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Pharmacological analysis of dopamine modulation in the Drosophila melanogaster larval heart
Josh S. Titlow, Jenna M. Rufer, Kayla E. King, Robin L. Cooper
Physiol Rep, 1 (2), 2013, e00020, doi: 10.1002/phy2.20
Dopamine (DA) and other neurotransmitters affect nonneuronal tissues in insects by circulating in the hemolymph. In several organisms, DA has been shown to modulate distinct aspects of cardiac function but the signal transduction pathways that mediate dopaminergic effects on the heart are not well characterized. Here, we used a semiintact Drosophila melanogaster larva preparation and drugs targeting DA receptors and canonical second messenger pathways to identify signaling cascades that mediate the effect of DA on a myogenic heart. DA has a positive chronotropic effect that is mimicked by SKF38393 (type-1 DA receptor agonist) and quinpirole (type-2 DA receptor agonist). SCH23390 and spiperone (type-1 and type-2 DA receptor antagonists) are moderately effective at inhibiting DA's effect. An adenylate cyclase inhibitor (SQ,22536) is also effective at blocking the stimulatory effect of DA but the drug has its own dose-dependent effect. Activation of protein kinase C with a diacylglycerol analog has a stimulatory effect on heart rate (HR). These results suggest that (1) both DA receptor subtypes are expressed in third instar larva cardiac myocytes to increase HR in response to rising levels of DA in the hemolymph, and (2) canonical second messenger pathways modulate HR in D. melanogaster larvae. Having these disparate signaling cascades converge toward a common modulatory function appears redundant, but in the context of multiple cardioactive chemicals this redundancy is likely to increase the fidelity of signal transduction.
DREADDs in Drosophila: A Pharmacogenetic Approach for Controlling Behavior, Neuronal Signaling,
Physiology in the Fly
Jaime Becnel, Oralee Johnson, Zana R. Majeed, Vi Tran, Bangning Yu,
Bryan L. Roth, Robin L. Cooper, Edmund K. Kerut, Charles D. Nichols
Cell Reports, Volume 4, Issue 5, 12 September 2013, Pages 1049-1059,
ISSN 2211-1247, http://dx.doi.org/10.1016/j.celrep.2013.08.003.
We have translated a powerful genetic tool, designer receptors exclusively activated by designer drugs (DREADDs), from mammalian systems to Drosophila melanogaster to selectively, rapidly, reversibly, and dose-dependently control behaviors and physiological processes in the fly. DREADDs are muscarinic acetylcholine G protein-coupled receptors evolved for loss of affinity to acetylcholine and for the ability to be fully activated by an otherwise biologically inert chemical, clozapine-N-oxide. We demonstrate its ability to control a variety of behaviors and processes in larvae and adults, including heart rate, sensory processing, diurnal behavior, learning and memory, and courtship. The advantages of this particular technology include the dose-responsive control of behaviors, the lack of a need for specialized equipment, and the capacity to remotely cont-rol signaling in essentially all neuronal and nonneuronal fly tissues.
Automated Image Analysis of Skeletal Muscle Fiber Cross-Sectional Area.
Skeletal Muscle Fiber Cross-Sectional Area. J Appl Physiol. 2012 Nov 8. [Epub ahead of print] PubMed PMID: 23139362.
J. MULA • J.D. LEE • F. LIU • L. YANG • CA PETERSON
Morphological characteristics of muscle fibers, such as fiber size, are critical factors that determine the health and function of the muscle. However, at this time, quantification of muscle fiber cross-sectional area is still a manual or, at best, a semi-automated process. This process is labor intensive, time consuming and prone to errors, leading to high inter-observer variability. We have developed and validated an automatic image segmentation algorithm and compared it directly to commercially available semi-automatic software currently considered state-of-the-art. The proposed automatic segmentation algorithm was evaluated against a semi-automatic method with manual annotation using 35 randomly selected cross-sectional muscle histochemical images. The proposed algorithm begins with ridge detection to enhance the muscle fiber boundaries, followed by robust seed detection based on concave area identification to find initial seeds for muscle fibers. The final muscle fiber boundaries are automatically delineated using a gradient vector flow (GVF) deformable model. Our automatic approach is accurate and represents a significant advancement in efficiency; quantification of fiber area in muscle cross-sections was reduced from 25-40 minutes/image to 15 seconds/image, while accommodating common quantification obstacles including morphological variation (e.g. heterogeneity in fiber size and fibrosis) and technical artifacts (e.g. processing defects and poor staining quality). Automatic quantification of muscle fiber cross-sectional area using the proposed method is a powerful tool that will increase sensitivity, objectivity, and efficiency in measuring muscle adaptation.
Satellite cell depletion does not inhibit adult skeletal muscle regrowth following unloading-induced atrophy
Am J Physiol Cell Physiol October 15, 2012 303:C854-C861; published ahead of print August 15, 2012, doi:10.1152/ajpcell.00207.2012s
JANNA R. JACKSON • JYOTHI MULA • TYLER J. KIRBY • CHRISTOPHER S. FRY • JONAH D. LEE • MARGO F. UBELE • KENNETH S. CAMPBELL • JOHN J. MCCARTHY • CHARLOTTE A. PETERSON • ESTHER E. DUPONT-VERSTEEGDEN
Serotonin and Synaptic Transmission at Invertebrate Neuromuscular Junctions
Exp Neurobiol. 2012 Sep;21(3):101-112.
Published online 2012 September 7. http://dx.doi.org/10.5607/en.2012.21.3.101
WEN-HUI WU • ROBIN L. COOPER
Hip Strengthening Prior to Functional Exercises Reduces Pain Sooner Than Quadriceps Strengthening in Females
With Patellofemoral Pain Syndrome:
A Randomized Clinical Trial
J Orthop Sports Phys Ther. 2011;41(8):560-570. Epub 2011 Jun 7;
KIMBERLY L. DOLAK, MS, ATC1 • CARRIE SILKMAN, MSEd, ATC • JENNIFER MEDINA MCKEON, PhD, ATC, CSCS,
ROBERT G. HOSEY, MD • CHRISTIAN LATTERMANN, MD • TIMOTHY L. UHL, PT, PhD, ATC
Smooth muscle-specific expression of calcium-independent phospholipase A2β (iPLA2β) participates in the initiation and early progression of vascular inflammation and neointima formation.
J Biol Chem. 2012 Jul 13;287(29):24739-53
Liu S, Xie Z, Zhao Q, Pang H, Turk J, Calderon L, Su W, Zhao G, Xu H, Gong MC, Guo Z
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