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A Bioinformatics Approach To Understanding The Pathogenesis Of Ectopic Spine Calcification, Fang Chi Wang
A Bioinformatics Approach To Understanding The Pathogenesis Of Ectopic Spine Calcification, Fang Chi Wang
Electronic Thesis and Dissertation Repository
This study used mice lacking equilibrative nucleoside transporter 1 (ENT1-/-) as a preclinical model to study pathogenesis of ectopic spine mineralization in diffuse idiopathic skeletal hyperostosis (DISH). We hypothesized that mineralization of the annulus fibrosus (AF), was driven by dysregulation of cellular processes and pathways associated with apoptosis, S100A9 proteins, the PI3K-Akt pathway, and lipid metabolism. Target pathways and processes were assessed using in situ localization and quantitative analyses. Metabolomic analysis of AF and plasma data was conducted to identify altered metabolites. Results demonstrate increased caspase-3 activity in the AF of ENT1-/- mice at both timepoints …
The Roles Of Fabp3 In Endothelial Dysfunction And The Transcriptomic Insights Into Cardiovascular Disease, Chi Hien Nguyen
The Roles Of Fabp3 In Endothelial Dysfunction And The Transcriptomic Insights Into Cardiovascular Disease, Chi Hien Nguyen
Electronic Thesis and Dissertation Repository
Heart-type fatty acid binding protein (FABP3) is an effective biomarker for cardiac injuries. However, it has also been tested as a biomarker in patients with peripheral artery diseases; these conditions are complications of atherosclerosis, which is driven by endothelial dysfunction. As FABP3 release is not exclusive to the heart but appears to characterize cardiovascular events, whether FABP3 influences endothelial function is not known. Additionally, the transcriptomic profiles of endothelial cells during cardiovascular stresses remain under-investigated. This thesis investigates the multifaceted role of FABP3 and the transcriptomic alterations in endothelial cells under different cardiovascular stressors, offering novel insights into endothelial dysfunction …
Identification And Characterization Of Isoflavone Reductase Family Members In Soybean, Negin Azizkhani
Identification And Characterization Of Isoflavone Reductase Family Members In Soybean, Negin Azizkhani
Electronic Thesis and Dissertation Repository
Soybean’s yield is threatened by Phytophthora sojae, a pathogen responsible for stem and root rot disease. Glyceollins, unique antimicrobial agents specific to soybeans in partially preventing P. sojae infection, are derived from the isoflavonoid branch of the general phenylpropanoid pathway. One pivotal enzyme exclusively involved in glyceollin synthesis in soybean is the isoflavone reductase (GmIFR), which catalyzes the 2'-hydroxydaidzein conversion to 2'-hydroxy-2,3-dihydrodaidzein as a precursor for glyceollin biosynthesis. To comprehensively identify all members of the GmIFR gene family within the soybean genome, keyword and blast protein searches were conducted, identifying 98 putative GmIFRs. Among these candidates, …
Characterizing Hypoxia, Neutrophil Persistence And Revascularization In The Murine Db/Db Model Of Type Ii Diabetic Impaired Skin Healing, Michael R. Grynyshyn
Characterizing Hypoxia, Neutrophil Persistence And Revascularization In The Murine Db/Db Model Of Type Ii Diabetic Impaired Skin Healing, Michael R. Grynyshyn
Electronic Thesis and Dissertation Repository
Impaired skin healing represents a significant clinical burden. In the diabetic, inflammatory aberrations, hypoxia and insufficient angiogenesis all result in negative wound healing outcomes - repeated infections, poor perfusion and ultimately amputation. Previous research has reported comparable levels of neutrophils in closed wounds up to 4-12 weeks old. Our study interest was in investigating the dynamics of hypoxia resolution, neutrophil persistence and angiogenic response in the db/db model. Contrary to our hypothesis, we observed significantly higher hypoxic load in the wild types at days 3 and 7. Additionally, we observed significantly elevated neutrophil numbers at day 7 db/db wound bed …
Sufu In Shh Signalling Mediated Myogenesis, Suleyman Abdullah
Sufu In Shh Signalling Mediated Myogenesis, Suleyman Abdullah
Electronic Thesis and Dissertation Repository
Myogenesis is defined as the formation of skeletal muscle tissue during embryonic development and involves a multitude of cellular signalling pathways. Among these include the Sonic hedgehog (Shh) signalling pathway which must be deactivated for differentiation into muscle cells to occur. However, less is known regarding the pathways operation during cell differentiation and whether Suppressor of Fused (SUFU), the protein inhibitor of Shh signalling, plays a role. To address this, mouse C2C12 myoblast cells were utilized as a model and differentiated into muscle cells to identify the presence of SUFU during this time. Experiments in qRT-PCR show a decrease in …
The Adaptor Protein P66shc Governs Central Nervous System Cell Metabolism And Resistance To Aβ Toxicity, Asad Lone
Electronic Thesis and Dissertation Repository
Alzheimer’s disease (AD), a progressive and irreversible neurodegenerative disorder, and is the leading cause of dementia worldwide. It has been posited that AD is caused by the gradual deposition of toxic amyloid-b (Ab) plaques in the brain- that cause oxidative stress and eventually leads to neuronal death and synaptic loss. However, multiple therapies that either interfere with the production, or enhance the removal of Ab from the brain, have ultimately failed to slow or prevent AD. With the ever-increasing burden of AD worldwide, there exists an urgent need for novel therapeutic targets. The adult human brain is an energy demanding …
Selective Activation Of Thrombin Activatable Fibrinolysis Inhibitor (Tafi) Attenuates Metastatic And Angiogenic Capabilities Of Melanoma And Lung Carcinoma In Vitro, Jacklyn Krizsan
Electronic Thesis and Dissertation Repository
Metastasis and angiogenesis are hallmarks of aggressive cancers, both depending on degradation of extracellular matrix by proteases such as plasmin. Plasmin activation is inhibited by thrombin-activatable fibrinolysis inhibitor (TAFI)-mediated cleavage of terminal lysine residues on plasminogen receptors. Activation of TAFI is most effectively done in complex with thrombomodulin (TM). TM is known to have anti-cancer properties, but it is not known if this is due to TAFI activation or an alternative substrate protein C (PC). We hypothesize that specific promotion of TAFI activation with TM treatment will attenuate metastatic and angiogenic capabilities of tumour cells.
Melanoma and lung carcinoma cells …
Elucidating The Biomechanics Of Mertk-Mediated Efferocytosis, Brandon Hayato Dickson
Elucidating The Biomechanics Of Mertk-Mediated Efferocytosis, Brandon Hayato Dickson
Electronic Thesis and Dissertation Repository
Macrophages are key mediators of efferocytosis – the phagocytic engulfment and removal of apoptotic cells. During engulfment, the coordinated activity of efferocytic receptors induces the remodeling of the actin cytoskeleton, which facilitates the envelopment of the cell by the plasma membrane. Mer receptor tyrosine kinase (MERTK) is a crucial efferocytic receptor, but its role during actin remodeling is not well understood. Previously, our lab showed that MERTK is an activator of β2 integrins – which are comprised of receptors known to induce the actin polymerization that is required for engulfment. We hypothesized that MERTK is an indirect stimulator of …
Recovery From Social Isolation In Drosophila: The Role Of Dopamine And The Autism-Related Gene Nlg3., Ryley T. Yost
Recovery From Social Isolation In Drosophila: The Role Of Dopamine And The Autism-Related Gene Nlg3., Ryley T. Yost
Electronic Thesis and Dissertation Repository
Within a group, individuals establish their preferred distance from each other, or social space, a form of social behaviour. The resulting distance depends on the exchange of social cues from others that needs to be perceived and integrated within the organism’s neural circuitry. In humans, social spacing can be impaired in neuropsychiatric disorders such as autism and schizophrenia. When organisms are subject to social isolation, profound changes in social behaviour are observed in a variety of species from insects to mammals, including social space. However, the genetic and molecular mechanisms modulating a behavioural response to isolation and possible recovery remain …
Effects Of High Glucose On Autophagy And Apoptosis In Preimplantation Mouse Embryo Culture, Virginia Wolfe
Effects Of High Glucose On Autophagy And Apoptosis In Preimplantation Mouse Embryo Culture, Virginia Wolfe
Electronic Thesis and Dissertation Repository
Maternal diabetes increases congenital malformations due to teratogenic effects of glucose on the developing embryo. High glucose culture alters preimplantation embryo development and is associated with increased oxidative stress. Apoptosis and autophagy are programmed cell death and survival mechanisms induced by oxidative stress, but their role in preimplantation diabetic embryopathy is poorly elucidated. It was hypothesized that high glucose culture would alter autophagic and apoptotic responses, and that they are dependent on the timing of high glucose culture initiation. Embryos were cultured with 0.2 mM (control) or 25 mM (high glucose) of D-glucose starting from the early (36 hpi) or …
Chromatin Regulation By Rb-Interacting Proteins In Cellular Immune Functions, Seung June Kim
Chromatin Regulation By Rb-Interacting Proteins In Cellular Immune Functions, Seung June Kim
Electronic Thesis and Dissertation Repository
The retinoblastoma protein (RB) is historically known for its function in cell cycle control. However, mice carrying targeted Rb1 mutations have revealed that RB serves various non-cell cycle control roles. Notably, RB acts as a scaffold that recruits chromatin regulatory proteins, condensin II and enhancer of zeste homolog 2 (EZH2). These complexes protect the genome integrity through maintaining proper chromosome condensation, long range contacts, and transcriptionally repressive histone modification. This thesis explores the mechanistic links that regulate such RB-condensin II complex or that are leveraged upon pharmacological inhibition of the RB-EZH2 complex. First, I identified potential phosphorylation sites in the …
Regulation Of Hedgehog And Wnt Signaling In Neural Differentiation Of P19 Embryonal Carcinoma Cells, Danielle Margaret Spice
Regulation Of Hedgehog And Wnt Signaling In Neural Differentiation Of P19 Embryonal Carcinoma Cells, Danielle Margaret Spice
Electronic Thesis and Dissertation Repository
The Hedgehog (Hh) and Wnt protein signaling pathways are essential in the differentiation of neurons and astrocytes. As there are many known and new players involved in regulating these pathways, the role of the regulators Suppressor of Fused (SUFU) and Never in Mitosis Kinase 2 (Nek2) have either not been previously reported or have not been thoroughly explored. To address this shortfall CRISPR gene editing was used to target SUFU and Nek2 in the mouse P19 embryonal carcinoma cell model of neural differentiation. Hh and Wnt signaling were explored in normal P19 neural differentiation, which occurs in the presence of …
Tracing The Fate Of Cytokeratin 19+ Cells During Beta Cell Regeneration Stimulated By Multipotent Stromal Cell-Secreted Effectors, Nazihah Rasiwala
Tracing The Fate Of Cytokeratin 19+ Cells During Beta Cell Regeneration Stimulated By Multipotent Stromal Cell-Secreted Effectors, Nazihah Rasiwala
Electronic Thesis and Dissertation Repository
Human bone marrow-derived multipotent stromal cells expanded under Wnt pathway stimulation secrete beta cell-regenerative factors collected as conditioned media (Wnt+ CdM). We used the cytokeratin 19 (CK19)-CreERT Rosa26-mTomato lineage tracing mouse to observe CK19+ cell conversion to insulin+ beta cells following intra-pancreatic injection of Wnt+ CdM. Tamoxifen treatment in mice induced labelling of CK19+ ductal and acinar cells with tdTomato and streptozotocin (50 mg/kg/day x 5 days) induced hyperglycemia. Injection of Wnt+ CdM preserved beta cell mass, reduced non-fasted blood glucose levels, and improved glucose tolerance over a 28-day period compared to controls. Insulin+/tdTomato+ cells in mice given Wnt+ CdM …
Rhamm As A Biomarker And Therapeutic Target In Triple-Negative Breast Cancer, Britney Messam
Rhamm As A Biomarker And Therapeutic Target In Triple-Negative Breast Cancer, Britney Messam
Electronic Thesis and Dissertation Repository
Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours characterized by early metastases and poor prognosis. Discovering novel biomarkers and therapeutic targets is necessary to improve TNBC patient outcomes as resistance to chemotherapy, the main therapeutic approach for TNBC, is common. In my study, RHAMM promoted proliferation of TNBC MDA-MB-231 tumour cells. RHAMM expression increased sensitivity to doxorubicin (p=0.0002) and strongly increased sensitivity to the FDA-approved MEK1/2 inhibitor trametinib (p≤0.0001). Doxorubicin and trametinib selectively killed RHAMM+/+ MDA-MB-231 tumour cells grown as co-cultures with RHAMM-/- MDA-MB-231 tumour cells. RHAMM-loss or trametinib decreased phosphorylated ERK1/2 protein levels and …
Localization And Function Of Pannexin2 Isoform 202, Marina D. Sertsis
Localization And Function Of Pannexin2 Isoform 202, Marina D. Sertsis
Electronic Thesis and Dissertation Repository
Pannexins (PANX) are a family of membrane glycoproteins comprised of 3 members: pannexin 1 (PANX1), pannexin 2 (PANX2), and pannexin 3 (PANX3). Oligomerized pannexin proteins form channels that allow for the passage of ions and small molecules. While PANX1 and PANX3 mostly localize to the cell surface, PANX2 remains intracellular within the endoplasmic reticulum (ER). Recently, a splice variant of PANX2 termed Panx2-202, was detected during development of murine skin. However, the localization and function of this shorter Panx2-202 isoform remains unknown. We found that Panx2-202 localizes to the ER in immortalized rat epidermal keratinocytes. We also found that expression …
Extrinsic And Intrinsic Factors Influencing Homeostasis And Repair In Oral Tissues, Georgia Nikoloudaki
Extrinsic And Intrinsic Factors Influencing Homeostasis And Repair In Oral Tissues, Georgia Nikoloudaki
Electronic Thesis and Dissertation Repository
The oral tissues, including gingiva and buccal mucosa, heal rapidly with minimal scar formation. Although in the oral cavity, the palatal mucosa is associated with excessive scarring in response to injury. In this thesis, first, I investigated the complex relationship between cells and their microenvironment using wound healing models in which extracellular matrix composition and mechanical stiffness affect cellular responses during acute wound repair. I also determined how intrinsic differences of cells recruited during healing contribute to wound resolution.
In Chapter 2, I first investigated cell-extrinsic factors, specifically the influence of the pro-fibrotic matricellular protein periostin on palatal healing. Using …
The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams
The Role Of Reactive Oxygen Species In The Accumulation Of Driver Mutations In B Cell Acute Lymphoblastic Leukemia, Mia P. Sams
Electronic Thesis and Dissertation Repository
B cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with recurrent mutations and high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine was tested for its ability to prolong lifespan of a mouse model of B-ALL and reduce frequency of mutations. Mice treated with 1g/L of N-acetylcysteine in drinking water were found to have delayed onset of B-ALL at 11 weeks of age and changes in gene expression relating to B cell development, calcium-apoptosis signaling, and pathways in cancer, although no differences in lifespan were observed. Tumours from treated …
Characterization Of Galectin-16 Expression And Function In Placental Cells, Jennifer Kaminker
Characterization Of Galectin-16 Expression And Function In Placental Cells, Jennifer Kaminker
Electronic Thesis and Dissertation Repository
The processes of cellular differentiation and apoptosis are critical for placental development. The galectin-16 gene (LGALS16) is associated with these processes in the placenta, but the mechanism by which it acts is poorly characterized. My bioinformatics analysis revealed that LGALS16 expression was limited to specific tissues including the placenta and identified multiple regulatory molecules (transcription factors and miRNAs), which could potentially control relevant transcriptional and post-transcriptional mechanisms. Considering the predominant expression of LGALS16 in placenta, I examined the expression, regulation, and function of LGALS16 in BeWo and JEG-3 cell lines representing in vitro models of trophoblast differentiation. In …
The Effect Of Maternal Immune Activation On Placental And Fetal Development In Rats, Kelly J. Baines
The Effect Of Maternal Immune Activation On Placental And Fetal Development In Rats, Kelly J. Baines
Electronic Thesis and Dissertation Repository
Development of the placenta and embryo is a highly orchestrated process that is vulnerable to changes in the in utero environment. Maternal immune activation (MIA) during pregnancy is a major risk factor for many obstetric complications and predisposes offspring to growth restriction as well as cognitive and neurobehavioral deficits; however, the mechanisms underlying these risks remain unknown. In this thesis, I aimed to determine the effect of MIA on development of the placenta and fetal brain. By administering the viral mimetic polyinosinic:polycytidylic acid to pregnant rats as a model of MIA, I demonstrated that a maternal antiviral response is associated …
Illuminating Transfer Rna Variants As Genetic Modifiers In Models Of Human Disease, Jeremy T. Lant
Illuminating Transfer Rna Variants As Genetic Modifiers In Models Of Human Disease, Jeremy T. Lant
Electronic Thesis and Dissertation Repository
Transfer RNAs (tRNAs) physically link the genetic code to an amino acid sequence, by recruiting amino acids to three-nucleotide codons in messenger RNAs. To ensure that the genetic code is translated as intended, tRNAs must be accurately aminoacylated and faithfully recognize codons in the ribosome during protein synthesis. Given the critical function of tRNAs, it has often been assumed that mutations in human tRNA genes would be either lethal to cells or not significantly impair tRNA function. My goal was to rigorously test this assumption in mammalian cell models, prompted by the recent discovery of unprecedented variation in human tRNA …
Connexin 43 Contributes To Phenotypic Variability Of The Mouse Skull, Elizabeth Jewlal
Connexin 43 Contributes To Phenotypic Variability Of The Mouse Skull, Elizabeth Jewlal
Electronic Thesis and Dissertation Repository
The purpose of this study was to determine whether connexin 43 (Cx43) contributes to craniofacial phenotypic variability. Skull shape and variation were compared within and among two heterozygous mutant mouse models (G60S/+ and I130T/+) that exhibit different levels of Cx43 channel function when compared to their wildtype counterparts (~80% and ~50% reduction in function, respectively). Results indicated mutants have significant differences in skull shape compared to wildtype littermates. Similar patterns of shape difference were found in both mutants. Increased skull shape variation and a disruption in the covariation of skull structures were observed in G60S/+ mutants only. These results show …
Spatiotemporal Characterization Of The Prr12 Paralogues In Zebrafish, Renee Jeannine Resendes
Spatiotemporal Characterization Of The Prr12 Paralogues In Zebrafish, Renee Jeannine Resendes
Electronic Thesis and Dissertation Repository
Pathogenic variants in the human PRR12 (Proline Rich 12) gene are associated with PRR12-related Neuroocular Syndrome. However, little is known about the gene/protein function. The zebrafish was utilized to address this, as its attributes place it as a premier model to study genes involved in human development and disease. In situ hybridization and RT-PCR of embryos and larvae, and qRT-PCR of adult tissues revealed the spatial and temporal distributions of the prr12 paralogues: prr12a and prr12b. Both paralogues were detected from the maternal and zygotic transcriptomes in a global and diffuse expression pattern, and there was enrichment …
Understanding The Kinomic Contributions To Tyrosine Kinase Inhibitor Resistance In Triple Negative Breast Cancer, Cory Lefebvre
Understanding The Kinomic Contributions To Tyrosine Kinase Inhibitor Resistance In Triple Negative Breast Cancer, Cory Lefebvre
Electronic Thesis and Dissertation Repository
Resistance to tyrosine kinase inhibitors (TKIs) presents a growing challenge in the development of therapeutic targets for cancers such as triple negative breast cancer (TNBC), where conventional therapies are ineffective at combatting systemic disease. Potential targets in TNBC include the receptor tyrosine kinases EGFR (epidermal growth factor receptor) and c-Met, however, targeted anti-EGFR and anti-c-Met therapies have faced challenges in clinical trials due to acquired resistance. We hypothesize that response versus resistance of triple negative breast cancer to the tyrosine kinase inhibitors erlotinib and cabozantinib is mediated by compensatory changes in the kinome and phosphoproteome. To test this, we (1) …
Metabolic Regulation During Extraembryonic Endoderm Differentiation, Mohamed Gatie
Metabolic Regulation During Extraembryonic Endoderm Differentiation, Mohamed Gatie
Electronic Thesis and Dissertation Repository
The inner cell mass undergoes orchestrated cellular divisions resulting in the formation of the epiblast (EPI) and primitive endoderm (PrE). Understanding the process of cell fate specification is crucial to appreciate the intricacies of proper embryonic development. While the mouse embryo is an excellent model, limitations do exist with number, technical challenges, and accessibility, therefore, in my thesis I employed two cell-based models to recapitulate the EPI-PrE fate in vitro. Many signaling pathways have been implicated in this lineage decision, metabolism and its downstream products have been recently regarded as a driver of lineage commitment. Using various biochemical, molecular, …
Kindlin-1 Is Involved In Spreading, Migration, And Protein Regulation In Epidermal Scc-13 Cells, Naomi Mishan
Kindlin-1 Is Involved In Spreading, Migration, And Protein Regulation In Epidermal Scc-13 Cells, Naomi Mishan
Electronic Thesis and Dissertation Repository
Kindlin-1 is a scaffold protein linking the cytoskeleton to the extracellular matrix. Loss of function mutations in the FERMT1 gene (encoding Kindlin-1) cause gastrointestinal and skin defects associated with increased susceptibility to aggressive epidermal squamous cell carcinoma (SCC). This study investigated the consequences of targeted FERMT1 inactivation in the SCC-13 cell line of epidermal SCC. My studies demonstrate Kindlin-1 is not essential for SCC-13 proliferation or clonogenic potential in culture. Kindlin-1 was required for cell spreading on collagen I, but not on laminin-332, and its absence enhanced SCC-13 directional migration. Finally, I identified several proteins involved in tumor formation and …
Insights Into O-Glcnac-Mediated Regulation Of Galectin Expression And Secretion In Promyelocytic Hl-60 Cells, Adam J. Mctague
Insights Into O-Glcnac-Mediated Regulation Of Galectin Expression And Secretion In Promyelocytic Hl-60 Cells, Adam J. Mctague
Electronic Thesis and Dissertation Repository
Galectins are a family of -galactoside-binding proteins involved in cell stress responses and differentiation. Galectins are multifunctional proteins widely studied in many cell models including acute myeloid leukemia HL-60 cells where they mediate numerous intra- and extracellular functions in response to many stress-inducing stimuli. O-GlcNAcylation is a dynamic post-translational modification implicated in the regulation of many cellular diseases including cancers. The O-GlcNAc mediated expression and secretion of galectins during neutrophilic differentiation was examined in HL-60 cells. Galectin gene (LGALS), galectin protein expression, and galectin secretion were determined by RT-qPCR, immunoblotting, and ELISA, respectively. Inhibition of O-GlcNAcylation induced markers of differentiation …
Free Fatty Acid Treatment Alters Autophagy During Mouse Preimplantation Embryo Development, Zuleika C. L. Leung
Free Fatty Acid Treatment Alters Autophagy During Mouse Preimplantation Embryo Development, Zuleika C. L. Leung
Electronic Thesis and Dissertation Repository
Obesity-induced hyperlipidemia is one of the main factors for female infertility. Hyperlipidemia, specifically with high levels of palmitic acid (PA) and oleic acid (OA), interferes with preimplantation development. Autophagy is essential in early embryo development but, it is unknown whether hyperlipidemia affects autophagic mechanisms in preimplantation embryos. It was hypothesized that PA will alter autophagy in preimplantation mouse embryos and that the subsequent effects will be reversed by OA. PA impaired blastocyst development by arresting embryos at the 8-cell stage. PA also elevated early embryo autophagy by increasing autophagosome formation, decreasing maturation, and disrupting degradation. Co-treatment with OA showed developmental …
Investigation Of Β5 Integrin Function In Epithelial Ovarian Cancer Cell Adhesion And Metastatic Properties Of Spheroids, Dolly Dhaliwal
Investigation Of Β5 Integrin Function In Epithelial Ovarian Cancer Cell Adhesion And Metastatic Properties Of Spheroids, Dolly Dhaliwal
Electronic Thesis and Dissertation Repository
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy in the developed world. EOC metastasis is unique since malignant cells detach directly from the primary tumor site into the abdominal fluid and form multicellular aggregates, called spheroids, that possess enhanced survival mechanisms while in suspension. As such, altered cell adhesion properties are paramount to EOC metastasis with cell detachment from the primary tumor, dissemination as spheroids, and reattachment to peritoneal surfaces for secondary tumor formation. These interactions play a crucial role in cell-cell and cell-extracellular matrix interactions, having implications in multiple steps of cancer progression. We previously showed that …
The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo
The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo
Electronic Thesis and Dissertation Repository
Pannexins (PANX1, 2, 3) are a family of channel-forming glycoproteins that mediate intracellular and paracrine signaling. In contrast to PANX2, PANX1 has been extensively investigated in the skin, modulating cell differentiation, wound healing, and melanoma development. PANX1 and PANX2 can co-exist in the same cell and form mixed channels where their glycosylation seems to regulate their intermixing. N-glycosylation and caspase cleavage have been proposed as modulators of the function of PANX1, but their effects on PANX2 are unknown. We explored the PANX2 expression in mouse skin and showed that a Panx2 splice variant (PANX2-202) is continuously expressed throughout aging skin. …
Maternal Lifelong Western Diet Consumption Impacts Placental And Brain Development In The Term Guinea Pig Fetus, Carlene H. Cihosky
Maternal Lifelong Western Diet Consumption Impacts Placental And Brain Development In The Term Guinea Pig Fetus, Carlene H. Cihosky
Electronic Thesis and Dissertation Repository
Both metabolic and cognitive dysfunction can originate from fetal reprogramming precipitating from adverse conditions experienced in utero. Of note is the western diet (WD), which is associated with maternal energy imbalances that may hinder fetal development through altered placental function. Brain-derived neurotrophic factor (BDNF), a growth factor that supports the placenta and developing brain, is responsive to such energy imbalances. This study sought to investigate the impact of lifelong maternal WD consumption on fetoplacental development, focusing on relations between placental changes, and fetal growth and neurodevelopment in a guinea pig model. Maternal WD consumption resulting in a lean metabolically …