Life Sciences Commons^™

C-Met Initiates Epithelial Scattering Through Transient Calcium Influxes And Nfat-Dependent Gene Transcription, Peter R. Langford

Theses and Dissertations

Hepatocyte growth factor (HGF) signaling drives epithelial cells to scatter by breaking cell-cell adhesions and migrating as solitary cells, a process that parallels epithelial-mesenchymal transition. HGF binds and activates the c-Met receptor tyrosine kinase, but downstream signaling required for scattering remains poorly defined. This study addresses this shortcoming in a number of ways.A high-throughput in vitro drug screen was employed to identify proteins necessary in this HGF-induced signaling. Cells were tested for reactivity to HGF stimulation in a Boyden chamber assay. This tactic yielded several small molecules that block HGF-induced scattering, including a calcium channel blocker. Patch clamping was used …

Analysis Of The Mechanism By Which Calcium Negatively Regulates The Tyrosine Phosphorylation Cascade Associated With Sperm Capacitation, Mark Baker, Louise Hethrington, Heath Ecroyd, Shaun Roman, Robert Aitken

Heath Ecroyd

The capacitation of mammalian spermatozoa involves the activation of a cAMP-mediated signal transduction pathway that drives tyrosine phosphorylation via mechanisms that are unique to this cell type. Controversy surrounds the impact of extracellular calcium on this process, with positive and negative effects being recorded in independent publications. We clearly demonstrate that the presence of calcium in the external medium decreases tyrosine phosphorylation in both human and mouse spermatozoa. Under these conditions, a rise in intracellular pH was recorded, however, this event was not responsible for the observed changes in phosphotyrosine expression. Rather, the impact of calcium on tyrosine phosphorylation in …

The Development Of Signal Transduction Pathways During Epididymal Maturation Is Calcium Dependent, Heath W. Ecroyd, Kelly Asquith, Russell C. Jones, Robert J. Aitken

Heath Ecroyd

Capacitation has been correlated with the activation of a cAMP-PKA-dependent signaling pathway leading to protein tyrosine phosphorylation. The ability to exhibit this response to cAMP matures during epididymal maturation in concert with the ability of the sperrnatozoa to capacitate. In this study, we have addressed the mechanisms by which spermatozoa gain the potential to activate this signaling pathway during epididymal maturation. In a modified Tyrode's medium containing 1.7 mM calcium, caput spermatozoa had significantly higher [Ca2+](i) than caudal cells and could not tyrosine phosphorylate in response to cAMP. However, in calcium-depleted medium both caput and caudal cells could exhibit a …

The Relationship Between Vitamin D And Calcium/Dairy Intake And Obesity In Children, Jason Barry

Nutrition Theses

Objective: The aim of this study is to examine the relationship between vitamin D and calcium intake and obesity in a population of young adolescents who participated in a Vitamin D and Sunlight Exposure study in Pittsburgh, PA.

Participants: 252 healthy 6 to 14.9 year old young adolescents (54% male, 69% African American) were recruited between June 2006 and December 2009.

Main outcome measures: Weight status, BMI, vitamin D intake, calcium intake, vitamin D and calcium rich food intake.

Results: A significant difference by race was observed with 30.1% of African Americans and 8.5% of Caucasians being obese (P<0.01). No difference was found by gender. Median (25%, 75%) vitamin D intake in the total population was 254.9 IU (146.8, 407.3) which is below the level recommended by the Institute of Medicine. Median calcium intake in the total population was 1193.6 mg (752.8, 1161.1) which met recommended guidelines. Median vitamin D intake differed by weight status (normal, overweight, obese) in the total population (259.5 IU, 325.2 IU and 181.9 IU, respectively; P=0.015). A similar pattern was observed for calcium (1193.4 mg, 1416.3 mg and 911.6 mg, respectively; P=0.016). No correlation was found between vitamin D or calcium intake and BMI in the total population or by race and gender.

Conclusion: …

Fertilization Characteristics Of Spermatozoa Collected From Bulls Grazing Tall Fescue Pastures, Jessica Pegan Harris

Masters Theses

Consumption of toxic endophyte-infected (E+) tall fescue pastures is known to have a negative impact on bull reproductive performance. Since decreased cleavage rates of embryos fertilized with spermatozoa from bulls grazing E+ tall fescue pastures have been observed in several studies using differing sets of bulls, technicians, pastures, and other methods of inducing tall fescue toxicosis (ergotamine tartrate), it is hypothesized that spermatozoa function from bulls grazing E+ is impaired in ways undetectable by gross semen examination.

During a three-month grazing study, 6 Angus bulls were utilized to determine the effects of grazing E+ tall fescue pastures on growth performance …

Store-Operated Ca(2+) Entry (Soce) Contributes To Normal Skeletal Muscle Contractility In Young But Not In Aged Skeletal Muscle, Angela M. Thornton, Xiaoli Zhao, Noah Weisleder, Leticia S. Brotto, Sylvain Bougoin, Thomas M. Nosek, Michael B. Reid, Brian Hardin, Zui Pan, Jianjie Ma, Jerome Parness, Marco Brotto

Physiology Faculty Publications

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular …

The Csc Is Required For Complete Radial Spoke Assembly And Wild-Type Ciliary Motility, Erin E. Dymek, Thomas Heuser, Daniela Nicastro, Elizabeth F. Smith

Dartmouth Scholarship

The ubiquitous calcium binding protein, calmodulin (CaM), plays a major role in regulating the motility of all eukaryotic cilia and flagella. We previously identified a CaM and Spoke associated Complex (CSC) and provided evidence that this complex mediates regulatory signals between the radial spokes and dynein arms. We have now used an artificial microRNA (amiRNA) approach to reduce expression of two CSC subunits in Chlamydomonas. For all amiRNA mutants, the entire CSC is lacking or severely reduced in flagella. Structural studies of mutant axonemes revealed that assembly of radial spoke 2 is defective. Furthermore, analysis of both flagellar beating and …

Increased Mitochondrial Calcium Sensitivity And Abnormal Expression Of Innate Immunity Genes Precede Dopaminergic Defects In Pink1-Deficient Mice, Ravi S. Akundi, Zhenyu Huang, Joshua Eason, Jignesh D. Pandya, Lianteng Zhi, Wayne A. Cass, Patrick G. Sullivan, Hansruedi Büeler

Neuroscience Faculty Publications

BACKGROUND: PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²⁺ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice.

METHODS AND FINDINGS: Purified brain mitochondria of ^Pink1⁻/⁻ mice showed impaired Ca²⁺ storage capacity, resulting in increased Ca²⁺ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. …

Altered Calcium Handling In Cerebellar Purkinje Neurons With The Malignant Hyperthermia Mutation, Ryr1-Y522s/+, George C. Talbott

Electronic Theses and Dissertations

To investigate the etiology of malignant hyperthermia and central core disease, mouse models have recently been generated and characterized (Chelu et al., 2006). These RyRY522S/+ knock-in mutant mice provide an excellent tool to investigate calcium dysregulation, its pathological consequences, and potential therapeutic approaches. Skeletal muscle harboring this mutation exhibits calcium leak from internal stores and an increased sensitivity to activation by caffeine, voltage, and temperature (Durham et al., 2008). Although alterations in RyR1 channel function and resultant changes in cellular function have been characterized in skeletal muscle, the effects of MH mutations in RyR1 on central nervous system function have …

An Apoptosis Targeted Stimulus With Nanosecond Pulsed Electric Fields (Nspefs) In E4 Squamous Cell Carcinoma, Wei Ren, Stephen J. Beebe

Bioelectrics Publications

Stimuli directed towards activation of apoptosis mechanisms are an attractive approach to eliminate evasion of apoptosis, a ubiquitous cancer hallmark. In these in vitro studies, kinetics and electric field thresholds for several apoptosis characteristics are defined in E4 squamous carcinoma cells (SCC) exposed to ten 300 ns pulses with increasing electric fields. Cell death was [95% at the highest electric field and coincident with phosphatidylserine externalization, caspase and calpain activation in the presence and absence of cytochrome c release, decreases in Bid and mitochondria membrane potential (Δψm) without apparent changes reactive oxygen species levels or in Bcl2 and Bclxl levels. …

Calcium Regulation And Transmitter Release At Drosophila Larval Neuromuscular Junction, Tao He

Legacy Theses & Dissertations (2009 - 2024)

Calcium ions act as the most versatile 2nd messenger and are involved in an incredibly broad spectrum of biological processes. Proper cellular Ca2+ homeostasis is paramount in maintaining normal cell growth, functions, survival and programmed death. Hence, understanding Ca2+ regulation has been a goal of and a hot topic in cutting-edge biological research for decades. Recently, the advent of a new generation of Ca2+ indicators has made a major contribution to advances in understanding Ca2+ regulation (Grynkiewicz et al., 1985). Likewise, the application of Drosophila melanogaster as an animal model has provided tantalizing clues and fueled the progress of research …

An Evaluation Of The Nutritional Quality Evaluation Of Three Cultivars Of Syzygium Samarangense Under Malaysian Conditions, Amru Bin Nasrulhaq Boyce

Amru Bin Nasrulhaq Boyce

A study was carried out to selected physiological and biochemical characteristics of Syzygium samarangense for their physiological and biochemical characteristics at Functional Food Laboratory, University of Malaya, Kuala Lumpur. Various physiological and biochemical parameters were monitored during two seasons of fruit growth between October, 2009 to August, 2010 with the 'Giant green', 'Masam manis pink' and 'Jambu madu red' cultivars of S. samarangense. Ripened fruits of the different cultivars were collected from the experimental field of Banting, Selangor and analyzed for selected physiological parameters namely chlorophyll fluorescence, quantum yield, fruit weight, total yield, number of seed per fruit, seed weight …