Medicine and Health Sciences Commons^™

Roles Of Pgc-1Α/Ppars Pathway In Regulating Insulin Sensitivity In Mouse Skeletal Muscle Cells Under Prolonged Hypoxia, Yunyan Zhang

Electronic Thesis and Dissertation Repository

Using the C₂C₁₂ mouse myoblast cell line, I investigated how prolonged hypoxia affected components of the insulin signalling and FAO/PGC-1α/PPARs pathways, as they might impact insulin sensitivity in skeletal muscle cells.

Hypoxia resulted in lower p-Akt (Thr 308) and higher total cellular GLUT4 protein levels after 7 days of differentiation. This coincided with higher triglyceride content and alterations of the FAO/PGC-1α/PPARs components, both of which could contribute to the changes observed in the components of the insulin signalling pathway. Specifically, cells differentiating in 1% O₂ had lower SIRT1, PPAR- α, FATP4 and MCAD mRNA; accompanied by …

Gender Does Not Influence The Relationship Between Posterior Cruciate Ligament Design And Patient-Reported Outcomes In Patients Receiving Primary Unilateral Total Knee Arthroplasty, Ryan Milan

Electronic Thesis and Dissertation Repository

The effect of the interaction between gender and posterior cruciate ligament (PCL) prosthesis design on patient-reported outcomes is an understudied area of research. We evaluated 1613 patients, from the Ontario Joint Replacement Registry (2001-2006), who underwent primary total knee replacement. This study investigated the impact of the gender-PCL design interaction on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) change scores and patient satisfaction, by performing linear regression analysis, using full-adjusted models that also included the gender-PCL prosthesis design interaction variable. PCL prosthesis design did not affect WOMAC change scores or satisfaction (p>0.05). Moreover, Gender did not influence either …

Septohippocampal Gabaergic Neurons Mediate The Altered Behaviors Induced By N-Methyl-D-Aspartate Receptor Antagonists., Jingyi Ma, Siew Kian Tai, L Stan Leung

Physiology and Pharmacology Publications

We hypothesize that selective lesion of the septohippocampal GABAergic neurons suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine or MK-801. In addition, we hypothesize that septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm that coexists with an atropine-sensitive theta rhythm in the hippocampus. Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The theta rhythm during walking, or the immobility-associated theta induced by pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking theta was, however, more disrupted by atropine sulfate in ore-SAP than …

Neurophysiological Impact And Modeling-Independent Elucidation Of Inactivation Pathways In A-Type K+ Channels, J.D. Fineberg, David Ritter, Manuel Covarrubias

Department of Molecular Physiology and Biophysics Faculty Papers

Poster presented at Society for Neuroscience

Abstract:

A-type voltage-gated K⁺ channels auto-regulate their function by undergoing fast inactivation. Independent of molecular mechanisms, this inactivation can proceed after channel opening (open-state inactivation, OSI) or from a closed state prior to opening (closed-state inactivation, CSI). We hypothesize that the specific neurophysiological roles of A-type Kv channels depend on whether they undergo OSI, CSI or both (CSI+OSI). To explore these possibilities, we introduced Markov kinetic schemes of the A-type Kv4 conductance into a computational model of the hippocamcal CA1 neuron assuming either CSI or CSI+OSI and compared the properties of the somatic …

Latexin Is Down-Regulated In Hematopoietic Malignancies And Restoration Of Expression Inhibits Lymphoma Growth, Yi Liu, Dianna Howard, Kyle Rector, Carol Swiderski, Jason Brandon, Lawrence Schook, Jayesh Mehta, J. Scott Bryson, Subbarao Bondada, Ying Liang

Internal Medicine Faculty Publications

Latexin is a negative regulator of hematopoietic stem cell number in mice. Its dysregulated expression in other tumors led us to hypothesize that latexin may have tumor suppressor properties in hematological malignancies. We found that latexin was down-regulated in a variety of leukemia and lymphoma cell lines as well as in CD34+ cells from the blood and marrow of patients with these malignancies. 5-aza-2'-deoxycytodine treatment and bisulfite sequencing revealed hypermethylation of latexin promoter in tumor cells. Retrovirus-mediated latexin overexpression in A20 mouse lymphoma cells inhibited their in vitro growth by 16 fold and in vivo tumor volume by 2 fold. …

Phthalate Exposure Changes The Metabolic Profile Of Cardiac Muscle Cells, Nikki G. Posnack, Luther M. Swift, Matthew W. Kay, Norman H. Lee, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background: Phthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown.

Objectives: We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardiomyocytes because alterations in metabolic processes can lead to cell dysfunction.

Methods: Neonatal rat cardiomyocytes were treated with DEHP at a concentration and duration comparable to clinical exposure (50–100 μg/mL, 72 hr). We assessed the effect of DEHP on gene expression using microarray analysis. Physiological responses …

Increased Susceptibility To Metabolic Syndrome In Adult Offspring Of Angiotensin Type 1 Receptor Autoantibody-Positive Rats., Suli Zhang, Xi Zhang, Lihong Yang, Zi Yan, Li Yan, Jue Tian, Xiaoyu Li, Li Song, Li Wang, Xiaoli Yang, Ronghua Zheng, Wayne Bond Lau, Xinliang Ma, Huirong Liu

Department of Emergency Medicine Faculty Papers

Abstract Aims: Abnormal fetal and early postnatal growth is closely associated with adult-onset metabolic syndrome (MetS). However, the underlying etiological factors remain complex. The presence of the autoantibody against the angiotensin II type 1 receptor (AT1-Ab), a known risk factor for pre-eclampsia, may create a suboptimal intrauterine fetal environment. The current study investigated whether middle-aged offspring of AT1-Ab-positive mothers were prone to metabolic disorder development. Results: The AT1-Abs was detected in placental trophoblastic cells, capillary endothelium, and milk of pregnant rats actively immunized with the second extracellular loop of the AT1 receptor. AT1-Abs in newborn rats induced vasoconstriction, increased intracellular-free …

Regulated Proteolysis Controls Mucoid Conversion In Pseudomonas Aeruginosa, Dongru Qiu, Vonya Eisinger, Donald Rowen, Hongwei Yu

Hongwei Yu

Overproduction of the exopolysaccharide alginate causes mucoid conversion in Pseudomonas aeruginosa and is a poor prognosticator in cystic fibrosis. The ECF σ factor AlgU and its cognate anti-σ factor MucA are two principal regulators of alginate production. Here, we report the identification of three positive regulators of alginate biosynthesis: PA4033 (designated mucE), PA3649 (designated mucP), and algW. MucE, a small protein (9.5 kDa), was identified as part of a global mariner transposon screen for new regulators of alginate production. A transposon located in its promoter caused the overexpression of MucE and mucoid conversion in P. aeruginosa strains PAO1 and PA14. …

Antioxidant Rescue Of Nf1/Ras-Induced Myelin And Vasculature Dysfunction, Debra A. Mayes, Tilat A. Rizvi, Shyra J. Miller, Rachel Oberst, Anat Stemmer-Rachamimov, Nancy Ratner

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.

Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Molecular Identities Of Mitochondrial Ca2+ Influx Mechanism: Updated Passwords For Accessing Mitochondrial Ca2+-Linked Health And Disease., Jin O-Uchi, Shi Pan, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

No abstract provided.

Resting-State Connectivity Identifies Distinct Functional Networks In Macaque Cingulate Cortex., R Matthew Hutchison, Thilo Womelsdorf, Joseph S Gati, L Stan Leung, Ravi S Menon, Stefan Everling

Physiology and Pharmacology Publications

Subregions of the cingulate cortex represent prominent intersections in the structural networks of the primate brain. The relevance of the cingulate to the structure and dynamics of large-scale networks ultimately requires a link to functional connectivity. Here, we map fine-grained functional connectivity across the complete extent of the macaque (Macaca fascicularis) cingulate cortex and delineate subdivisions pertaining to distinct identifiable networks. In particular, we identified 4 primary networks representing the functional spectrum of the cingulate: somatomotor, attention-orienting, executive, and limbic. The cingulate nodes of these networks originated from separable subfields along the rostral-to-caudal axis and were characterized by positive and …

Methodological Challenges And Clinical Applications Of Hair Cortisol Analysis, Evan W. Russell

Electronic Thesis and Dissertation Repository

This thesis examines methodological and clinical aspects of hair cortisol analysis. The methodological study examines the role of sweat as a contributor to hair cortisol concentrations. Hair cortisol analysis is an effective measure of chronic stress. Cortisol is assumed to enter the hair via blood, sebum, and sweat, however the extent to which sweat contributes to hair cortisol content was unknown. This study concluded that human sweat contains cortisol that likely contributes to hair cortisol content. Subjects with prolonged sweating at the time of hair collection may have increased hair cortisol concentrations that cannot be decreased with conventional laboratory washing …

Synaptic And Intrinsic Activation Of Gabaergic Neurons In The Cardiorespiratory Brainstem Network, Julie G. Frank, David Mendelowitz

Pharmacology and Physiology Faculty Publications

GABAergic pathways in the brainstem play an essential role in respiratory rhythmogenesis and interactions between the respiratory and cardiovascular neuronal control networks. However, little is known about the identity and function of these GABAergic inhibitory neurons and what determines their activity. In this study we have identified a population of GABAergic neurons in the ventrolateral medulla that receive increased excitatory post-synaptic potentials during inspiration, but also have spontaneous firing in the absence of synaptic input. Using transgenic mice that express GFP under the control of the Gad1 (GAD67) gene promoter, we determined that this population of GABAergic neurons is in …

Effect Of Synthetic Aβ Peptide Oligomers And Fluorinated Solvents On Kv1.3 Channel Properties And Membrane Conductance, Maria I. Lioudyno, Matteo Broccio, Yuri Sokolov, Suhail Rasool, Jessica Wu, Michael T. Alkire, Virginia Liu, J. Ashot Kozak, Philip R. Dennison, Charles G. Glabe, Mathias Lösche, James E. Hall

Neuroscience, Cell Biology & Physiology Faculty Publications

The impact of synthetic amyloid β (1–42) (Aβ_1–42) oligomers on biophysical properties of voltage-gated potassium channels Kv 1.3 and lipid bilayer membranes (BLMs) was quantified for protocols using hexafluoroisopropanol (HFIP) or sodium hydroxide (NaOH) as solvents prior to initiating the oligomer formation. Regardless of the solvent used Aβ_1–42 samples contained oligomers that reacted with the conformation-specific antibodies A11 and OC and had similar size distributions as determined by dynamic light scattering. Patch-clamp recordings of the potassium currents showed that synthetic Aβ_1–42 oligomers accelerate the activation and inactivation kinetics of Kv 1.3 current with no significant effect …

Genetics Of Clusterin Isoform Expression And Alzheimer's Disease Risk, I-Fang Ling, Jiraganya Bhongsatiern, James F. Simpson, David W. Fardo, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

The minor allele of rs11136000 within CLU is strongly associated with reduced Alzheimer's disease (AD) risk. The mechanism underlying this association is unclear. Here, we report that CLU1 and CLU2 are the two primary CLU isoforms in human brain; CLU1 and CLU2 share exons 2-9 but differ in exon 1 and proximal promoters. The expression of both CLU1 and CLU2 was increased in individuals with significant AD neuropathology. However, only CLU1 was associated with the rs11136000 genotype, with the minor "protective" rs11136000T allele being associated with increased CLU1 expression. Since CLU1 and CLU2 are predicted to encode intracellular and secreted …

Essential Role Of Caveolin-3 In Adiponectin Signalsome Formation And Adiponectin Cardioprotection., Yajing Wang, Xiaoliang Wang, Jean-François Jasmin, Wayne Bond Lau, Rong Li, Yuexin Yuan, Wei Yi, Kurt Chuprun, Michael P. Lisanti, Walter J Koch, Erhe Gao, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

METHODS AND RESULTS: Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery; P

CONCLUSIONS: Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.

Y Chromosome Lineages In Men Of West African Descent, Jada Benn Torres, Menahem B. Doura, Shomarka O.Y. Keita, Rick A. Kittles

Pharmacology and Physiology Faculty Publications

The early African experience in the Americas is marked by the transatlantic slave trade from ~1619 to 1850 and the rise of the plantation system. The origins of enslaved Africans were largely dependent on European preferences as well as the availability of potential laborers within Africa. Rice production was a key industry of many colonial South Carolina low country plantations. Accordingly, rice plantations owners within South Carolina often requested enslaved Africans from the so-called “Grain Coast” of western Africa (Senegal to Sierra Leone). Studies on the African origins of the enslaved within other regions of the Americas have been limited. …

Vascular Inflammatory Cells In Hypertension., David G Harrison, Paul J. Marvar, Jens M Titze

Pharmacology and Physiology Faculty Publications

Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients, and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. …

Glucose Decouples Intracellular Ca2+ Activity From Glucagon Secretion In Mouse Pancreatic Islet Alpha-Cells., Sylvain J Le Marchand, David W Piston

Farber Institute for Neuroscience Faculty Papers

The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+)](i)) and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+)](i) and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP) channel activity but not on tetrodotoxin-sensitive Na(+) channels. …

Identification Of The Functional Binding Pocket For Compounds Targeting Small-Conductance Ca²⁺-Activated Potassium Channels., Miao Zhang, John M Pascal, Marcel Schumann, Roger S Armen, Ji-Fang Zhang

Department of Molecular Physiology and Biophysics Faculty Papers

Small- and intermediate-conductance Ca(2+)-activated potassium channels, activated by Ca(2+)-bound calmodulin, have an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potential for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-ethyl-2-benzimidazolinone (1-EBIO) class is located at the calmodulin-channel interface. …

Ayx1 Dna-Decoy Compound Prevents The Maintenance Of Pain After Incisional, Inflammatory Or Neuropathic Injury, Julien Mamet, Michael Klukinov, Shelle A. Malkmus, Renee R. Donahue, Samantha Williams, Bradley K. Taylor

Renee R. Donahue

The persistence of pain following surgery or trauma limits recovery, physical rehabilitation and the return to a normal quality of life. AYX1 is a compound developed for preventing the maintenance of post-surgical pain with a single intrathecal administration prior to surgery. Post-surgical pain arises from a combination of mechanical/incisional, inflammatory and often nerve trauma. Early in the development of pain following such injury, there are waves of gene regulation in DRG and spinal cord neurons leading to long-term sensitization and the maintenance of pain over time. These transcriptional events are necessary to the development and maintenance of pain and involve …

Loss Of Renal Allografts Secondary To Candida Vascular Complications In Two Recipients From The Same Donor, Govardhana R. Yannam, Lucile E. Wrenshall, R. Brian Stevens

Neuroscience, Cell Biology & Physiology Faculty Publications

Infections remain a major cause of morbidity and mortality in transplant patients. Organ recipients are also susceptible to donor-derived pathogens and the majority of donor infections are easily treatable. Rarely, some pathogens have produced life-threatening complications by compromising the vascular anastomosis. In this case series we report loss of two kidney allografts secondary to vascular complications due to Candida albicans. Both recipients received grafts from a common donor, in whom Candida bacteremia in the donor was not apparent at the time of organ acceptance but became apparent on delayed cultures.

Electrophysiological Abnormalities In Sod1 Transgenic Models In Amyotrophic Lateral Sclerosis: The Commonalities And Differences, Sherif M. Elbasiouny, Katharina Quinlan, Tahra L. Eissa, Charles J. Heckman

Neuroscience, Cell Biology & Physiology Faculty Publications

Since its first description in 1874 by Charcot, the hallmark feature of ALS is the progressive degeneration of upper and lower motoneurons (Charcot, 1874). In the spinal cord, motoneuron degeneration starts long before symptom onset and advances in a size-related fashion, in which large-size alpha-motoneurons degenerate first followed by small-size alpha-motoneurons (Pun et al., 2006; Hegedus et al., 2007; Hegedus et al., 2008). There are conflicting reports regarding the survival of the smallest-sized spinal motoneurons, the gamma-motoneurons (Swash and Fox, 1974; Sobue et al., 1981). Despite its original description, the neuronal degeneration in ALS is not limited to motoneurons. Recent …

Electronic Nose Based On Independent Component Analysis Combined With Partial Least Squares And Artificial Neural Networks For Wine Prediction, Teodoro Aguilera, Jesús Lozano, José A. Paredes, Francisco J. Alvarez, José I. Suárez

Neuroscience, Cell Biology & Physiology Faculty Publications

The aim of this work is to propose an alternative way for wine classification and prediction based on an electronic nose (e-nose) combined with Independent Component Analysis (ICA) as a dimensionality reduction technique, Partial Least Squares (PLS) to predict sensorial descriptors and Artificial Neural Networks (ANNs) for classification purpose. A total of 26 wines from different regions, varieties and elaboration processes have been analyzed with an e-nose and tasted by a sensory panel. Successful results have been obtained in most cases for prediction and classification.

Vestibular Stimulation Enhances Hippocampal Long-Term Potentiation Via Activation Of Cholinergic Septohippocampal Cells, Leung L. Stan

Physiology and Pharmacology Publications

Vestibular stimulation induced acetylcholine release in the hippocampus, and acetylcholine is known to facilitate long-term potentiation (LTP) in the hippocampus. Thus, we hypothesize that vestibular stimulation enhances LTP in CA1 in freely behaving rats, and this enhancement depends on the activation of septohippocampal cholinergic neurons. Field excitatory postsynaptic potentials were recorded in CA1 area of behaving rats following stimulation of the basal dendritic afferents. LTP was induced by a single stimulation train (100 pulses at 200 Hz) during passive whole-body rotation or during awakeimmobility. LTP induced during rotation was significantly larger than that induced during immobility. Pretreatment with cholinergic antagonist …

Durand Et Al 2012 Supplemental Figures, M. Durand, Svetlana V. Komarova, Ajay Bhargava, Keying Li, Cara Fiorino, Osama Maria, Noushin Nabavi, Morris Manolson, Rene Harrison, S. Jeffrey Dixon, Stephen Sims, Marcin Mizianty, Lukasz Kurgan, Sonia Haroun, Gilles Boire, Maria Lucena-Fernandes, Artur De Brum-Fernandes

Physiology and Pharmacology Publications

Objective. Our objective was to compare the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) from patients with osteoarthritis (OA) to that of PBMCs from self-reported normal individuals.

Methods. PBMCs from 140 patients with OA and 45 healthy donors were assayed for CD14⁺ expression and induced to differentiate into osteoclasts (OCs) over 3 weeks in vitro. We assessed the number of the OCs, their resorptive activity, OC apoptosis, and expression of the following cytokine receptors: receptor activator of nuclear factor κB (RANK), interleukin-1 receptor type I (IL-1R1) and IL-1R2. A ridge logistic regression classifier was developed …

Tracing Notochord-Derived Cells Using A Noto-Cre Mouse: Implications For Intervertebral Disc Development., Matthew R Mccann, Owen J Tamplin, Janet Rossant, Cheryle A Séguin

Physiology and Pharmacology Publications

Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and …

A Diet Enriched In Stearic Acid Protects Against The Progression Of Type 2 Diabetes In Leptin Receptor Deficient Mice (Db/Db), Valerie Lynn Reeves

Theses and Dissertations--Physiology

Dietary saturated fat intake contributes to diabetes and cardiovascular disease, as shown in numerous animal and human studies. However, the hypothesis that stearic acid, a saturated fat, has beneficial effects on these conditions has not been adequately tested. Leptin receptor deficient mice (db/db) and wild-type mice were fed either chow or a high fat diet enriched in either stearic acid or oleic acid for ten weeks. The progression of diabetes was evaluated with blood glucose, insulin, and metabolic parameter measurements. At the conclusion of the study, pancreatic islet organization was examined, and blood, liver and feces were assayed for fatty …

Inflammatory Interactions And Secretion In Cardiac Remodeling, Fanmuyi Yang

Theses and Dissertations--Physiology

Heart failure contributes to nearly 60,000 deaths per year in the USA and is often caused by hypertension and preceded by the development of left ventricular hypertrophy (LVH). LVH is usually accompanied by intensive interstitial and perivascular fibrosis which may contribute to arrhythmogenic sudden cardiac death. Emerging evidence indicates that LV dysfunction in patients and animal models of cardiac hypertrophy is closely associated with perivascular inflammation.

To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of pressure-overload-induced LVH: transverse aortic constriction (TAC). Early perivascular inflammation …

Reconstruction Of Nigrostriatal Pathway In An Animal Model Of Parkinson's Disease, Chen Zhang

Theses and Dissertations--Physiology

Parkinson's disease is characterized by progressive degeneration of substantia nigra (SN) and subsequently loss of the nigrostriatal circuit. Many strategies have attempted to reconstruct this circuit but failed to satisfy clinical trials. The inhibitory environment of the adult CNS and the long distance between the SN and the striatum make true reconstruction difficult. To reconstruct this circuit, we used a transplant-pathway targeting model. Several putative pathway targeting molecules were examined for their ability to direct the growth of axons from a dopaminergic transplant. For a proof-of-principle study, adenoviral and lentiviral encoded glial cell line-derived neurotrophic factor (GDNF), GDNF-receptor alpha1 (GFRa1 …