The Global ECT-MRI Research Collaboration (GEMRIC): Establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy.

Major depression, currently the world's primary cause of disability, leads to profound personal suffering and increased risk of suicide. Unfortunately, the success of antidepressant treatment varies amongst individuals and can take weeks to months in those who respond. Electroconvulsive therapy (ECT), generally prescribed for the most severely depressed and when standard treatments fail, produces a more rapid response and remains the most effective intervention for severe depression. Exploring the neurobiological effects of ECT is thus an ideal approach to better understand the mechanisms of successful therapeutic response. Though several recent neuroimaging studies show structural and functional changes associated with ECT, not all brain changes associate with clinical outcome. Larger studies that can address individual differences in clinical and treatment parameters may better target biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we summarize the ECT sample characteristics from currently participating sites, and the common data-repository and standardized image analysis pipeline developed for this initiative. This includes data harmonization across sites and MRI platforms, and a method for obtaining unbiased estimates of structural change based on longitudinal measurements with serial MRI scans. The optimized analysis pipeline, together with the large and heterogeneous combined GEMRIC dataset, will provide new opportunities to elucidate the mechanisms of ECT response and the factors mediating and predictive of clinical outcomes, which may ultimately lead to more effective personalized treatment approaches

Social Assistance in Developing Countries Database Version 5.0

The Social Assistance in Developing Countries Database is a user-friendly tool that provides summary information on social assistance interventions in developing countries. It provides a summary of the evidence available on the effectiveness of social assistance interventions in developing countries. It focuses on programmes seeking to combine the reduction and mitigation of poverty, with strengthening and facilitating household investments capable of preventing poverty and securing development in the longer term. The inclusion of programmes is on the basis of the availability of information on design features, evaluation, size, scope, or significance. Version 5 of the database updates information on existing programmes and incorporates information on pilot social assistance programmes in Latin America, Asia and Africa. It also adopts a new typology that distinguishes between social assistance programmes providing pure income transfers; programmes that provide transfers plus interventions aimed at human, financial, or physical asset accumulation; and integrated poverty reduction programmes. This new typology has, in our view, several advantages. It is a more flexible, and more accurate, template with which to identify key programme features. It provides a good entry point into the conceptual underpinnings of social assistance programmes

Rat basophilic leukemia cells as model system for inositol 1,4,5-trisphosphate receptor IV, a receptor of the type II family: functional comparison and immunological detection

This study concerns the detection and analysis of the highly homologous type II-like inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3R-II, -IV and -V). We have particularly investigated RBL-2H3 cells, which at the mRNA level predominantly expressed InsP3R-IV [De Smedt H. Missiaen L. Parys JB. et al. (1994) Determination of relative amounts of inositol trisphosphate receptor mRNA isoforms by ratio polymerase chain reaction. J. Biol. Chem., 269, 21691-21698]. When measured in identical experimental conditions, microsomes from RBL-2H3 cells were characterized by a much higher InsP3 binding affinity (Kd 3.8 ± 0.8 nM, Bmax 0.40 ± 0.08 pmol/mg protein) than microsomes from A7r5 cells (Kd 65 ± 7 nM, Bmax 0.65 ± 0.08 pmol/mg protein) or from cerebellum (Kd 135 ± 14 nM, Bmax 7.35 ± 1.13 pmol/mg protein). An affinity-purified antibody against the C-terminus of type II-like InsP3Rs detected, after SDS-PAGE and immunoblotting, a 250 kD protein in RBL-2H3 and C3H10T1/2 cells, but not in other cell types. An isoform-specific antibody against the C-terminus of InsP3R-I was used to determine the presence of the various InsP3R-I splice isoforms at the protein level. The 273 kD (brain), 261 kD (peripheral tissues) and 256 kD (Xenopus oocytes) isoforms were recognized. Expression of InsP3R-I in RBL-2H3 cells was very low. Taken together, our results support the hypothesis that InsP3R isoforms may differ to a large extent in their affinity for InsP3 and suggest that RBL-2H3 cells are a useful model for the study of InsP3R-IV

Slow kinetics of InsP₃-induced Ca²⁺ release: differences between uni- and bi-directional ⁴⁵Ca²⁺ fluxes

The effects of a long-lasting stimulation with inositol 1,4,5-trisphosphate (InsP3) have been studied in monolayers of permeabilized A7r5 cells. When measured under unidirectional 45Ca2+ efflux conditions, i.e. in the presence of 2 μM thapsigargin, an initial fast release was observed which then progressively slowed down into a slow phase which persisted for up to 20 min. When measured under bidirectional 45Ca2+ flux conditions with functional Ca2+ pumps, a transient phase of re-uptake occurred between the initial fast and the subsequent slow release phase. These kinetics are compatible with intrinsic inactivation of the InsP3 receptor. However, this inactivation did not prevent the slow release component. The slow component was not due to the accumulation of an InsP3 metabolite nor to a GTP-dependent translocation of Ca2+ between stores. The slow release phase was more pronounced when the Ca2+ pumps were active than when they were inhibited. This observation is compatible with other findings indicating that the InsP3 receptor is controlled by luminal Ca2+. The decreasing effectiveness of a 20 min lasting InsP3 challenge in mobilizing Ca2+ from less filled stores is most likely due to a progressive depletion of the store and cannot be considered as an experimental artifact caused by a preferential emptying of InsP3-sensitive Ca2+ stores. We conclude that the InsP3 receptor can intrinsically inactivate but that this inactivation is unable to prevent the slow release, which is especially pronounced when Ca2+ pumps are active

Synergism between hypotonically induced calcium release and fatty acyl-CoA esters induced calcium release from intracellular stores

The non-mitochondrial Ca2+ stores in permeabilized A7r5 cells responded to a decrease in Mg-ATP concentration with a pronounced Ca2+ release if 20 mu M CoA was present. This release was rather specific for the preincubation or removal of ATP. ATP gamma S was much less effective and AMP-PNP, GTP, ITP, CTP, UTP, ADP, AMP, adenosine and adenine had no effect. CoA activated with an EC50 of 6 mu M. Dephospho-CoA was a less effective cofactor and desulfo-CoA was ineffective. The release induced by Mg-ATP removal did not occur in the presence of 2% fatty acid-free bovine serum albumin and did not develop at 4 degrees C. All these findings suggest that CoA had to be acylated by endogenous fatty-acyl-CoA synthetase to become effective. Myristoyl-and palmitoyl-CoA esters were identified as the most effective cofactors for the release. Ca2+ release induced by removing Mg-ATP did not occur if the osmolality of the medium was kept constant by addition of mannitol, sucrose, KCl, MgCl2 or Mg-GTP, indicating that the decrease in tonicity was the trigger for the release. Mg-ATP plus CoA also synergized with Ca2+ release induced by a hypotonic shock imposed by diluting the medium with H2O. Osmolality changes induced by decreasing the Mg-ATP concentration were more effective in releasing Ca2+ than equal decreases in concentration of all solutes. We conclude that fatty acyl-CoA esters sensitize the hypotonically induced Ca2+ release from the non-mitochondrial Ca2+ stores