No abstract

No abstract

No abstract

No abstract

No abstract

Bcl-2 family proteins, known for their apoptosis functioning at the mitochondria, have been shown to localize to other cellular compartments to mediate calcium (Ca2+) signals. Since the proper supply of Ca2+ in cells serves as an important mechanism for cellular survival and bioenergetics, we propose an integrating role for Bcl-2 family proteins in modulating Ca2+ signaling. The endoplasmic reticulum (ER) is the main Ca2+ storage for the cell and Bcl-2 family proteins competitively regulate its Ca2+ concentration. Bcl-2 family proteins also regulate the flux of Ca2+ from the ER by physically interacting with inositol 1,4,5-trisphosphate receptors (IP3Rs) to mediate their opening. Type 1 IP3Rs reside at the bulk ER to coordinate cytosolic Ca2+ signals, while type 3 IP3Rs reside at mitochondria-associated ER membrane (MAM) to facilitate mitochondrial Ca2+ uptake. In healthy cells, mitochondrial Ca2+ drives pyruvate into the citric acid (TCA) cycle to facilitate ATP production, while a continuous accumulation of Ca2+ can trigger the release of cytochrome c, thus initiating apoptosis. Since multiple organelles and Bcl-2 family proteins are involved in Ca2+ signaling, we aim to clarify the role that Bcl-2 family proteins play in facilitating Ca2+ signaling and how mitochondrial Ca2+ is relevant in both bioenergetics and apoptosis. We also explore how these insights could be useful in controlling bioenergetics in apoptosis-resistant cell lines.

No abstract

This article first provides a brief review of the status of the subfield of threedimensional (3D) materials analyses that combine serial sectioning, electron backscatter diffraction (EBSD), and finite element modeling (FEM) of materials microstructures, with emphasis on initial investigations and how they led to the current state of this research area. The discussions focus on studies of the mechanical properties of polycrystalline materials where 3D reconstructions of the microstructureincluding crystallographic orientation information-are used as input into image-based 3D FEM simulations. The authors' recent work on a β-stabilized Ti alloy is utilized for specific examples to illustrate the capabilities of these experimental and modeling techniques, the challenges and the solutions associated with these methods, and the types of results and analyses that can be obtained by the close integration of experiments and simulations.as 50 nm with volumes as large as 100 µm on a side. 10,13 Furthermore, as a result of the advances made in computational hardware and software for 3D reconstruction of multiple serial sections, the analysis and rendering of 3D reconstructions have become more widely available.More recently, electron backscatter diffraction (EBSD) techniques, 14,15 which allow for determination of the local crystal orientation in the scanning electron microscope (SEM), have been combined with serial sectioning methods to provide the crystallographic information for each grain and second-phase crystal in the fully reconstructed 3D microstructures (e.g., see References 1, 12, and 13). Along with the development of such robust 3D experimental data sets, a relatively new type of microstructural modelingtermed 3D image-based modeling 16,17 -has emerged. In the present context, "image-based modeling" refers to a methodology whereby real, experimentally determined 3D microstructures are used as the initial input into models of microstructural response and evolution. The response of the reconstructed microstructures to simulated externally applied mechanical or thermal loads is then determined. This article specifically focuses on 3D image-based finite element modeling (FEM) of microstructural response to applied loads.The purpose of this article is first to review briefly a relatively new subtopic in the 3D analysis of materials: the combination of 3D reconstruction by serial sectioning with EBSD analysis and image-based FEM of the mechanical response of 3D microstructures. Then, one specific example is described to illustrate some of the details and capabilities of the related experimental and modeling techniques in this field. An article by Kammer et al. in this issue focuses on combining simulations of microstructural evolution with experimental serial sectioning results, and another by Buffière et al. discusses FEM modeling based on 3D data sets with a broader overview of applications, including cellular materials and crack propagation. Combining Serial Sectioning with EBSDThe majority of experimental investiga...