In cells experiencing unrelieved endoplasmic reticulum (ER) stress, the ER transmembrane kinase/endoribonuclease (RNase)-IRE1α-endonucleolytically degrades ER-localized mRNAs to promote apoptosis. Here we find that the ABL family of tyrosine kinases rheostatically enhances IRE1α's enzymatic activities, thereby potentiating ER stress-induced apoptosis. During ER stress, cytosolic ABL kinases localize to the ER membrane, where they bind, scaffold, and hyperactivate IRE1α's RNase. Imatinib-an anti-cancer tyrosine kinase inhibitor-antagonizes the ABL-IRE1α interaction, blunts IRE1α RNase hyperactivity, reduces pancreatic β cell apoptosis, and reverses type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse model. A mono-selective kinase inhibitor that allosterically attenuates IRE1α's RNase-KIRA8-also efficaciously reverses established diabetes in NOD mice by sparing β cells and preserving their physiological function. Our data support a model wherein ER-stressed β cells contribute to their own demise during T1D pathogenesis and implicate the ABL-IRE1α axis as a drug target for the treatment of an autoimmune disease.
It is an open source image processing Java program designed for scientific multidimensional images. This open platform for scientific image analysis is used in life sciences.
Image J has been transformed to ImageJ2 application.
This new application improves ImageJ data engine to be sufficient to analyze modern datasets and makes the addition of new functionality possible and provides a framework for interoperability between a plethora of external image visualization and analysis programs.
ImageJ2 strengthens ImageJ’s utility by: 1) generalizing the ImageJ data model; 2) introducing a robust architecture instrumental in building bridges across a range of other image processing tools; 3) remaining open source and cross-platform with permissive licensing, enabling continued widespread adoption and extension; 4) building on the huge collection of existing ImageJ plugins while enabling the creation of new plugins with more powerful features; and 5) leveraging a correspondingly large and diverse community to foster a collaborative and interdisciplinary project that facilitates the collective advancement of science.
Statistical software package for data analysis, hypothesis testing, and modeling. The software can capable perform mathematical calculations (including biostatistics) and graphical plotting such as curve fitting (nonlinear regression) and scientific graphing.
SciCrunch is a data sharing and display platform. Anyone can create a custom portal where they can select searchable subsets of hundreds of data sources, brand their web pages and create their community. SciCrunch will push data updates automatically to all portals on a weekly basis. User communities can also add their own data to SciCrunch, however this is not currently a free service.