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Articles 1 - 11 of 11
Full-Text Articles in Life Sciences
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 …
Modelling Prenatal Hypoxia As A Risk Factor For Schizophrenia Vulnerability In Patient-Derived Cerebral Organoids, Dana M. Gummerson
Modelling Prenatal Hypoxia As A Risk Factor For Schizophrenia Vulnerability In Patient-Derived Cerebral Organoids, Dana M. Gummerson
Electronic Thesis and Dissertation Repository
Prenatal hypoxia during fetal development is a significant environmental risk factor linked to schizophrenia (SCZ) vulnerability. However, hypoxia’s impact on human brain development at the cellular level remains unclear. Our laboratory has developed human cerebral organoids using induced pluripotent stem cells (iPSCs) derived from healthy control or SCZ patient cell lines to address these questions. This creates a platform that allows for the investigation into the pathophysiology of SCZ and hypoxia in tandem. Organoids were exposed to hypoxic conditions at one month of development, mimicking the early stages of cortical growth in the human fetus. Results reveal innate differences in …
Nutrient Sensing Pathways Mediating Igfbp1 Phosphorylation In Fgr, Shapnil Bhuiyan
Nutrient Sensing Pathways Mediating Igfbp1 Phosphorylation In Fgr, Shapnil Bhuiyan
Electronic Thesis and Dissertation Repository
Impairment of fetal oxygen levels and nutrient delivery contributes to fetal growth restriction (FGR), which affects 20% of pregnancies. Such cellular stress induces hepatic Insulin-like Growth Factor Binding Protein 1 (IGFBP1) phosphorylation, which sequesters Insulin-like Growth Factor 1 (IGF-I) and markedly reduces fetal growth signaling. IGFBP1 hyperphosphoryaltion in hypoxia is mediated through the mTOR signaling pathway and through the Amino Acid Response (AAR) pathway during amino acid deprivation. Hypoxia stimulates upstream mTORC1 regulators, AMPK and REDD1 which are well-established upstream regulators of one of the two mTOR complexes, mTORC1. The molecular mechanisms by which upstream mTORC1-driven processes regulate IGFBP1 phosphorylation …
Translational Control Of Stress Induced Breast Cancer Plasticity, Michael Jewer
Translational Control Of Stress Induced Breast Cancer Plasticity, Michael Jewer
Electronic Thesis and Dissertation Repository
Cancer cell plasticity, whereby stem-cell-like properties are acquired in response to stress, represents a major challenge in cancer treatment. Using cell line and patient-derived xenograft (PDX) models, we demonstrate that translational reprogramming occurs in response to stresses such as hypoxia and chemotherapy which elicits stem cell properties in breast cancer. Other stresses like chemotherapy demonstrate the translational inhibition that has been well characterized as an integral hypoxic cellular response. The inhibition of translation is primarily regulated at initiation by mTOR/4E-BP1 and PERK/eIF2α signalling. We identify previously undescribed 5’ untranslated regions (5’UTRs) of plasticity-associated genes like NANOG, SNAIL and NODAL. …
Investigating The Role Of Tp53inp1 And Tp53inp2 In Neuronal Autophagy And Mitophagy, Vidhyasree Shyam
Investigating The Role Of Tp53inp1 And Tp53inp2 In Neuronal Autophagy And Mitophagy, Vidhyasree Shyam
Electronic Thesis and Dissertation Repository
Autophagy is highly conserved cellular process that functions in ensuring the turnover of proteins and organelles in a number of different cell types. Mitophagy is a selective form of autophagy which serves to target and rid the cell of damaged or superfluous mitochondria. The process is central to preventing the accumulation of defective mitochondria and is particularly important in neurons, which rely exclusively on mitochondria to sustain their immense metabolic needs. Dysregulation of autophagy is believed to contribute to the neurodegeneration seen in such disorders as Parkinson’s disease and cerebral ischemia. However, further understanding of the role of neuronal autophagy …
Physiological Resolution Of Periodic Breath Holding During Heavy Intensity Fartlek Exercise, David J. Lim
Physiological Resolution Of Periodic Breath Holding During Heavy Intensity Fartlek Exercise, David J. Lim
Electronic Thesis and Dissertation Repository
The purpose was to compare the physiological responses to periodic 5 s breath holds (CBH), increased power output (FLK), and both (FBH) every 30 s followed by 25 s of continuous heavy intensity cycling exercise with free-breathing (CON). Minute ventilation (V̇ E) was greater (p < 0.05) in CBH (97.58 + 16 L·min-1) and FBH (100.9 + 19 L·min-1), pulmonary oxygen uptake (V̇ O2p) was similar in CBH (2.73 + 0.14 L·min-1) and FBH (2.73 + 0.14 L·min-1) and greater in FLK (2.85 + 0.12 L·min-1), compared to CON (2.71 + 0.12 L·min-1). FBH also resulted in slower V̇ O2p kinetics (62.2 + 19 s) and greater blood lactate concentrations (11.5 + 2.7 mM), compared to CON (48.8 + 12 s; 9.0 + 2.3 mM). Together, we demonstrated that breath hold-induced hypoxemia and hypercapnia were resolved when not combined with additional work.
Maternal Nutrient Restriction In Pregnant Guinea Pigs Impacts Fetal-Placental Growth And Oxygenation, Alexander Elias
Maternal Nutrient Restriction In Pregnant Guinea Pigs Impacts Fetal-Placental Growth And Oxygenation, Alexander Elias
Electronic Thesis and Dissertation Repository
Maternal nutrient restriction (MNR) in guinea pigs results in placental structural abnormalities that reduce nutrient transport contributing to fetal growth restriction (FGR). However, whether fetal oxygenation is also reduced as a further mediator of altered growth and development remains unknown. Guinea pig sows were fed ad libitum (Controls) or 70% of the control diet pre-pregnant switching to 90% at mid-pregnancy (MNR). Animals were necropsied near term for fetal-placental growth measures, blood metabolites, and markers of tissue hypoxia and oxidative stress. MNR resulted in FGR with brains that are large and livers that are small relative to body weight which suggests …
Regulation Of Igfbp-1 Phosphorylation In Hypoxia Via Mtor Signaling, Ian Damerill
Regulation Of Igfbp-1 Phosphorylation In Hypoxia Via Mtor Signaling, Ian Damerill
Electronic Thesis and Dissertation Repository
In this study, we provide novel evidence for a role of fetal liver mTOR signaling in regulating IGF-I bioavailability by modulating IGFBP-1 phosphorylation due to hypoxia – a key factor in the development of reduced fetal growth in utero. We utilized HepG2 cells in vitro and demonstrated a link between mTOR inhibition and hypoxia-induced IGFBP-1 phosphorylation. Using a biological assay for IGF-I receptor autophosphorylation, we demonstrated a functional significance for hypoxia-induced IGFBP-1 phosphorylation in reducing IGF-I bioactivity in vitro. Further, we have implicated a mechanistic link to increased CK2 activity within this regulation. We demonstrate that mTOR inhibition …
Niacin And Microvascular Endothelial Cell Response To Fatty Acid Excess And Hypoxia, Dominic Pang
Niacin And Microvascular Endothelial Cell Response To Fatty Acid Excess And Hypoxia, Dominic Pang
Electronic Thesis and Dissertation Repository
Niacin can reduce vascular disease risk, but its mechanism of action is controversial, and may not be dependent on systemic lipid modifying effects. This thesis tested the hypothesis that niacin directly improves endothelial cell function under lipotoxic and low oxygen conditions, as seen in ischemic conditions during metabolic syndrome, and investigated the potential mechanism involved. Human microvascular endothelial cell (HMVEC) survival was reduced by exposure to excess fatty acids under both normoxic and low oxygen conditions. Angiogenic function, as determined by tube formation on Matrigel, was impaired during fatty acid overload under either normoxic or low oxygen conditions. These effects …
Investigating Microenvironmental Regulation Of Human Chordoma Cell Behaviour, Priya Patel
Investigating Microenvironmental Regulation Of Human Chordoma Cell Behaviour, Priya Patel
Electronic Thesis and Dissertation Repository
The tumor microenvironment is complex and often includes matricellular proteins and regions of hypoxia, which can promote stem and progenitor properties that regulate cancer cell biology. We hypothesized that hypoxia and CCN2 would promote notochord progenitor-like characteristics in human chordoma (U-CH1) cells, and assessed cell phenotype using Real-time qPCR and in vitro functional assays. We found the expression of CCN family members CCN1, CCN2, CCN3 and CCN5 in U-CH1 cells. We demonstrate that hypoxia and CCN2 promoted progenitor-like characteristics specific to the notochordal tissue of origin. Specifically, hypoxia had the greatest ability to promote progenitor characteristics (increase in notochord markers …
Hypoxia-Induced Alterations In Skeletal Muscle Cell Respiration And Resveratrol As A Potential Pharmacological Intervention, Kathleen R. Belgrave
Hypoxia-Induced Alterations In Skeletal Muscle Cell Respiration And Resveratrol As A Potential Pharmacological Intervention, Kathleen R. Belgrave
Electronic Thesis and Dissertation Repository
Using the C2C12 mouse muscle myoblast cell line, I sought to investigate the hypothesis that differentiation under hypoxia impairs muscle mitochondrial respiratory function irreversibly. Resveratrol (RSV) will increase expression of markers of mitochondrial biogenesis and reverse the hypoxia-induced depression of O2 consumption rates. Hypoxia decreased oxygen consumption rates after five days of differentiation and after two days of normoxic recovery. This coincided with a hypoxia-induced decrease in protein levels of the NDUFB8 subunit of complex I of the electron transport chain and decreases in mRNA levels of mitochondrial biogenesis transcription factors, both of which could contribute …