https://blogs.helsinki.fi/neurobiology/files/2014/09/Neuron_review_Blaesse2009.pdf

Cation-chloride cotransporters and neuronal function.

Ca2+-ATPases (pumps) are key actors in the regulation of Ca2+ in eukaryotic cells and are thus essential to the correct functioning of the cell machinery They have high affinity for Ca2+ and can efficiently regulate it down to very low concentration levels Two of the pumps have been known for decades (the SERCA and PMCA pumps); one (the SPCA pump) has only become known recently Each pump is the product of a multigene family, the number of isoforms being further increased by alternative splicing of the primary transcripts The three pumps share the basic features of the catalytic mechanism but differ in a number of properties related to tissue distribution, regulation, and role in the cellular homeostasis of Ca2+ The molecular understanding of the function of the pumps has received great impetus from the solution of the three-dimensional structure of one of them, the SERCA pump These spectacular advances in the structure and molecular mechanism of the pumps have been accompanied by the emergence and rapid expansion of the topic of pump malfunction, which has paralleled the rapid expansion of knowledge in the topic of Ca2+-signaling dysfunction Most of the pump defects described so far are genetic: when they are very severe, they produce gross and global disturbances of Ca2+ homeostasis that are incompatible with cell life However, pump defects may also be of a type that produce subtler, often tissue-specific disturbances that affect individual components of the Ca2+-controlling and/or processing machinery They do not bring cells to immediate death but seriously compromise their normal functioning

Calcium Pumps in Health and Disease

Electrical activity in neurons requires a seamless functional coupling between plasmalemmal ion channels and ion transporters. Although ion channels have been studied intensively for several decades, research on ion transporters is in its infancy. In recent years, it has become evident that one family of ion transporters, cation-chloride cotransporters (CCCs), and in particular K(+)-Cl(-) cotransporter 2 (KCC2), have seminal roles in shaping GABAergic signalling and neuronal connectivity. Studying the functions of these transporters may lead to major paradigm shifts in our understanding of the mechanisms underlying brain development and plasticity in health and disease.

Cation-chloride cotransporters in neuronal development, plasticity and disease

Dopamine is synonymous with reward and motivation in mammals. However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies. Instead, octopamine has historically been considered to be the signal for reward in insects. Here we show, using temporal control of neural function in Drosophila, that only short-term appetitive memory is reinforced by octopamine. Moreover, octopamine-dependent memory formation requires signalling through dopamine neurons. Part of the octopamine signal requires the α-adrenergic-like OAMB receptor in an identified subset of mushroom-body-targeted dopamine neurons. Octopamine triggers an increase in intracellular calcium in these dopamine neurons, and their direct activation can substitute for sugar to form appetitive memory, even in flies lacking octopamine. Analysis of the β-adrenergic-like OCTβ2R receptor reveals that octopamine-dependent reinforcement also requires an interaction with dopamine neurons that control appetitive motivation. These data indicate that sweet taste engages a distributed octopamine signal that reinforces memory through discrete subsets of mushroom-body-targeted dopamine neurons. In addition, they reconcile previous findings with octopamine and dopamine and suggest that reinforcement systems in flies are more similar to mammals than previously thought.

https://kops.uni-konstanz.de/bitstream/handle/123456789/28902/Burke_289022.pdf;sequence=2

Layered reward signalling through octopamine and dopamine in Drosophila

Background—Nuclear reprogramming provides an emerging strategy to produce embryo-independent pluripotent stem cells from somatic tissue. Induced pluripotent stem cells (iPS) demonstrate aptitude for de novo cardiac differentiation, yet their potential for heart disease therapy has not been tested. Methods and Results—In this study, fibroblasts transduced with human stemness factors OCT3/4, SOX2, KLF4, and c-MYC converted into an embryonic stem cell–like phenotype and demonstrated the ability to spontaneously assimilate into preimplantation host morula via diploid aggregation, unique to bona fide pluripotent cells. In utero, iPS-derived chimera executed differentiation programs to construct normal heart parenchyma patterning. Within infarcted hearts in the adult, intramyocardial delivery of iPS yielded progeny that properly engrafted without disrupting cytoarchitecture in immunocompetent recipients. In contrast to parental nonreparative fibroblasts, iPS treatment restored postischemic contractile performance, ventricular wall thickness, and electric stability while achieving in situ regeneration of cardiac, smooth muscle, and endothelial tissue. Conclusions—Fibroblasts reprogrammed by human stemness factors thus acquire the potential to repair acute myocardial infarction, establishing iPS in the treatment of heart disease. (Circulation. 2009;120:408-416.)

Repair of Acute Myocardial Infarction by Human Stemness Factors Induced Pluripotent Stem Cells

Deformations and stresses have been determined experimentally in a pin-loaded tube configuration comprising two adjacent and identical hole pairs with fitted pins in a cylindrical tube. The tube was loaded in axial tension applied through one or both of the pins; both parallel and crossed (i.e. perpendicular) pin-axis combinations have been studied. The results are presented in non-dimensional form and discussed. Results are also given for two typical pin-tube configurations subjected, in turn, to axial tension, axial compression, bending in the plane containing the axes of the tube and pin, and torsion about the tube axis.

Deformations and stresses in pin-loaded tubes: Multiple holes and effects of various loadings

Photoelastic Stress Analysis of a Leaf-spring Eyelet

Tablet thickness variations and machine stiffness

A modified weibull analysis for fracture test data of tablets which vary in volume and density

In the paper the theory is presented and the practical application of the technique demonstrated. Issues such as non-adiabatic behaviour and local reinforcement are discussed in detail. An experimental validation is carried out using a specially designed test specimen. The paper focuses on the design of the validation specimen and the discussion of the results obtained from this specimen.

Peter Stanley

Papers

Deformations and stresses in pin-loaded tubes: Multiple holes and effects of various loadings

Photoelastic Stress Analysis of a Leaf-spring Eyelet

Tablet thickness variations and machine stiffness

A modified weibull analysis for fracture test data of tablets which vary in volume and density

An experimental approach to stress separation in thermoelastic stress analysis