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Mechanisms Of Resistance To Oncolytic Herpes Simplex Viruses In Malignant Peripheral Nerve Sheath Tumors, Joshua Douglas Jackson Jan 2015

Mechanisms Of Resistance To Oncolytic Herpes Simplex Viruses In Malignant Peripheral Nerve Sheath Tumors, Joshua Douglas Jackson

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Malignant peripheral nerve sheath tumors (MPNSTs) are rare but highly aggressive cancer of the peripheral nervous tissue. Median patient survival is approximately two years following diagnosis due in part to the ineffective options for treatment. As an alternative therapeutic approach to conventional radio- and chemotherapy, oncolytic herpes simplex viruses type-1 (oHSVs) have been proposed to treat MPNSTs. These oHSVs have been shown safe in clinical trials with associated tumor regression. However, there is evidence that resistance to the therapy should be anticipated in a subset of patients. Therefore, the goal of this dissertation has been to identify the primary obstacles …

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Prevalence And Determinants Of High Risk Human Papillomavirus (Hpv) Among Wives Of Migrant Workers - A Study In Far - West Nepal, Derek Johnson Jan 2015

Prevalence And Determinants Of High Risk Human Papillomavirus (Hpv) Among Wives Of Migrant Workers - A Study In Far - West Nepal, Derek Johnson

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This dissertation research focuses on the risk factors associated with high-risk HPV infection (HR-HPV) and abnormal cervical cytology in Nepali women residing in Nepal’s Far-West district of Achham. The first part of this dissertation assesses the HR-HPV test concordance of self-collected vs. clinician-collected cervico-vaginal specimens. Of 261 women with both clinician- and self-collected cervical samples, 25 tested positive for HR-HPV, resulting in an overall HR-HPV prevalence of 9.6% (95% Confidence Interval [CI]: 6.3 – 13.8). The overall Kappa value for clinician- and self-collected tests was 0.64 (95% CI: 0.48 – 0.84), indicating a “good” level of agreement. The second part …

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Joining And Assembly With Long Fiber Thermoplastic Composites, Danila Kaliberov Jan 2015

Joining And Assembly With Long Fiber Thermoplastic Composites, Danila Kaliberov

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Thermoplastic composites are used extensively in automotive, mass transit, aerospace and other commercial industries. Current industry usage is typically limited to short fiber composites formed by injection molding processes, and continuous fiber reinforced composites through processes such as autoclave molding, filament winding etc. Long fiber thermoplastics (LFT) are a class of composites known for their specific strength, corrosion resistance, impact and damping properties, as well as high production rates, recyclability, and ability for complex part fabrication. The overall objective of this research was to investigate viability of joining and assembly with long fiber thermoplastic composites. This research deals with (1) …

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Automated Processing Of Continuous Glucose Monitor (Cgm) Data To Study Onset Of Diabetes, Aman Khatri Jan 2015

Automated Processing Of Continuous Glucose Monitor (Cgm) Data To Study Onset Of Diabetes, Aman Khatri

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Diabetes is a long term condition that causes high levels of blood glucose, and it is necessary to get a complete picture of glucose levels which can lead to better treatment decision and better glucose control. The advent of Continuous Glucose Monitoring (CGM) is helping researches to track the blood glucose levels continuously and to understand the effects of impaired glucose levels on human body which in turn can lead to better treatment of diabetes. Current CGM systems process enormous amounts of data and have limitations in regards to data accuracy, precision, and reliability of raw glucose data. The inaccuracy …

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Regulation Of Cks1 Protein Turnover In Cancer Cells, Vinayak Khattar Jan 2015

Regulation Of Cks1 Protein Turnover In Cancer Cells, Vinayak Khattar

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Cks1 is a crucial cell cycle regulator which plays pleiotropic roles in cancer cell growth and is highly expressed at both the protein, and mRNA levels, in cancer cells. In contrast, normal cells exhibit barely detectable levels of this protein, even though they express substantial Cks1 mRNA. One reason for high Cks1 protein in cancers appears to be its stabilization in these cells. Cks1 is known to be ubiquitinated and degraded by the proteasome. Coordinated ubiquitination dependent proteasomal degradation of cell cycle proteins is a major mechanism that regulates their activity. Therefore aberrant accumulation of Cks1, frequently observed in cancer, …

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Evaluation Of Sample Size Re-Estimation Procedures For Non-Inferiority Designs With Time-To-Event Outcomes, Hwasoon Kim Jan 2015

Evaluation Of Sample Size Re-Estimation Procedures For Non-Inferiority Designs With Time-To-Event Outcomes, Hwasoon Kim

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Study designs that allow sample size review may potentially save a study by identifying misspecified assumptions, modifying the planned sample size, and reinforcing the study’s power. Most sample size re-estimation (SSR) methods in non-inferiority trials have been developed for continuous or binary outcomes. In many medical domains studying cancer, heart failure, and other chronic diseases, most phase III trials use censored endpoints (e.g. survival or event-free survival). Non-inferiority designs have inherent complexity by the introduction of the non-inferiority margin and therefore understanding of strategies in these methods is essential. In our first paper, we detail the issues related to misspecification …

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Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough Jan 2015

Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough

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Cerebral blood flow is regulated by vasoactive molecules released by astroglial cell processes that ensheath the entire cerebrovasculature. This regulation of blood flow in response to neuronal activity is a process known as functional hyperemia. Astrocytes, along with their associated neurons and microvessels, are organized into a functional system called the gliovascular unit (GVU). The astroglial component of the GVU is integral in both regulation of blood flow and maintenance of the blood-brain barrier (BBB). In disease, this system can be disrupted. We found that glioma cells displace astrocytic processes, called endfeet, and prevent their communication with associated vessels, leading …

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An Nphp-4 Enhancer Mutagenesis Screen For Modifiers Of Cilia Phenotypes Reveals Novel Mks Alleles, Uncovers, A Specific Genetic Interaction Between Osm-3 And Nphp-4, And A Novel Ciliary Calcium Channel., Dawn Landis Jan 2015

An Nphp-4 Enhancer Mutagenesis Screen For Modifiers Of Cilia Phenotypes Reveals Novel Mks Alleles, Uncovers, A Specific Genetic Interaction Between Osm-3 And Nphp-4, And A Novel Ciliary Calcium Channel., Dawn Landis

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Nephronophthisis (NPHP) is a ciliopathy with diverse clinical features likely caused by genetic modifiers. To identify NPHP modifiers, a screen was conducted on nphp-4(tm925) mutant C. elegans to reveal mutations that exacerbate the NPHP ciliary defects. Ten loci were generated, five of which have now been identified. Three are mutations in ciliopathy genes mks-1, mks-2, and mks-5. The fourth allele (yhw66) is a missense mutation (S316F) in OSM-3, a kinesin required for cilia distal segment assembly. As in osm-3 null mutants, nphp-4(tm925);osm-3(yhw66) mutants lack distal segments, are dye-filing defective (Dyf), and have osmotic avoidance defects (OSM). The osm-3(yhw66) mutant alone …

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14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley Jan 2015

14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley

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Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of inherited Parkinson’s disease (PD), and LRRK2 is a risk factor for idiopathic PD. How LRRK2 function is regulated is not well understood. Recently, the highly-conserved 14-3-3 proteins, which play a key role in many cellular functions including cell death, have been shown to interact with LRRK2. In this study, we investigated whether 14-3-3s can regulate mutant LRRK2-induced neurite shortening and kinase activity. In the presence of 14-3-3θ overexpression, neurite length of primary neurons from BAC transgenic G2019S-LRRK2 mice returned back to wildtype levels. Similarly, 14-3-3θ overexpression …

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Linking Adiponectin And Autophagy In The Regulation Of Breast Cancer Metastatic Potential, Emily Libby Jan 2015

Linking Adiponectin And Autophagy In The Regulation Of Breast Cancer Metastatic Potential, Emily Libby

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Curative approaches for metastatic breast cancer remain elusive. Adiponectin is the most abundant of the adipocyte-secreted adipokines, and there is recent interest in development of adiponectin-based therapies for this disease. Yet, while multiple epidemiological studies have indicated that low levels of circulating plasma adiponectin portend poorer prognosis, recent work has reported that elevated adiponectin expression in breast tissue correlates with advanced disease. Further, isoform-specific roles of this molecule are not well understood. Thus, the overarching purpose of this work was to elucidate how adiponectin isoforms contribute to the microenvironmental regulation of the early steps of breast cancer metastasis. We show …

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The Jak/Stat Pathway In Neuroinflammatory Diseases, Yudong Liu Jan 2015

The Jak/Stat Pathway In Neuroinflammatory Diseases, Yudong Liu

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Dysregulation of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is critically involved in the pathogenesis of multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE). Suppressor Of Cytokine Signaling (SOCS) proteins are the negative regulators of the JAK/STAT pathway. To determine the role of SOCS3 in myeloid cells in EAE, mice with conditional SOCS3 deletion in myeloid cells (LysMCre-SOCS3fl/fl) were created and tested. LysMCre-SOCS3fl/fl mice develop a severe, non-resolving atypical form of disease, characterized by lesions and extensive neutrophil and other inflammatory cell infiltrates in the cerebellum and brainstem, elevated STAT activation, elevated cytokine, chemokine and iNOS expression, and prominent …

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Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu Jan 2015

Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu

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Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson disease (PD) , with pathogenic mutations located within each of the two catalytic cores of the protein, the GTPase and kinase domains. The most prevalent pathogenic mutation, G2019S increases kinase activity up to 5-fold, causing significant changes in the protein’s biochemical behavior. Other mutations such as R1441G and I2020T have also been demonstrated to increase LRRK2 kinase activity, however, the detailed mechanisms remains unclear. A major limitation in the field is the lack of structural information of LRRK2. This dissertation detailed …

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Assessment Of Antipsychotic Medication Effects On Dynamic Functional Network Connectivity In Patients With Schizophrenia, Kristin Lottman Jan 2015

Assessment Of Antipsychotic Medication Effects On Dynamic Functional Network Connectivity In Patients With Schizophrenia, Kristin Lottman

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Schizophrenia, a psychiatric disorder affecting approximately 1% of the population, is often characterized as a disorder of dysconnectivity. Evaluation of the dysconnectivity hypothesis of schizophrenia has been extensively examined via functional neuroimaging studies in order to enhance insight into the disorder’s pathology. In particular, resting-state functional connectivity analyses have reported widespread aberrant network connectivity between brain regions in patients; however, consistencies in the directionality of abnormalities are often variable across studies. Recent investigations have begun to analyze functional connectivity dynamically as it is likely these inconsistencies may be a result of the static nature of traditional connectivity measures. In this …

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Some Contributions To Bayesian Regularization Methods With Applications To Genetics And Clinical Trials, Himel Mallick Jan 2015

Some Contributions To Bayesian Regularization Methods With Applications To Genetics And Clinical Trials, Himel Mallick

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Variable selection refers to the class of problems where one tries to find an optimal subset of relevant variables, which can be used to accurately predict the outcome of a certain response variable. Typically, a large number of variables are often collected; however, all but a few important variables are relevant for the prediction of the outcome, so the underlying representation is sparse. To this end, variable selection is fundamental in high-dimensional data analysis, playing a crucial role in important scientific discovery and decision-making, and has received enormous attention in the literature. Regularization method is one attractive approach that has …

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A New Form Of Rod Photoreceptor Light Adaptation, Alex S. Mckeown Jan 2015

A New Form Of Rod Photoreceptor Light Adaptation, Alex S. Mckeown

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In the first step in light perception, rod and cone photoreceptors convert photon absorption into an electrical impulse that is transmitted through the visual pathway. While the biochemistry and the signaling physiology have largely been defined in dark-adapted, isolated mammalian rods, there are still unanswered questions regarding photoreceptor light adaptation processes that involve extracellular components. In particular, the proteins of the interphotoreceptor matrix have not been considered in the studies of rod signaling and adaptation. This thesis details a new form of light adaptation, now known as adaptive potentiation (AP), in which extracellular components act on rods to transiently increase …

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Dna Methylation Regulates Neuronal Synaptic Scaling And Intrinsic Membrane Excitability, Jarrod P. Meadows Jan 2015

Dna Methylation Regulates Neuronal Synaptic Scaling And Intrinsic Membrane Excitability, Jarrod P. Meadows

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Learning and memory rely on long-lasting, experience-dependent adaptations in synaptic and non-synaptic forms of neuronal plasticity. Previous evidence implicates transcriptional and epigenetic mechanisms, including DNA cytosine methylation, as critical regulators of site-specific, Hebbian alterations in synaptic efficacy such as long-term potentiation (LTP) and long-term depression (LTD). However, whether DNA methylation modulates cell-wide, non-Hebbian homeostatic adaptations like synaptic scaling and intrinsic plasticity (IP) is unclear. Whereas synaptic scaling involves bidirectional changes in postsynaptic receptor density in response to chronic alterations in neuronal activity, IP involves the activity-dependent attunement of passive and/or active membrane properties that govern action potential (AP) firing. This …

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Nadph Oxidase-Derived Superoxide: A Potentiator Of Autoimmune Responses In Type 1 Diabetes, Lindsey E. Padgett Jan 2015

Nadph Oxidase-Derived Superoxide: A Potentiator Of Autoimmune Responses In Type 1 Diabetes, Lindsey E. Padgett

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Type 1 Diabetes (T1D) is an autoimmune disease culminating in pancreatic β-cell destruction, inducing reactive oxygen species (ROS), pro-inflammatory cytokines, and islet-infiltrating leukocutes. Macrophages, one of the first islet-infiltrating cells in T1D, secrete ROS and pro-inflammatory cytokines, which lyse pancreatic β-cells and activate diabetogenic T cells to further propagate β-cell destruction, while autoreactive CD4 T cells recruit islet-infiltrating, pro-inflammatory, M1 macrophages, and enhance CD8 T cell cytotoxicity. We previously demonstrated the importance of NADPH oxidase (NOX)-derived ROS synthesis in T1D, as Non-obese diabetic (NOD) mice lacking NOX-derived superoxide (NOD.Ncf1m1J) exhibited a delay in spontaneous and adoptive transfer of T1D. In …

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The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues Jan 2015

The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues

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Acute kidney injury (AKI), which manifests as an abrupt decline in renal function, occurs in ~1% of all hospitalization. Ischemia reperfusion injury (IRI), a common cause of AKI, can occur in any situation where blood flow to the kidney is significantly reduced such as hypertensive crisis, cardiovascular surgery, and inevitably during renal transplantation. Mortality from AKI is up to 80% due to incomplete knowledge of the pathogenesis of IRI and the lack of an effective therapy. It is thought that cellular damage as a result of hypoxia signals the release of proinflammatory cytokines that lead to a systemic inflammatory response. …

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A Prospective Randomized Clinical Trial To Assess The Performance Of Microtextured Dental Implants With Or Without A Machined Collar- 1 Year Results, Elizabeth Felts Randall Jan 2015

A Prospective Randomized Clinical Trial To Assess The Performance Of Microtextured Dental Implants With Or Without A Machined Collar- 1 Year Results, Elizabeth Felts Randall

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Aim: To assess the performance of microtextured dental implants with or without a machined collar at one year after placement. Material and Methods: Fifty-eight patients received dental implant therapy to restore missing teeth in one area of the maxilla or man-dible at the UAB Department of Graduate Periodontology. Residents in the program placed microtextured implants with a microtextured collar with microgrooves (test group) and microtextured implants with a machined collar (control group). Sites were randomized to the test group or control group. Study visit protocol was followed and implants were restored by off-site dentists. Sixty-nine (69) implants were assessed at …

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Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi Jan 2015

Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi

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The principal function of platelets is to regulate hemostasis, and dysfunction of platelet aggregation or activation can lead to either excessive thrombotic or hemorrhagic complications. It has been shown that the ability to generate ATP and exposure to oxidative stress can affect platelet thrombotic potential. While platelet metabolism has been extensively studied, the importance of substrate availability and metabolic plasticity in regulating aggregation under physiological or pathological conditions is not well understood. In this dissertation, we examined the reliance of platelets on different metabolic substrates, the importance of ATP production for aggregation in response to thrombin stimulation, metabolic stress following …

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Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert Jan 2015

Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert

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Malignant gliomas are the most prevalent primary brain tumor. They are highly aggressive and lack effective treatment options. Standard therapy includes a combination of radiation, chemotherapy, and tumor resection; however, even with aggressive treatment, median patient survival remains a dismal 12 – 14 months after diagnosis. Research has focused on understanding the unique biological mechanisms involved in glioma growth and survival in an effort to design novel therapies to treat this devastating disease. In the unique environment of the brain, gliomas have developed the ability to grow and survive at the cost of the normal surrounding brain tissue. Glutamate, the …

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Stress, Bullying, Cortisol, And Depresive Symptoms In 9th Grade Adolescents, Susan Gordon Williams Jan 2015

Stress, Bullying, Cortisol, And Depresive Symptoms In 9th Grade Adolescents, Susan Gordon Williams

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ABSTRACT Stress and bullying are known contributors to depressive symptoms in adolescents. Prevalence of depressive symptoms in adolescents is estimated to range from13% to 34% in recent studies. Ninth graders are in a transitional period developmentally,biologically, physically, and psychosocially. Few studies have examined the relationship between stress, bullying, and depressive symptoms from a biobehavioral perspective in 9th graders. The purpose of this study was to examine stress, bullying, and depressive symptoms including a biomarker of stress, salivary cortisol diurnal rhythm, to determine if there is mediation between the individual variables of stressful life events, perceivedstress, bullying, and depressive symptoms. The …

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Exploring The Effects Of Direct Contact Compression On Osteogenesis, Shannel Wright Jan 2015

Exploring The Effects Of Direct Contact Compression On Osteogenesis, Shannel Wright

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Clinically, the concept of bone building being the result of mechanical adaptation in healthy individuals has been accepted since Wollf’s Law in 1892. Despite many attempts to understand this mechanism, very little is known about the role mechanical forces play on bone molecularly. Current biomechanical theory supports the concept of osteocytes and bone lining cells creating a three-dimensional network that provides biochemical signaling as a result of mechanical loading. With pressure gradient and interstitial fluid flow models being used as methods of mechanical loading, yet there are still unanswered questions about the validity of both models. The suggested solution lies …

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Nonsense Suppression In A Cftr Mouse Model And Analysis Of Animo Acids Inserted At Cftr Premature Termination Codons In Mammalian Cells, Xiaojiao Xue Jan 2015

Nonsense Suppression In A Cftr Mouse Model And Analysis Of Animo Acids Inserted At Cftr Premature Termination Codons In Mammalian Cells, Xiaojiao Xue

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A nonsense mutation introduces a premature terminations codon (PTC) into an open reading frame (ORF) upstream of a normal stop codon and results in truncated protein production. In frame PTCs account for ~11% of all mutations that cause human genetic diseases. To treat PTC-associated disorders, one approach is to use drugs that facilitate the insertion of amino acids carried by near-cognate aminoacyl-tRNAs at PTCs. Aminoglycosides were shown to suppress nonsense mutations and restore full-length protein production. This process is also termed as readthrough. However, their low efficiency and their potential to induce ototoxicity and nephrotoxicity limits their long-term application for …

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Domain Interactions And Structural Cooperativity In Two Classes Of Drug Targets Investigated By Differential Scanning Calorimetry: I. Abc Transporters: Cystic Fibrosis Transmembrane Conductance Regulator And P-Glycoprotein; Ii. Bacillus Subtilis Nad+Synthetase., Zhengrong Yang Jan 2015

Domain Interactions And Structural Cooperativity In Two Classes Of Drug Targets Investigated By Differential Scanning Calorimetry: I. Abc Transporters: Cystic Fibrosis Transmembrane Conductance Regulator And P-Glycoprotein; Ii. Bacillus Subtilis Nad+Synthetase., Zhengrong Yang

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PART I. Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) cause the lethal genetic disease cystic fibrosis (CF). The most common CF-causing mutation is the deletion of F508 (F508del) in its N-terminal nucleotide binding domain (NBD1), which causes CFTR misfolding and premature degradation. By studying the in vitro thermal unfolding of the isolated NBD1 ± F508del using differential scanning calorimetry (DSC), we show that F508del significantly reduces the thermodynamic and kinetic stability of NBD1. We propose that the non-native contact between the partially denatured F508del-NBD1 and other domains may cause the misfolding of F508del-CFTR. This work …

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Computational Studies On Alpha-Synuclein In Explicit Solvent: Implications In Parkinson’S Disease, Hongyi Yang Jan 2015

Computational Studies On Alpha-Synuclein In Explicit Solvent: Implications In Parkinson’S Disease, Hongyi Yang

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α-Synuclein (αS) is a cytosolic protein expressed at high levels in the human brain and concentrated in presynaptic nerve terminals. Although the precise nature of αS in vivo remains unclear, the aggregation of αS, from its soluble, functional forms into highly organized amyloid fibrils, has been substantially implicated in the pathology of a number of neurodegenerative diseases collectively known as synucleinopathies. The long-term goal of this project is to understand the molecular mechanisms that initiate αS oligomerization in aqueous solution. A novel computational methodology involving protein modeling and atomistic molecular dynamics (MD) simulations is used in this work. The objective …

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Socs3 Deficiency In Myeloid Cells Promotes Tumor Development, Hao Yu Jan 2015

Socs3 Deficiency In Myeloid Cells Promotes Tumor Development, Hao Yu

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STAT3 signaling is a major intrinsic pathway for cancer inflammation owing to its frequent activation in malignant cells, and key role in regulating many genes crucial for inflammation in the tumor microenvironment. Persistently activated STAT3 increases tumor cell proliferation, survival, and invasion while suppressing anti-tumor immunity. Suppressor Of Cytokine Signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway, and generally function as tumor suppressors. The absence of SOCS3 in particular leads to heightened activation of the STAT3 transcription factor. In the present study, we demonstrate that genetic deletion of SOCS3 specifically in myeloid cells significantly enhances tumor growth, which …

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Orientalism Redux: Inci Eviner’S Harem, Pinar Zararsiz Jan 2015

Orientalism Redux: Inci Eviner’S Harem, Pinar Zararsiz

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ORIENTALISM REDUX: INCI EVINER’S HAREM PINAR ZARARSIZ (ART HISTORY) ABSTRACT This thesis examines the 2009 video Harem by Turkish artist Inci Eviner (b. 1956). Eviner’s work centralizes issues of gender in Turkish culture, the history of colonialism, and how historical location informs society at large. Eviner lives and works in Turkey, but exhibits internationally. Harem has been exhibited in Turkey, France, and England. Harem is based on a series of nineteenth-century Orientalist engravings by Antoine Ignace Melling, entitled Intérieur d'une partie du Harem du Grand-Seigneur (Interior of Part of the Harem of the Grand Signor) (1803-1819). Melling’s Harem du Grand-Seigneur …

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Nanostructured Multilayer Hydrogels Of Regulated Architecture: Synthesis And Stimuli-Responsive Properties, Oleksandra Zavgorodnya Jan 2015

Nanostructured Multilayer Hydrogels Of Regulated Architecture: Synthesis And Stimuli-Responsive Properties, Oleksandra Zavgorodnya

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Ultrathin temperature-responsive hydrogels offer fast (in a matter of seconds) response to external stimuli and precise control over the hydrogel composition that has proven to be extremely important for bio-related applications and sensing. These hydrogels can typically uptake ~ 90% of water by volume and are capable of drastic and reversible volume change in response to applied stimuli which makes them ideal candidates to host and deliver small molecules and proteins. The multilayer hydrogels are fabricated by first covalently cross-linking hydrogen-bonded layer-by-layer (LBL) films that serve as templates for hydrogel assembly. This is followed by release of the uncross-linked polymers …

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Functional Role Of Mepe In Tooth Mineralization: Mediation By Tgf-Beta1, Angela Gullard Jan 2015

Functional Role Of Mepe In Tooth Mineralization: Mediation By Tgf-Beta1, Angela Gullard

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Transforming growth factor-β1 (TGF-β1) is one of the most abundant cytokines of the dentin-pulp complex that regulates a broad range of biological processes related to matrix synthesis and ultimately tooth formation, including secretion and mineralization of the dentin extracellular matrix (DECM). TGF-β1 mediates odontoblast cytodifferentiation from precursor dental pulp cells, being up-regulated in odontoblasts and then incorporated into the DECM as a reservoir that can be utilized in times of mechanical, chemical, or bacterial insult. Formation of the DECM is modulated by the actions of small integrin-binding ligand N-linked glycoproteins (SIBLINGs), which include DMP-1, DSPP, BSP, SPP1, and MEPE, with …

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