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This paper explores the numerous challenges materials scientists and engineers face, from the time it takes to bring new materials to market to the difficulties delivering suitable formulations and testing against specified criteria, and how those can be resolved.
Extracellular signal-regulated kinase (ERK) is a key component in the regulation of embryogenesis, cell differentiation, cell proliferation, and cell death. The ERK signaling pathway is altered in various cancer types and is frequently investigated as a target for therapeutic intervention. This application note describes how a live cell FRET assay to study ERK signaling was performed on the Operetta CLS™ high-content analysis system. The optimized design of the FRET-based biosensor, the high-quality imaging of the Operetta CLS system and the easy-to-use image analysis tools of the Harmony® software contribute to the robustness of the high-content assay.
The promise of high-content screening is the acceleration of discovery by extracting as much relevant information as possible from cells. Nevertheless, a large percentage of high-content screens analyze only a small number of image-based properties. As a result, valuable information from precious cells and disease models is not utilized. As nearly all screening approaches require a nuclear counterstain such as Hoechst to facilitate segmentation, phenotypic profiling of the nuclei can offer new and additional perspectives on assays at no extra cost.
Cells constantly sense their environment and their response is a spatio-temporal summation of all signals. To maintain physiological stability, cells need to adjust to environmental changes, a process called homeostasis. One of the most important processes involved in maintaining homeostasis is autophagy, and its significance was recognized by the award of the Nobel Prize for Physiology in 2016 to Yoshinori Ohsumi for the discovery of its underlying mechanisms. Although this is not fully understood, it is believed that autophagy can prevent tumor development by degrading, for example, damaged organelles and protein aggregates.
Learn how a phenotypic screening assay to study time-dependent effects of endothelin-1-induced hypertrophy was set up using human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes. Learn how: The Opera Phenix system has been applied in the field of neurodegenerative diseases. In this assay, the Opera Phenix system is 4 times faster than the previous Opera® system. Primary neuron morphology is analyzed in a straightforward approach using Harmony software. Careful assay optimization can increase throughput, and minimize the data burden, without compromising assay performance.
Fundamental processes in living cells, such as apoptosis and signal transduction are controlled by proteins, often acting in concert with other protein partners through protein-protein interactions (PPIs). Inappropriate protein-protein recognition can fundamentally contribute to many diseases, including cancer. Therefore, inhibiting protein-protein interactions represents an emerging area in drug design.
Osteoarthritis (OA) is the most common form of arthritis and affects a considerable portion of the elderly population. In the U.S., it is estimated that more than 630 million people worldwide have this chronic condition, generally in the knees. OA occurs when the cartilage that cushions the ends of bones within the joints gradually deteriorates, causing synovitis and joint deformation.
The goal of OA research is to identify new therapeutic strategies that could prevent, reduce, halt progression, or repair the existing damage to the joint. Non-invasive in vivo imaging such as microCT is the standard modality for bone research due to its ability to obtain high-resolution images at an x-ray dose low enough as not to harm the animal. This makes microCT ideal for monitoring disease progression and response to treatments in the same animal over time. However, microCT data visualization and analysis can be cumbersome and time consuming. In this application note, we compared standard microCT software and advanced bone software to investigate bone erosion in an OA rat model.
X-ray CT imaging is commonly used for skeletal imaging as bones are densely mineralized tissues with excellent x-ray attenuation properties. In contrast, soft, less dense tissues often prove to be challenging to image due to their lack of sufficient tissue density. Soft tissues such as muscle, blood vessels and internal organs share similar x-ray attenuation characteristics and are not distinguishable under typical CT settings. In order to introduce density that would improve soft tissue contrast, several contrast agents have been developed for use in clinical and preclinical settings. This application note outlines the use of iodine and nanoparticle-based contrast agents for imaging soft tissues and vasculature in various organs using the Quantum GX to gain further insights into disease and therapeutic response.
Analyzing transport of biliary metabolites is essential to predict pharmacokinetics and hepatotoxicity during drug development. A functional impairment of hepatobilary transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP-2), is strongly associated with an increased risk of cholestatic liver injury. Here, we describe a 3D high-content screening assay to study hepatobiliary transporter function in InSphero human liver microtissues. Confocal imaging and automated image analysis were used to quantify BSEP and MRP-2-mediated efflux of fluorescent substrates into bile canaliculi.
One of the greatest challenges in multiple sclerosis (MS) therapy is the halting or reversal of the failure of remyelination in the brain in order to reverse disabilities in MS patients. This case study highlights the recent work of Dr. Paul Tesar and colleagues at the Case Western Reserve University School of Medicine, which could potentially lead to such novel treatments, as it aims to control the function of stem cells in the body and thereby to help the body repair itself.