Physiology Commons^™

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker

Theses & Dissertations

Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K⁺ currents. Another pathway that has profound effects on neuronal K⁺ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through …

Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter

Natalie G. Farny

Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice …

Cardioprotective Role Of The Cholinergic System, Mouhamed Dakroub

Electronic Thesis and Dissertation Repository

The process of aging is an irreversible continuum experienced by all individuals. A large number of physiological transformations occur to the cardiovascular system as one ages. These changes result in increased risk of developing cardiovascular diseases, many of which are frequently seen in geriatric populations. While the exact mechanisms of age-related cardiac dysfunction have not been established, abnormal cholinergic dysfunction has been implicated in the pathology of other age related diseases; therefore, we have hypothesized that age induced cholinergic dysfunction is detrimental to cardiac function and health. This study seeks to identify whether increased cholinergic signaling, either by transgenic overexpression …

Dexamethasone Regulates Gene Expression Induced By The Mechanosensitive P2x7 Receptor In Osteoblasts, Meena Na

Electronic Thesis and Dissertation Repository

Orthodontic tooth movement involves activation of osteoblasts and osteoclasts in response to mechanical forces. Extracellular nucleotides, released in response to mechanical stimuli, signal through P2 receptors in osteoblasts. P2X7 receptors are ATP-gated cation channels implicated in mechanotransduction in bone. Corticosteroids such as dexamethasone exhibit anti-inflammatory effects and their chronic use has been linked to serious side-effects such as osteoporosis. We investigated gene expression following P2X7 receptor activation with benzoylbenzoyl-ATP (P2X7 receptor agonist) in osteoblast precursor cells in the presence or absence of dexamethasone. We hypothesized that dexamethasone inhibits the ability of ATP to stimulate the expression of anabolic (bone forming) …

Chemical-Free Technique To Study The Ultrastructure Of Primary Cilium, Ashraf M. Mohieldin, Wissam A. Aboualaiwi, Min Gao, Surya M. Nauli

Pharmacy Faculty Articles and Research

A primary cilium is a hair-like structure with a width of approximately 200 nm. Over the past few decades, the main challenge in the study of the ultrastructure of cilia has been the high sensitivity of cilia to chemical fixation, which is required for many imaging techniques. In this report, we demonstrate a combined high-pressure freezing (HPF) and freeze-fracture transmission electron microscopy (FFTEM) technique to examine the ultrastructure of a cilium. Our objective is to develop an optimal high-resolution imaging approach that preserves cilia structures in their best natural form without alteration of cilia morphology by chemical fixation interference. Our …

Bdnf Contributes To Angiotensin Ii-Mediated Reductions In Peak Voltage-Gated K+ Current In Cultured Cath.A Cells., Bryan K. Becker, Han-Jun Wang, Changhai Tian, Irving H. Zucker

Journal Articles: Cellular & Integrative Physiology

Increased central angiotensin II (Ang II) levels contribute to sympathoexcitation in cardiovascular disease states such as chronic heart failure and hypertension. One mechanism by which Ang II increases neuronal excitability is through a decrease in voltage-gated, rapidly inactivating K(+) current (IA); however, little is known about how Ang II signaling results in reduced IA. Brain-derived neurotrophic factor (BDNF) has also been demonstrated to decrease IA and has signaling components common to Ang II. Therefore, we hypothesized that Ang II-mediated suppression of voltage-gated K(+) currents is due, in part, to BDNF signaling. Differentiated CATH.a, catecholaminergic cell line treated with BDNF for …

Mcnamara 201412 Nih Scap Innocentive Challenge Solution - T-Bow Rainbow T-Cells And Tumor Cells Spatial Multiplexing Gene Expression Reporter System – Plus Supplement Plus Posters - 20151027 - Please Download "75" Instead, George Mcnamara

George McNamara

McNamara 201412 NIH SCAP InnoCentive Challenge Solution - T-Bow Rainbow T-cells and Tumor Cells Spatial Multiplexing Gene Expression Reporter System – plus supplement plus posters - 20151027.

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Please download the current 20151027 (October 27, 2015) Tattletales and T-Bow update from

http://works.bepress.com/gmcnamara/75/

The bepress web site is not letting me replace the old pdf here at "65" with the additional 10 pages update.

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The download is my/Cooper lab solution (submission) to the 2014 NIH Single Cell Analysis Program (SCAP) InnoCentive Challenge, "Follow That Cell". I submitted the Solution on 20141215Mon (with 20 minutes to spare). The Challenge web page …

P53: "The Wall Watcher", Nektarios Barabutis, John D. Catravas

Bioelectrics Publications

No abstract provided.

Control Of Stem Cell Self-Renewal And Differentiation By The Heterochronic Genes And The Cellular Asymmetry Machinery In Caenorhabditis Elegans, Omid F. Harandi, Victor Ambros

Victor R. Ambros

Transitions between asymmetric (self-renewing) and symmetric (proliferative) cell divisions are robustly regulated in the context of normal development and tissue homeostasis. To genetically assess the regulation of these transitions, we used the postembryonic epithelial stem (seam) cell lineages of Caenorhabditis elegans. In these lineages, the timing of these transitions is regulated by the evolutionarily conserved heterochronic pathway, whereas cell division asymmetry is conferred by a pathway consisting of Wnt (Wingless) pathway components, including posterior pharynx defect (POP-1)/TCF, APC related/adenomatosis polyposis coli (APR-1)/APC, and LIT-1/NLK (loss of intestine/Nemo-like kinase). Here we explore the genetic regulatory mechanisms underlying stage-specific transitions between self-renewing …

Mir-14 Regulates Autophagy During Developmental Cell Death By Targeting Ip3-Kinase 2, Charles Nelson, Victor Ambros, Eric Baehrecke

Victor R. Ambros

Macroautophagy (autophagy) is a lysosome-dependent degradation process that has been implicated in age-associated diseases. Autophagy is involved in both cell survival and cell death, but little is known about the mechanisms that distinguish its use during these distinct cell fates. Here, we identify the microRNA miR-14 as being both necessary and sufficient for autophagy during developmentally regulated cell death in Drosophila. Loss of miR-14 prevented induction of autophagy during salivary gland cell death, but had no effect on starvation-induced autophagy in the fat body. Moreover, misexpression of miR-14 was sufficient to prematurely induce autophagy in salivary glands, but not in …

Relevance Of The Carotid Body Chemoreflex In The Progression Of Heart Failure., David C. Andrade, Claudia Lucero, Camilo Toledo, Carlos Madrid, Noah J. Marcus, Harold D. Schultz, Rodrigo Del Rio

Journal Articles: Cellular & Integrative Physiology

Chronic heart failure (CHF) is a global health problem affecting millions of people. Autonomic dysfunction and disordered breathing patterns are commonly observed in patients with CHF, and both are strongly related to poor prognosis and high mortality risk. Tonic activation of carotid body (CB) chemoreceptors contributes to sympathoexcitation and disordered breathing patterns in experimental models of CHF. Recent studies show that ablation of the CB chemoreceptors improves autonomic function and breathing control in CHF and improves survival. These exciting findings indicate that alterations in CB function are critical to the progression of CHF. Therefore, better understanding of the physiology of …

Elongation Factor-P At The Crossroads Of The Host-Endosymbiont Interface, Andrei Rajkovic, Anne Witzky, William Navarre, Andrew J. Darwin, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is an ancient bacterial translational factor that aids the ribosome in polymerizing oligo-prolines. EF-P structurally resembles tRNA and binds in-between the exit and peptidyl sites of the ribosome to accelerate the intrinsically slow reaction of peptidyl-prolyl bond formation. Recent studies have identified in separate organisms, two evolutionarily convergent EF-P post-translational modification systems (EPMS), split predominantly between gammaproteobacteria, and betaproteobacteria. In both cases EF-P receives a post-translational modification, critical for its function, on a highly conserved residue that protrudes into the peptidyl-transfer center of the ribosome. EPMSs are comprised of a gene(s) that synthesizes the precursor molecule …

Multi-Stress Proteomics: The Global Protein Response To Multiple Environmental Stressors In The Porcelain Crab Petrolisthes Cinctipes, Michael A. Garland

Master's Theses

Global climate change is increasing the number of hot days along the California coast as well as increasing the incidence of off-shore upwelling events that lower the pH of intertidal seawater; thus, intertidal organisms are experiencing an increase in more than one stress simultaneously. This study seeks to characterize the global protein response of the eurythermal porcelain crab Petrolisthes cinctipes to changes in thermal, pH, and tidal regime treatments, either combined or individually. The first experiment examined temperature stress alone and sought to determine the effect of chronic temperature acclimation on the acute heat shock response. We compared the proteomic …

Engineered Cx26 Variant Established Functional Heterotypic Cx26/Cx43 And Cx26/Cx40 Gap Junction Channels, Levent Berk Karademir

Electronic Thesis and Dissertation Repository

Two hexameric connexin hemichannels dock together to from a whole gap junction (GJ) channel. The mechanisms of docking specificity in forming homotypic and heterotypic GJ channels are not fully clear. To reveal the key differences between Cx26 and Cx43 (or Cx40) in their docking residues, we aligned and analyzed ten well studied connexin sequences. Five of them are docking compatible with Cx26 and the rest (including Cx43 and Cx40) are not. According to Cx26 crystal structure at the docking interface, we identified two putative docking residues on the second extracellular domain (E2) that are well conserved within docking compatible connexins, …

Molecular Mechanisms Underlying The Contralateral Repeated Bout Effect (Crbe) In Human Skeletal Muscle, Ling Xin

Doctoral Dissertations

Eccentric (muscle lengthening) exercise induces temporary muscle damage that can lead to long-term muscle adaptation, a process known as the repeated bout effect where subsequent exercise results in less damage. The existence of a contralateral repeated bout effect (CRBE) has been controversial. The primary goals of this study were to: 1) validate the existence of the CRBE; and 2) define the underlying molecular mechanisms. Thirty-six young men performed 100 maximal eccentric actions of the knee extensors using one leg (bout 1) and repeated the exercise with the contralateral leg five weeks later (bout 2). Vastus lateralis muscle biopsies were …

Role Of Rgs2 In Cellular Stress, Chang-Hui Wang

Electronic Thesis and Dissertation Repository

Stresses from the external environment can disrupt cellular processes and result in damaging effects, such as the misfolding of proteins, which have been linked to several diseases. Regulator of G protein signalling 2 (RGS2) is upregulated by several forms of stress and can inhibit protein synthesis, an established response to stress typically achieved via the phosphorylation of the initiation factor, eIF2, to conserve energy and resources. Under reduced translation, some factors are selectively expressed via alternative translation mechanisms and these factors consequently may promote apoptosis. The molecular mechanisms mediating such opposing responses to stress are not well understood. Here, we …

Fibulin-3 Promotes Triple Negative Breast Cancer Cell Invasion, Michelle M. Noonan

Electronic Thesis and Dissertation Repository

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and metastasis is a leading cause of mortality in these patients. Fibulin-3, a secreted extracellular matrix protein, has a pro-invasive role in other cancers. However, a role for fibulin-3 in TNBC invasion is unknown. We have previously shown that KISS1R signaling promotes TNBC cell invasion through EGFR and MMP-9 activity, via β-arrestin2. Thus, we hypothesized that KISS1R signaling promotes TNBC cell invasion via fibulin-3. Our clinical data suggests that plasma fibulin-3 levels are elevated in metastatic TNBC patients. Additionally, we found that invasive breast cancer cells have increased …

Stability And Activity Of Naturally Occurring Rgs2 Variants, Patrick Stockwell

Electronic Thesis and Dissertation Repository

Regulator of G protein signaling protein 2 (RGS2) attenuates G Protein-Coupled Receptor (GPCR) signaling by promoting the hydrolysis of GTP in the activated Gα subunit to GDP, thereby governing many physiological and pathophysiological signals. However, how RGS2 itself is regulated remains to be elucidated. In this study, our principal goal was to discover the molecular mechanisms controlling RGS2 degradation and if altered degradation affects Gα signaling. RGS2 has four initiation sites (at residues 1, 5, 16, and 33), resulting in the existence of four distinct N-terminal initiation site variants. Additionally, there are naturally occurring mutations in this region at residues …

Gating Mechanisms Of The Canonical Trp Channel Isoform Trpc4, Dhananjay P. Thakur

Dissertations & Theses (Open Access)

Non-selective cation channels formed by Transient Receptor Potential Canonical (TRPC) proteins play important roles in regulatory and pathophysiological processes. These channels are known to be activated downstream from phospholipase C (PLC) signaling. However, the mechanism by which the PLC pathway activates TRPC4/C5 remains unclear. Uniquely, TRPC4 is maximally activated only when two separate G protein pathways, G_q/11 and G_i/o, are co-stimulated, making it a coincidence detector of G_q/11- and G_i/o -coupled receptor activation. Using HEK293 cells co-expressing mouse TRPC4β and selected G protein-coupled receptors, I observed that coincident stimulation of G_i/o proteins and …

Hippocalcin Response To Calcium: Do Conserved Tryptophans – W30 Or W103 – Matter?, Sunkesula K. Sagar

Graduate School of Biomedical Sciences Theses and Dissertations

Changes in intracellular calcium levels play a very important role in cell signaling, in turn, affecting neuronal functions such as memory, learning and cell death. A class of proteins called Neuronal Calcium Sensor (NCS) proteins serves to modulate the functioning of the neuronal cells in response to changes in calcium levels, and prevent neuronal apoptosis. Structurally, all NCS proteins have 4 calcium-binding EF hand motifs, although EF1 does not bind to calcium in many members. All NCS proteins have an acyl modification at the N- terminus – where a myristoyl group is added post-translationally. Hippocalcin (HPCA) is an NCS protein, …

Monitoring The Progression Of Spontaneous Articular Cartilage Healing With Infrared Spectroscopy, Megan P. O'Brien, Madhuri Penmatsa, Uday Palukuru, Paul West, Xu Yang, Mathias P. G. Bostrom, Theresa Freeman, Nancy Pleshko

Publications and Research

Objective. Evaluation of early compositional changes in healing articular cartilage is critical for understanding tissue repair and for therapeutic decision-making. Fourier transform infrared imaging spectroscopy (FT-IRIS) can be used to assess the molecular composition of harvested repair tissue. Furthermore, use of an infrared fiber-optic probe (IFOP) has the potential for translation to a clinical setting to provide molecular information in situ. In the current study, we determined the feasibility of IFOP assessment of cartilage repair tissue in a rabbit model, and assessed correlations with gold-standard histology.

Design. Bilateral osteochondral defects were generated in mature white New Zealand rabbits, and …

Editorial: Carotid Body: A New Target For Rescuing Neural Control Of Cardiorespiratory Balance In Disease., Rodrigo Del Rio, Rodrigo Iturriaga, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

No abstract provided.

Cyclic Rhamnosylated Elongation Factor P Establishes Antibiotic Resistance In Pseudomonas Aeruginosa, Andrei Rajkovic, Sarah Erickson, Anne Witzky, Owen E. Branson, Jin Seo, Philip R. Gafken, Michael A. Frietas, Julian P. Whitelegge, Kym F. Faull, William Wiley Navarre, Andrew J. Darwin, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is a ubiquitous bacterial protein that is required for the synthesis of poly-proline motifs during translation. In Escherichia coli and Salmonella enterica, the posttranslational β-lysylation of Lys34 by the PoxA protein is critical for EF-P activity. PoxA is absent from many bacterial species such as Pseudomonas aeruginosa, prompting a search for alternative EF-P posttranslation modification pathways. Structural analyses of P. aeruginosa EF-P revealed the attachment of a single cyclic rhamnose moiety to an Arg residue at a position equivalent to that at which β-Lys is attached to E. coli EF-P. Analysis of the genomes …

Orexin Receptor Activation Generates Gamma Band Input To Cholinergic And Serotonergic Arousal System Neurons And Drives An Intrinsic Ca(2+)-Dependent Resonance In Ldt And Ppt Cholinergic Neurons, Masaru Ishibashi, Iryna Gumenchuk, Bryan Kang, Catherine Steger, Elizabeth Lynn, Nancy Molina, Leonard M. Eisenberg, Christopher S. Leonard

NYMC Faculty Publications

A hallmark of the waking state is a shift in EEG power to higher frequencies with epochs of synchronized intracortical gamma activity (30-60 Hz) - a process associated with high-level cognitive functions. The ascending arousal system, including cholinergic laterodorsal (LDT) and pedunculopontine (PPT) tegmental neurons and serotonergic dorsal raphe (DR) neurons, promotes this state. Recently, this system has been proposed as a gamma wave generator, in part, because some neurons produce high-threshold, Ca(2+)-dependent oscillations at gamma frequencies. However, it is not known whether arousal-related inputs to these neurons generate such oscillations, or whether such oscillations are ever transmitted to neuronal …

Drug-Resistant Hiv-1 Protease Regains Functional Dynamics Through Cleavage Site Coevolution, Nevra Ozer, Aysegul Ozen, Celia Schiffer, Turkan Haliloglu

Celia A. Schiffer

Drug resistance is caused by mutations that change the balance of recognition favoring substrate cleavage over inhibitor binding. Here, a structural dynamics perspective of the regained wild-type functioning in mutant HIV-1 proteases with coevolution of the natural substrates is provided. The collective dynamics of mutant structures of the protease bound to p1-p6 and NC-p1 substrates are assessed using the Anisotropic Network Model (ANM). The drug-induced protease mutations perturb the mechanistically crucial hinge axes that involve key sites for substrate binding and dimerization and mainly coordinate the intrinsic dynamics. Yet with substrate coevolution, while the wild-type dynamic behavior is restored in …

Discovering The Sequence Specificity Of Human Dyrk2 And Dyrk4, Julie Klaric

University Scholar Projects

Protein phosphorylation is a post-translational modification (PTM) that is ubiquitous in regulating cellular processes. It is the most common PTM used in signal translation. Protein kinases are the class of enzymes that catalyze the transfer of a phosphate group from ATP to a specific amino acid on a substrate protein. In eukaryotes, kinases generally add a phosphate to serine, threonine, or tyrosine residues. Short linear patterns in the amino acid sequence of the substrate protein help guide the protein kinase to the correct residue to be phosphorylated. However, these patterns, or “motifs,” as well as the complete list of substrates …

Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr.

Honors Scholar Theses

Repeated concussive traumatic brain injury (rcTBI) is the most prominent form of head injury affecting the brain, with an estimated 1.7 million Americans affected each year (Kuhn 2012). Neurologists have been concerned about the danger of repeated head impacts since the 1920’s, but researchers have only begun to understand the long-term effects of rcTBI (McKee 2009). Although symptoms can be as mild as dizziness, current research suggests that multiple concussions can lead to a progressive degenerative brain disease known as chronic traumatic encephalopathy (CTE) (Luo 2008, McKee 2009, Kane 2013). Research on the brain is just beginning to scratch the …

Functional Significance Of Gill Claudin Proteins In Rainbow Trout (Oncorhynchus Mykiss) Osmoregulation, Joanna Katarzyna Bujak

Graduate Theses and Dissertations

Claudin proteins, a key element of tight junction complexes, are known to control paracellular permeability. In euryhaline fish, changes in claudin abundance and localization are critical during salinity acclimation. In seawater, a leaky paracellular pathway that facilitates sodium extrusion is hypothesized to be controlled by claudin proteins. The aim of this study was to evaluate the role of Claudin-10c, -10d -10e and Claudin-30 in gill function in freshwater (FW) and seawater (SW) rainbow trout (Oncorhynchus mykiss). I examined mRNA and protein abundance along with cellular localization. A tissue distribution survey showed that all of the claudins studied were predominantly expressed …

The Development Of Skeletal Muscle In Young Horses: An Ultrasonography And Satellite Cell Approach, Emma K. Lavigne

Honors Scholar Theses

Muscle growth in young horses is characterized by an increase in muscle cross-sectional area, which can be accomplished through the activation and differentiation of satellite cells. Satellite cells can be stimulated or inhibited in response to different cytokines and growth factors and are key mediators of muscle hypertrophy and regeneration. The aim of this study was to investigate the growth of the longissimus dorsi (LD) muscle in horses under 5 years of age and to obtain preliminary data on satellite cell behavior in foals. The area, width, height, and subcutaneous fat were measured using ultrasonography at 6-month increments over the …

Differential Activation Of Microglia In An In Vitro Model Of Intracerebral Hemorrhage, Bhakti Patel

Honors Capstone Projects - All

An in vitro model of intracerebral hemorrhage was established to examine the protective versus cytotoxic roles of microglia in the context of mild versus severe injury. Co-cultures of microglia, astrocytes, and granule neurons were prepared from the cerebellar cortex of neonatal rats, and grown in standard medium containing fetal bovine serum or, in some cases, a serum-free chemically defined medium. To mimic hemorrhagic stroke, co-cultures grown for 7-8 days in vitro were challenged with two different concentrations of the toxic blood product hemin, corresponding to a mild versus a severe brain bleed. Immunocyto-chemical, real-time RT-PCR, iron deposition, and cell survival …