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Discoveries Category

Key to Islet Cell Differentiation

Jan. 31, 2019—The pancreatic islets of Langerhans are specialized structures containing five distinct types of cells, (α, β, γ, δ, ε), each of which secretes a different hormone (glucagon, insulin, pancreatic polypeptide, somatostatin, and ghrelin, respectively). Understanding the mechanisms that determine the total and relative quantities of these five islet cell types is key to understanding diabetes,...

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Targeting Proteins for Endocytosis

Jan. 23, 2019—One mechanism that cells use to modulate the activity of plasma membrane proteins is to remove them from the surface through endocytosis. However, this mechanism requires that proteins to be removed are correctly identified so that needed membrane functions are not compromised. Ubiquitylation is one way that cells label plasma membrane proteins for endocytosis, though...

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Amplifying the Signal with a Scaffold

Jan. 14, 2019—Scaffolding proteins serve as sites of binding and organization for the multiple components involved in many signaling pathways. Scaffolding promotes key protein-protein interactions and can substantially amplify a signal; however, if proteins are bound too tightly to a scaffold, signal propagation may actually be hindered. The precise mechanisms that regulate the interactions between scaffolding proteins...

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The Fine Points of Exocyst Dynamics

Dec. 17, 2018—Exocytic vesicles fuse with the plasma membrane (PM) through the action of SNARE proteins, which in turn, are delivered to the vesicles by multisubunit protein tethering complexes. One such complex is the exocyst, comprising two tetrameric subcomplexes, SC1 (composed of SEC3, SEC5, SEC6, and SEC8) and SC2 (composed of SEC10, SEC15, EXO70, and EXO84). Prior...

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Keys to Sarcomere Assembly

Dec. 17, 2018—The sarcomere is a repeating unit of interdigitating actin and myosin filaments that serves as the building blocks of the myofibrils in striated muscle cells. Sarcomeres are demarcated at each end by a Z-disc containing α-actinin 2 to which thin fibers of actin are attached. In the center are the A-bands comprising thick filaments composed...

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HMCES: A New Guardian Against DNA Damage

Dec. 14, 2018—In DNA, abasic sites (apurinic/apyrimidinic or AP sites) occur through spontaneous hydrolysis of the glycosidic bond that joins the base to the deoxyribose ring (a common reaction following formation of some kinds of DNA adducts) or through the action of DNA glycosylases during repair of damaged bases. In double-stranded DNA, AP sites are easily repaired...

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New Revelations from Single-Cell Cytomic Data

Dec. 12, 2018—Cytomics, the “omics” of cell identity, offers the opportunity to systematically identify all cells in a tissue or patient sample, and the recent advent of high-dimensional flow and mass cytometry to the cytomics arsenal has markedly increased its power. Cytomics is particularly valuable in the detailed analysis of immune cell populations, which are frequently complex...

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A Close Look at β-Cell Transcription Factor Function

Dec. 4, 2018—Over 27 million people in the United States are living with type 2 (adult onset) diabetes. In most cases, type 2 diabetes results from a mixture of multiple genetic and environmental factors. However, in a small subgroup of patients, mutation of a single gene leads to the form of type 2 diabetes known as maturity...

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How Cancer Cell Death Can Thwart Therapy

Dec. 4, 2018—Apoptosis is a mechanism of cell death that occurs in normal tissues as part of natural cell turnover and remodeling. Apoptotic cells are cleared by efforcytosis, a specialized form of phagocytosis mediated by MerTK, a receptor tyrosine kinase expressed by many phagocytic cells. MerTK recognizes a combination of ligands, such as Gas6, in combination with...

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Exploring Single Cell Data with sc-UniFrac

Oct. 25, 2018—Our growing ability to acquire data at the level of single cells in complex samples provides exciting new opportunities to understand physiological and pathophysiological processes; however, it also presents daunting challenges for the statistical evaluation of the resultant huge datasets. To date, most experimental approaches have focused on identifying the cell populations that are present...

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