Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII) Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36)

AII amacrine cells are essential interneurons of the primary rod pathway and transmit rod-driven signals to ON cone bipolar cells to enable scotopic vision. Gap junctions made of connexin36 (Cx36) mediate electrical coupling among AII cells and between AII cells and ON cone bipolar cells. These gap junctions underlie a remarkable degree of plasticity and are modulated by different signaling cascades. In particular, Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been characterized as an important regulator of Cx36, capable of potentiating electrical coupling in AII cells. However, it is unclear which CaMKII isoform mediates this effect. To obtain a more detailed understanding of the isoform composition of CaMKII at retinal gap junctions, we analyzed the retinal distribution of all four CaMKII isoforms using confocal microscopy. These experiments revealed a differential distribution of CaMKII isoforms: CaMKII-α was strongly expressed in starburst amacrine cells, which are known to lack electrical coupling. CaMKII-β was abundant in OFF bipolar cells, which form electrical synapses in the outer and the inner retina. CaMKII-γ was diffusely distributed across the entire retina and could not be assigned to a specific cell type. CaMKII-δ labeling was evident in bipolar and AII amacrine cells, which contain the majority of Cx36-immunoreactive puncta in the inner retina. We double-labeled retinas for Cx36 and the four CaMKII isoforms and revealed that the composition of the CaMKII enzyme differs between gap junctions in the outer and the inner retina: in the outer retina, only CaMKII-β colocalized with Cx36-containing gap junctions, whereas in the inner retina, CaMKII-β and -δ colocalized with Cx36. This finding suggests that gap junctions in the inner and the outer retina may be regulated differently although they both contain the same connexin. Taken together, our study identifies CaMKII-β and -δ as Cx36-specific regulators in the mouse retina with CaMKII-δ regulating the primary rod pathway

Cell therapy in dilated cardiomyopathy: from animal models to clinical trials

Dilated cardiomyopathy can be the end-stage form and common denominator of several cardiac disorders of known cause, such as hypertensive, ischemic, diabetic and Chagasic diseases. However, some individuals have clinical findings, such as an increase in ventricular chamber size and impaired contractility (classical manifestations of dilated cardiomyopathy) even in the absence of a diagnosed primary disease. In these patients, dilated cardiomyopathy is classified as idiopathic since its etiology is obscure. Nevertheless, regardless of all of the advances in medical, pharmacological and surgical procedures, the fate of patients with dilated cardiomyopathy (of idiopathic or of any other known cause) is linked to arrhythmic episodes, severe congestive heart failure and an increased risk of sudden cardiac death. In this review, we will summarize present data on the use of cell therapies in animal models of dilated cardiomyopathies and will discuss the few clinical trials that have been published so far involving patients affected by this disease. The animal models discussed here include those in which the cardiomyopathy is produced by genetic manipulation and those in which disease is induced by chemical or infectious agents. The specific model used clearly creates restrictions to translation of the proposed cell therapy to clinical practice, insofar as most of the clinical trials performed to date with cell therapy have used autologous cells. Thus, translation of genetic models of dilated cardiomyopathy may have to wait until the use of allogeneic cells becomes more widespread in clinical trials of cell therapies for cardiac diseases

Aging and ca2+ signaling in murine mesenteric arterial myocytes

This meeting abstract discusses Aging and ca2+ signaling in murine mesenteric arterial myocytes

Functional Modeling Of A Starter Motor

One traditional solution to start an internal combustion engine is the starter motor. Since its conception little was changed in its operational dynamics, even after passing by several design optimization processes. This fact elapses from the absence of application of an analysis tool capable to express the existing relations between its subgroups and the functions that these play. The main goal of the present work is to get a complete mapping of all the functions, components and flows of information and energy, through the application of an existing methodology of analysis, known for "function structure technique", on the described product. Therefore, this mapping will supply a better understanding of the product architecture. First of all, the composed system for the starter motor is divided hierarchically in subsystems according to the existing assemblies. The operation chain is then separated through static and dynamic inspections during its use in the combustion engine. This chain will supply enough knowledge to establish the general functions of the starters. After that, the function structure is divided in two phases: an intermediate level, for partial functions, and a deeper one, with the elementary functions, which is accomplished from physical processes analysis in the mechanisms of the starter. The achieved results will make possible a systematic change in the concept of the product in order to make possible a functional optimization. Copyright © 2008 SAE International.Alternators and Starter Motors (2003) The Bosch Yellow Jackets, , BOSCH Group, editionPahl, G., Beitz, W., Feldhusen, J., Grote, K.-H., (2005) Desing in Engineering, , Edgard Blücher Publishing companyFranke, H.-J., Deimel, M., Selecting and Combining Methods for Complex Problem Solving within the Design Process (2004) International Design Conference, , Dubrovnik, May 18-21Shan, H.-B., Liu, J.-H., Function-and Graph-based Product Principle Structure Modeling and Optimization Method for Conceptual Design (2004) Journal of the Chinese Institute of Industrial Engineers, 21 (5), pp. 484-493El-Haik, (2005) Axiomatic Quality: Integrating Axiomatic Design with Six-Sigma, Reliability, and Quality Engineering Basem, p. 312Scalice, R.K., Forcellini, F., Back, N., New Contributions to the Design of Modular Products-Proposal of a Methodological Approach (2001) Brazilian Congress of Engineering Mechanics, , 16o. Uberlândia. Annals of XVI COBEM, 2001Zhao, Z., Summers, J.D., Vargas-Hernández, N., Shah, J.J., Lacroix, Z., Comparative Study of Representation Structures for Modeling Function and Behavior of Mechanical Devices (2001) ASME 2001 Design Engineering Technical Conferences and Computers and Information in Engineering Conference, , Pittsburgh, Pennsylvania, September 9-12Pahl, G., Beitz, W., (1996) Engineering Design: A Systematic Approach, , edited by Wallace, K. 2nd ed. Springer-VerlagKarnopp, D., Margolis, D., Rosemberg, R., (2000) System Dynamics, Modeling and Simulation of Mechanical Systems, , 3rd Ed. John Wiley & Sons, New YorkCarazzato, M., Project of Automotives Components based on Modularity (2008) Engineering Mechanics, , Master degree thesis)-State University of CampinasAmaral, D., Methodology, Systematization and Election of Projects of Epicicloidais Transmissions with One and Two on TEPS (2000) Engineering Mechanics, , PhD Thesis)-State University of Campinas, Coordination of Perfectioning of Staff of Superior Leve