

The liver is an essential organ that aids in metabolic processes, protein synthesis and detoxification of harmful substances. As the centre for detoxification, the liver is able to compensate for this routine damage with its robust regenerative ability. All vertebrate livers, for example, can make up for tissue mass loss (via surgical excision of a portion of the liver) by replication of their differentiated cells within the remnant lobes. These differentiated cells include parenchymal cells such as the hepatocytes and biliary epithelial cells (BECs) and also non-parenchymal cells ...


Local Cytoskeletal And Organelle Interactions Impact Molecular Motor-Driven Early Endosomal Trafficking, Allison Lorraine Zajac Jan 2013

Local Cytoskeletal And Organelle Interactions Impact Molecular Motor-Driven Early Endosomal Trafficking, Allison Lorraine Zajac

Publicly Accessible Penn Dissertations

Molecular motors generate the force needed for long-distance transport of cargos and organelles in the cell. How motor proteins attach to a diverse array of cargos and navigate to the correct location in the cell with enough fidelity to maintain organelle integrity is only starting to be understood. Studying the properties of individual motors, and their fine-tuning by regulatory molecules, is one area of active investigation in vitro. However, the organization of the cell, and the variability of the environment within a single cell, cannot be fully reconstituted in vitro. We investigated the effects of the crowded intracellular environment on ...


Camp Promotes Retinal Midline Crossing At The Zebrafish Optic Chiasm, Alison Dell Jan 2013

Camp Promotes Retinal Midline Crossing At The Zebrafish Optic Chiasm, Alison Dell

Publicly Accessible Penn Dissertations

During development, axons navigate a complex intracellular milieu, often over long distances to reach target tissues at stereotyped locations. The basis for this navigation lies in the growth cone - a motile structure at the tip of the growing axon. Studded with receptors for an array of guidance cues, the growth cone interprets a balance of attractive and repellant signals en route to its target. However, during pathfinding, axons often must extend along or near areas expressing repellents. We previously showed that growth cones can modulate their response to multiple repellents through a G protein coupled receptor, calmodulin, cAMP and PKA ...


The Multifunctional Protein Daxx: Studies Of Its Biology And Regulation, And Discovery Of A Novel Function, Trisha Agrawal Jan 2013

The Multifunctional Protein Daxx: Studies Of Its Biology And Regulation, And Discovery Of A Novel Function, Trisha Agrawal

Publicly Accessible Penn Dissertations

Daxx, a multifunctional protein with a diverse set of proposed functions, is ubiquitously expressed and highly conserved through evolution. A primarily nuclear protein, Daxx is able to regulate apoptosis, transcription, and cellular proliferation. Despite many studies into the function of Daxx, its precise role in the cell remains enigmatic. Herein, evidence is presented to expand upon the known anti-apoptotic function of Daxx, to establish Daxx as a novel molecular chaperone, and to further its repertoire of transcriptional targets. As an apoptotic inhibitor, Daxx is known to regulate p53 by stabilizing its main negative regulator, Mdm2, via formation of a ternary ...


A Nuclear-Derived Proteinaceous Matrix Embeds The Microtubule Spindle Apparatus During Mitosis, Changfu Yao Jan 2013

A Nuclear-Derived Proteinaceous Matrix Embeds The Microtubule Spindle Apparatus During Mitosis, Changfu Yao

Graduate Theses and Dissertations

ABSTRACT<

The nucleus undergoes a dramatic reorganization as the cell prepares to segregate its duplicated chromosomes during cell division. For many years s, the prevailing view was that in open mitosis the nucleus completely disassembled during early mitotic stages, thus enabling cytoplasmic microtubules emanating from the separated centrosomes to form a mitotic spindle. This cytocentric view largely discounted any nuclear contributions to regulation of mitotic progression (Johansen and Johansen, 2009; De Souza and Osmani, 2009; Simon and Wilson, 2011; Sandquist et al., 2011). A spindle matrix has long been proposed to serve as a relatively stable or elastic molecular matrix ...


Acidic Pericellular Ph: Effects On Proteolysis And Gene Expression As Determined In 3d Models Of Breast Carcinoma, Jennifer M. Rothberg Jan 2013

Acidic Pericellular Ph: Effects On Proteolysis And Gene Expression As Determined In 3d Models Of Breast Carcinoma, Jennifer M. Rothberg

Wayne State University Dissertations

Among the non-cellular microenvironmental factors that contribute to malignancy of solid tumors is an acidic peritumoral pH. The first objective was to determine if an acidic extracellular pH observed in vivo (i.e., pHe 6.8) affects the activity of proteases, such as cathepsin B, that contribute to degradation of collagen IV by tumor cells when grown in biologically relevant three-dimensional cultures. At pHe 6.8 there were increases in pericellular active cysteine cathepsins and in degradation of DQ-collagen IV, which was partially blocked by a cathepsin B inhibitor. Imaging probes for active cysteine cathepsins localized to tumors in vivo ...


The Transcriptional Regulation Of Flagellin-Induced Innate Protection Of The Cornea: Role Of Irf1 And Atf3, Gi Sang Yoon Jan 2013

The Transcriptional Regulation Of Flagellin-Induced Innate Protection Of The Cornea: Role Of Irf1 And Atf3, Gi Sang Yoon

Wayne State University Dissertations

Pre-exposure of the cornea to TLR5 ligand flagellin induces profound mucosal innate protection against infections by reprogramming gene expression. This study explored the flagellin-induced modifications of transcription factor expression and function, specifically of IRF1 and ATF3 in corneal epithelial cells to elucidate the transcriptional mechanisms underlying the protective function of flagellin on the cornea.

Initially we used Superarray to screen for transcription factors and identified Interferon Regulatory Factor (IRF) 1 and Activating Transcription Factor (ATF) 3 as the most drastically affected genes by flagellin pretreatment in P. aeruginosa challenged human corneal epithelial cells (CEC). However, flagellin pretreatment had opposite effects ...


Desensitization Of Basal Cell Carcinoma To The Anti-Tumoral Effect Of Vitamin D, Rawia Khasawneh Jan 2013

Desensitization Of Basal Cell Carcinoma To The Anti-Tumoral Effect Of Vitamin D, Rawia Khasawneh

Wayne State University Dissertations

The relationship between Vitamin D and NMSC is not very clear. Most of human studies in literature in regards to vitamin D and NMSC are epidemiological which are inconsistent and inconclusive. Mechanistic studies about BCC are few, and mostly are animal models or cell cultures. The main goal for this study is to interpret the impact of vitamin D status on the onset and progression and possibly treatment of basal cell carcinoma. Three tissue samples were collected from BCC patients (Cancer, Proximal, and Distal), and from cancer-free individuals from southeast Michigan. This study design helps identifying alterations in the genetic ...


Regulation Of The Glycine Transporter 1 (Glyt1) By Pkca-Dependent Ubiquitination, Susana Barrera Jan 2013

Regulation Of The Glycine Transporter 1 (Glyt1) By Pkca-Dependent Ubiquitination, Susana Barrera

Open Access Theses & Dissertations

Glycine is one of the major inhibitory neurotransmitters in the central nervous system. It is implicated in the regulation of motor-sensory function such as; pain perception, reflex responses, and is essential for early development of the CNS. In addition to its inhibitory actions, it acts as an obligatory co-agonist for the activation of glutamatergic NMDARs, which are of pivotal importance in the process of learning and memory, its dysfunction leads to several neurodegenerative diseases. Two high affinity Na+/Cl- dependent transporters GlyT1 and GlyT2 tightly regulate the availability of glycine present at the synapse for the activation of NMDARs and ...


Novel Copper (Ii) Mediated Transfection Nano-Systems And Biological Properties Of Pyridinium Surfactants, Sarit Pal Jan 2013

Novel Copper (Ii) Mediated Transfection Nano-Systems And Biological Properties Of Pyridinium Surfactants, Sarit Pal

Open Access Theses & Dissertations

Efficacy of gene therapy is relied upon the improvement of gene delivery vectors into mammalian cells. Although viral-based polynucleotide carriers are still considered as the most common method for gene delivery but the cost effectiveness, nonspecific lethal immune response has evoked the renaissance of non-viral synthetic delivery systems. An initial discovery by Felgnar et al showed Cationic Liposomes (CLs) (having an overall positive charge) when mixed with DNA to form CL-DNA complexes can enhance the transfer of polynucleotides into cells followed by its expression. Presently, a flurry of experimental works is taking place for the better understanding of structural characterization ...