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Natural Genetic Variation Affecting Calcium Homeostasis, Rebecca Anna Replogle

Open Access Dissertations

Calcium (Ca) is essential for multiple functions within the body including skeletal health. The level of Ca in the serum is tightly regulated. During periods of habitual low Ca intake, the body senses a decrease in serum Ca and increases renal conversion of 25 hydroxyvitamin D (25(OH)D) to 1,25 dihydroxyvitamin D (1,25(OH)2D). 1,25(OH)2D acts through the vitamin D receptor (VDR) to increase intestinal Ca absorption, renal Ca reabsorption and skeletal Ca resorption. Efficient intestinal Ca absorption, especially during periods of low Ca intake, is critical for protecting bone mass. Ca absorption and its primary regulator, 1,25(OH)2D, are affected by both …

Store-Operated Calcium Entry And Its Function During Fertilization In Porcine Eggs, Chunmin Wang

Open Access Dissertations

In a variety of mammalian cells, the depletion of intracellular Ca^{2+ stores leads to Ca2+ influx across the plasma membrane though a process known as store-operated Ca2+ entry. It not only plays a critical role in the replenishment of the Ca2+ stores but it is also responsible for the maintenance of long-lasting high intracellular Ca2+ levels and sustaining repetitive Ca2+ oscillations. During fertilization a Ca2+ signal, which can take the form of a single or multiple Ca2+ elevations (depending on the species) is the universal trigger for the egg-to-embryo transition. For sustaining …}

Characterization Of Caxck31, A Bacterial Calcium/Proton Antiporter, Marc Robert Ridilla

Open Access Dissertations

To better understand a class of transporters known as Calcium/Cation Antiporters (CaCAs), the bacterial calcium/proton antiporter CAXCK31 was purified and characterized. New methods were developed for its heterologous overexpression and purification. These methods help to define stress responses to toxic membrane overproduction in E. coli and may be broadly applicable to studies of membrane proteins. The results from a variety of biochemical and biophysical experiments demonstrated that CAXCK31 exists as a dimer in the membrane and can be purified in the dimeric state. The methods used include chemical cross-linking, FRET, and SEC-MALS. In addition, various transport properties of CAXCK31, including …

Er Stress Coupled Pannexin Channel Activation Via Stim Proteins, Ankur Bodalia

Electronic Thesis and Dissertation Repository

Many neurodegenerative diseases, including Alzheimer’s Disease, are associated with ER stress. It is suggested that plasma membrane channels contribute to the increased ionic influx and subsequent cell death in response to ER stress. Pannexin channels, which have been implicated in various pathophysiological conditions, are a suitable candidate for facilitating this response. However, mechanisms of pannexin channel activation are poorly defined. I investigated the potential regulation of pannexin activity by the ER stress sensor, STIM. It was hypothesized that pannexin channel activation during ER stress is contingent on the recruitment of STIM proteins. In neurons, pannexin activation was observed in response …

Calcium Intake Patterns In Association With Demographic And Socioeconomic Factors In Us Population 2-69 Years Of Age: A Cross-Sectional Study, Farah Raoof

Public Health Theses

Background: Calcium is important to various aspects of health and is necessary for life. Inadequate calcium intake has serious consequence on health, such as osteoporosis, impaired muscle and nerve functions and obesity. Similarly, excessive intake is associated with cardiovascular risks and urinary tract stone formation. Therefore a balanced calcium intake is of utmost importance especially knowing that maximum calcium storage potential in bones is reached roughly in late 20s of age and starts gradually declining thereafter.

Objective: The objective of this study is to explore calcium intake patterns in the United States population in association with a number of selected …

Coupling S100a4 To Rhotekin Alters Rho Signaling Output In Breast Cancer Cells, Min Chen, Anne R. Bresnick, Kathleen L. O'Connor

Markey Cancer Center Faculty Publications

Rho signaling is increasingly recognized to contribute to invasion and metastasis. In this study, we discovered that metastasis-associated protein S100A4 interacts with the Rho-binding domain (RBD) of Rhotekin, thus connecting S100A4 to the Rho pathway. Glutathione S-transferase pull-down and immunoprecipitation assays demonstrated that S100A4 specifically and directly binds to Rhotekin RBD, but not the other Rho effector RBDs. S100A4 binding to Rhotekin is calcium-dependent and uses residues distinct from those bound by active Rho. Interestingly, we found that S100A4 and Rhotekin can form a complex with active RhoA. Using RNA interference, we determined that suppression of both S100A4 and …

Post-Injury Calcium Chelation Rescues Skeletal Muscle Regeneration In Mice, Matthew D. Magda

Honors Scholar Theses

During aging the ability of skeletal muscle to regenerate after injury wanes until muscle integrity cannot be maintained. In this study it is shown that calcium chelation can restore young-like regenerative ability in an aged mouse model of skeletal muscle regeneration.

Roles Of Neurotransmitters In The Regulation Of Neuronal Electrical Properties And Growth Cone Motility, Lei Zhong

Biology Dissertations

In addition to acting in synaptic transmission, neurotransmitters have been shown to play roles in the development of nervous system. Developing neurons extend neurites to connect to their target cells, and growth cones at the tip of growing neurites are critical for pathfinding. Although evidence for the regulation of axonal growth and growth cone guidance by neurotransmitters and neuromodulators is emerging, less is known about the mechanisms by which neurotransmitters affect developing neurons. Here, I focus on three neurotransmitters/ neuromodulators and describe their actions (a) at the level of growth cone, especially on filopodia, which serve as sensors that allow …

The Relationship Between Serum 25-Hydroxyvitamin D, Vitamin D And Calcium Intake, And Adiposity In Infants, Carolyn W. Morris

Nutrition Theses

Purpose: National prevalence of childhood overweight and obesity has plateaued in recent years, but rates remain high, with approximately 10% among children“high weight.” The relationship between adiposity and serum 25-hydroxyvitamin D [25(OH)D] status has been well-explored in older individuals, with inconsistent results. Furthermore, previous studies have suggested a relationship between adequate consumption of calcium and vitamin D and healthy weight status in older children and adults. However, in the infant population, there are few studies detailing the interaction between body composition and serum 25(OH)D or intake of calcium and vitamin D. Our study aims were to assess the association between …

Oxidative Stress Disruption Of Receptor-Mediated Calcium Signaling Mechanisms, Tso-Hao Tang, Chiung-Tan Chang, Hsiu-Jen Wang, Joshua Erickson, Rhett A. Reichard, Alexis Martin, Erica Shannon, Adam L. Martin, Yue-Wern Huang, Robert Aronstam

Biological Sciences Faculty Research & Creative Works

Background: Oxidative stress increases the cytosolic content of calcium in the cytoplasm through a combination of effects on calcium pumps, exchangers, channels and binding proteins. In this study, oxidative stress was produced by exposure to tert-butyl hydroperoxide (tBHP); cell viability was assessed using a dye reduction assay; receptor binding was characterized using [³H]N-methylscopolamine ([³H]MS); and cytosolic and luminal endoplasmic reticulum (ER) calcium concentrations ([Ca²⁺]_i and [Ca²⁺]_L, respectively) were measured by fluorescent imaging.

Results: Activation of M3 muscarinic receptors induced a biphasic increase in [Ca²⁺] …

Osmotic Regulation Of The Amphipod Gammarus Chevreuxi (Sexton, 1912), Sam Houston

The Plymouth Student Scientist

This study investigated osmotic regulation in the amphipod, Gammarus chevreuxi, and is the first publication of this organism’s osmotic regulatory curves. Unlike most estuarine amphipods studied to date which are hyperosmotic regulators, G. chevreuxi is a hyper-hyposmotic regulator. The hyperosmotic gradient maintained by G. chevreuxi in dilute media is very low (~120mmol.L-1), which has been interpreted as evidence of freshwater ancestry among the Crustacea. Salinity acclimation did not appear to affect heart rate or pleopod beat frequency. The gill cells responsible for ion uptake appeared to be smaller in high salinities or distorted. The apical membrane in concentrated media shows …

Zona Pellucida-Induced Acrosome Reaction In Human Sperm: Dependency On Activation Of Pertussis Toxin-Sensitive G(I) Protein And Extracellular Calcium, And Priming Effect Of Progesterone And Follicular Fluid., Alessandro Schuffner, Hadley Bastiaan, E. Duran, Zin-Yong Lin, Mahmood Morshedi, Daniel Franken, Sergio Oehninger

Eyup Hakan Duran

In these studies, we aimed to characterize the effects of the physiological, homologous agonists of the acrosome reaction, i.e. the zona pellucida (ZP) and progesterone/follicular fluid, on human sperm. The specific aims of our studies were: (i) to examine the dependency of the solubilized ZP-induced acrosome reaction on G(i) protein activation and presence of extracellular calcium; and (ii) to determine whether progesterone/follicular fluid exert a priming or synergist effect on the solubilized ZP-induced acrosome reaction. Highly motile sperm from fertile donors were exposed to the agonists in a microassay and the acrosomal status of live sperm was determined by indirect …

Regulation Of Trpm2 Channels By Fyn Kinase, Matthew L. Johnston

Electronic Thesis and Dissertation Repository

TRPM2 is a calcium-permeable non-selective cation channel that acts as a mediator of cell death in response to oxidative stress. It has been shown that oxidative stress increases TRPM2 tyrosine phosphorylation and activation – an effect that is blocked by PP2, a non-specific inhibitor of Src family kinases. However, the kinase and target TRPM2 tyrosine residue(s) involved have not yet been identified. Here, we investigated the potential regulation of TRPM2 by Fyn. Intracellular application of recombinant Fyn potentiated TRPM2 currents in HEK293 cells expressing inducible TRPM2 (TRPM2-HEK293 cells). Further, a physical interaction between Fyn and TRPM2 was demonstrated by co-immunoprecipitation …

Increasing Ca2+ Deposition In The Western Us: The Role Of Mineral Aerosols, Janice Brahney, Ashley P. Ballantyne, C. Sievers, Jason C. Neff

Watershed Sciences Faculty Publications

Considerable research has focused on the role of industrial emissions in controlling the acidity of precipitation; however, much less research has focused on the role of mineral aerosols emitted from soils. According to data published by the National Atmospheric Deposition Network (NADP), over the past 17 years Ca2+ deposition has increased over large regions of the US. A trend analysis to determine regions of significant change in Ca2+ deposition revealed statistically significant increases in three broad regions within the western half of the country: the inter-mountain west, the midwest, and the northwest. We evaluated potential changes in sources of calcium …

Genetic Differences Control The Response Of Femur And Lumbar Spine Trabecular Bone Microstructure To Dietary Calcium Restriction In Mice, Xu Lan

College of Health and Human Sciences Honors Program Undergraduate Theses

Both dietary calcium and genetics influence bone density and structure. However, how genetics

affect the adaptation response of bone parameters to dietary calcium (Ca) restriction is unknown.

11 inbred strains of mice were fed adequate (0.5%) or low (0.25%) Ca diets from 4-12 weeks of

age and were evaluated for gene-by-diet interactions affecting bone structure at the femur and

lumbar spine. We observed that genetics and diet main effects as well as gene-by-diet

interactions significantly affected femur trabecular and cortical bone, and lumbar spine

trabecular bone microCT parameters. There were no significant correlations between basal and

adaptation parameters in femur …

Role Of Neurogranin In The Regulation Of Calcium Binding To Calmodulin, Anuja Chandrasekar

Dissertations & Theses (Open Access)

Role of Neurogranin in the regulation of calcium binding to Calmodulin

Anuja Chandrasekar, B.S

Advisor: M. Neal Waxham, Ph.D

The overall goal of my project was to gain a quantitative understanding of how the interaction between two proteins neurogranin (RC3) and calmodulin (CaM) alters a fundamental property of CaM. CaM, has been extensively studied for more than four decades due to its seminal role in almost all biological functions as a calcium signal transducer. Calcium signals in cardiac and neuronal cells are exquisitely precise and enable activation of some processes while down-regulating others. CaM, with its four calcium binding sites, …

The Effects Of Chronic Calcium Dysregulation On Behavioral And Pathological Features Of Alzheimer's Disease, Jonathan Sabbagh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose etiology is unknown. Recent studies have implicated alterations in calcium homeostasis as a pathogenic contributor to AD. Calcium dysregulation has been observed in aged and AD brains, an event which could potentially facilitate the development of multiple pathologies observed in AD. Specifically, disrupting intracellular calcium levels in vitro has been demonstrated to increase amyloid-beta (Aβ) production, tau phosphorylation, and neuronal loss. However, there is a paucity of data on the behavioral and biochemical consequences of chronic in vivo perturbation of calcium homeostasis. In a series of experiments designed to evaluate the …

Vitamin D Plus Calcium Supplementation Among Postmenopausal Women : Effect On Risk Of Heart Failure In The Women's Health Initiative., Macarius Mwinisungee Donneyong

Electronic Theses and Dissertations

This study evaluates the impact of vitamin D plus calcium supplementation as a primary intervention for heart failure (HF) prevention and examines whether preexisting conditions that are precursors of HF modify this relationship in a large cohort of postmenopausal women. Analysis included 35,113 postmenopausal women (17,595 intervention, 17,518 control) aged 50 to 81 years enrolled in the randomized trial of vitamin D plus calcium (CaD) in the Women’s Health Initiative (WHI) study. The women in this analysis cohort were free of HF at the time of randomization and during the first year of the trial. The intervention consisted of 1,000 …

Partial Replacement Of Nacl Can Be Achieved With Potassium, Magnesium And Calcium Salts In Brown Bread, Karen Charlton, Naomi Levitt, Krisela Steyn, Elizabeth Macgregor, Nonnie Vorster

Karen E. Charlton

Objectives: To develop a reduced sodium bread in which salt (NaCl) is partially replaced with K, Mg, and Ca salts. Methods: Experimental bread was compared against standard brown bread, after a drop test (to assess whether bread quality deteriorates with abuse) and after usual baking practices for baking properties (volume, crust colour, crumb colour and cell structure), sensory properties and nutritional composition. Plant production feasibility was evaluated in an industrial plant. Breads produced there were subjected to sensory evaluation using triangulation tests in a panel of 122 consumers. Twenty-four samples of both standard and experimental bread were laboratory-analysed for Na, …

Glucose Stimulation Induces Dynamic Change Of Mitochondrial Morphology To Promote Insulin Secretion In The Insulinoma Cell Line Ins-1e., Bong Sook Jhun, Hakjoo Lee, Zheng-Gen Jin, Yisang Yoon

Center for Translational Medicine Faculty Papers

Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production which evokes Ca(2+) influx through plasma membrane depolarization, triggering insulin vesicle exocytosis. Therefore, GSIS reflects mitochondrial function and can be used for evaluating functional changes associated with morphological alterations of mitochondria. Using the insulin-secreting cell line INS-1E, we found that glucose stimulation induced rapid mitochondrial shortening and recovery. Inhibition of mitochondrial fission through expression of the dominant-negative mutant DLP1-K38A eliminated this dynamic mitochondrial shape change …

Calcium And Vitamin D For The Reproductive Female, Rachel A. Maassen

Rachel A Maassen

The importance of calcium as well as its interdependence upon vitamin D is well established. Vitamin D acts via the vitamin D receptor, which is found in 37 different human tissues. Because of its rather ubiquitous localization, vitamin D is the topic of a great deal of associative research. However, caution must be exercised in interpreting these initial studies until clear evidence for causality becomes available. The purpose of this article is to review some of the known vitamin D and calcium associations as well as the current guidelines for calcium and vitamin D supplementation.

Single-Cell Measurements Of Ige-Mediated Fcεri Signaling Using An Integrated Microfluidic Platform, Yanli Liu, Dipak Barua, Peng Liu, Bridget S. Wilson, Janet M. Oliver, William S. Hlavacek, Anup K. Singh

Chemical and Biochemical Engineering Faculty Research & Creative Works

Heterogeneity in responses of cells to a stimulus, such as a pathogen or allergen, can potentially play an important role in deciding the fate of the responding cell population and the overall systemic response. Measuring heterogeneous responses requires tools capable of interrogating individual cells. Cell signaling studies commonly do not have single-cell resolution because of the limitations of techniques used such as Westerns, ELISAs, mass spectrometry, and DNA microarrays. Microfluidics devices are increasingly being used to overcome these limitations. Here, we report on a microfluidic platform for cell signaling analysis that combines two orthogonal single-cell measurement technologies: on-chip flow cytometry …

Nanosecond Pulsed Electric Field Thresholds For Nanopore Formation In Neural Cells., Caleb C Roth, Gleb P Tolstykh, Jason A Payne, Marjorie A Kuipers, Gary L. Thompson Iii, Mauris N Desilva, Bennett L Ibey

Henry M. Rowan College of Engineering Departmental Research

The persistent influx of ions through nanopores created upon cellular exposure to nanosecond pulse electric fields (nsPEF) could be used to modulate neuronal function. One ion, calcium (Ca(2+)), is important to action potential firing and regulates many ion channels. However, uncontrolled hyper-excitability of neurons leads to Ca(2+) overload and neurodegeneration. Thus, to prevent unintended consequences of nsPEF-induced neural stimulation, knowledge of optimum exposure parameters is required. We determined the relationship between nsPEF exposure parameters (pulse width and amplitude) and nanopore formation in two cell types: rodent neuroblastoma (NG108) and mouse primary hippocampal neurons (PHN). We identified thresholds for nanoporation using …

Honokiol Blocks Store Operated Calcium Entry In Cho Cells Expressing The M3 Muscarinic Receptor: Honokiol And Muscarinic Signaling, Hsiu-Jen Wang, Alexis Martin, Po-Kuan Chao, Rhett A. Reichard, Adam L. Martin, Yue-Wern Huang, Ming-Huan Chan, Robert Aronstam

Biological Sciences Faculty Research & Creative Works

Background: Honokiol, a cell-permeable phenolic compound derived from the bark of magnolia trees and present in Asian herbal teas, has a unique array of pharmacological actions, including the inhibition of multiple autonomic responses. We determined the effects of honokiol on calcium signaling underlying transmission mediated by human M3 muscarinic receptors expressed in Chinese hamster ovary (CHO) cells. Receptor binding was determined in radiolabelled ligand binding assays; changes in intracellular calcium concentrations were determined using a fura-2 ratiometric imaging protocol; cytotoxicity was determined using a dye reduction assay.

Results: Honokiol had a potent (EC50 ≈ 5 μmol/l) inhibitory effect on store …

Impact Of High Calcium Intake From Calcium Carbonate Or Dairy On Cardiovascular Function, Coronary Artery Calcification And Coronary Artery Disease Burden In Ossabaw Miniature Swine, Alyssa K. Phillips

Open Access Theses

Recent secondary analyses have associated supplemental calcium use with increased risk for myocardial infarction and cardiovascular-related death in healthy, older adults. Subsequent concern over the safety of calcium supplements has spurred a calcium controversy, because calcium is a shortfall essential nutrient that is critical for bone health and a mainstay of osteoporosis prevention and treatment. The proposed mechanism by which calcium intake may detriment cardiovascular health is through the acceleration of coronary artery calcification (CAC), a clinical indicator of coronary artery disease (CAD) that has been associated with mortality risk. However, causal evidence to support this hypothesis is lacking. Determining …

Modulation Of Renin Secretion By Renal Cortical Interstitial Calcium, Douglas K. Atchison

Wayne State University Dissertations

Renin is secreted from the juxtaglomerular (JG) cells of the afferent arteriole of the kidney, and is the rate-limiting enzyme of the renin-angiotensin system. Renin is quantified in vivo as plasma renin activity (PRA). Acutely elevating plasma calcium decreases PRA, but the mechanisms by which this occurs is unknown. The overall goal of our study was to determine how elevated plasma calcium decreases PRA. The calcium-sensing receptor (CaSR) is a ubiquitously expressed receptor that translates changes in plasma calcium into changes in intracellular signaling. JG cells are basolaterally bordered by the renal cortical interstitium, and parathyroid hormone (PTH) positively regulates …

Early Hemodynamic And Biochemical Changes In Overloaded Swine Ventricle.Early Hemodynamic And Biochemical Changes In Overloaded Swine Ventricle, Sandro Gelsomino, Fabiana Lucà, Chiara Nediani, Sandra Zecchi Orlandini, Daniele Bani, Antonio S Rubino, Attilio Renzulli, Roberto Lorusso, Andrea Consolo, Antonino Lo Cascio, Jos Maessen, Gian Franco Gensini

The Texas Heart Institute Journal

The present study was undertaken to investigate, in an animal model, the relationship between sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity, phospholamban phosphorylation, acylphosphatase activity, and hemodynamic changes that occur in the early phase of pressure overload. In 54 study-group pigs, weighing 40±5 kg each, an aortic stenosis was created with a band of umbilical tape tied around the aorta; 18 sham-operated pigs formed our control group. Eight animals (6 study and 2 control) were randomly assigned to each experimental time (0.5, 3, 6, 12, 24, 48, 72, 96, and 168 hr). All indices of left ventricular function declined significantly, with a …

A Geospatial Assessment Of The Relationship Between Reef Flat Community Calcium Carbonate Production And Wave Energy, S M. Hamylton, A Pescud, J X. Leon, D Callaghan

Faculty of Science, Medicine and Health - Papers: part A

The ability of benthic communities inhabiting coral reefs to produce calcium carbonate underpins the development of reef platforms and associated sedimentary landforms, as well as the fixation of inorganic carbon and buffering of diurnal pH fluctuations in ocean surface waters. Quantification of the relationship between reef flat community calcium carbonate production and wave energy provides an empirical basis for understanding and managing this functionally important process. This study employs geospatial techniques across the reef platform at Lizard Island, Great Barrier Reef, to (1) map the distribution and estimate the total magnitude of reef community carbonate production and (2) empirically ascertain …

Association Of Iron Depletion With Menstruation And Dietary Intake Indices In Pubertal Girls: The Healthy Growth Study, George Moschonis, Dimitrios Papandreou, Christina Mavrogianni, Angeliki Giannopoulou, Louisa Damianidi, Pavlos Malindretos, Christos Lionis, George P. Chrousos, Yannis Manios

All Works

The aim of the present study was to investigate the associations of iron depletion (ID) with menstrual blood losses, lifestyle, and dietary habits, in pubertal girls. The study sample comprised 1222 girls aged 9-13 years old. Biochemical, anthropometrical, dietary, clinical, and physical activity data were collected. Out of 274 adolescent girls with menses, 33.5% were found to be iron depleted (defined as serum ferritin < 12 g/L) compared to 15.9% out of 948 girls without menses. Iron-depleted girls without menses were found to have lower consumption of poultry (P = 0.017) and higher consumption of fruits (P = 0.044) and fast food (P = 0.041) compared to their peers having normal iron status. Multivariate logistic regression analysis showed that girls with menses were 2.57 (95% CI: 1.37, 4.81) times more likely of being iron depleted compared to girls with no menses. Iron depletion was found to be associated with high calcium intake, high consumption of fast foods, and low consumption of poultry and fruits. Menses was the only factor that was found to significantly increase the likelihood of ID in these girls. More future research is probably needed in order to better understand the role of diet and menses in iron depletion. © 2013 George Moschonis et al.