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Archive - Apr 7, 2015

Totally New & Unexpected Angle in Diabetes--Leaky RyR2 Calcium Channels Reduce Insulin Release from Beta Cells and Cause High Blood Sugar; Leaks Can Be Stopped and Glucose Levels Normalized in Mouse Model

A cellular defect that can impair the body's ability to handle high glucose levels and could point the way to a potential new treatment for diabetes has been identified by Columbia University Medical Center (CUMC) researchers. The CUMC team found that ryanodine receptor type 2 (RyR2) calcium channels in insulin-producing cells play an important and previously underappreciated role in glucose balance. RyR2 channels control intracellular calcium release. When leaky, they were found to reduce insulin release from the pancreas, resulting in high blood sugar levels in a test that measures the ability to regulate glucose. The researchers also demonstrated, in a mouse model of diabetes, that these leaks can be stopped and glucose levels normalized with an experimental drug called Rycal. The findings were published online on April 6, 2015 in an open-access article in the Journal of Clinical Investigation. The article is titled, "Calcium Release Channel RyR2 Regulates Insulin Release and Glucose Homeostasis." "We've known that calcium in the pancreatic beta cells plays a significant role in regulating insulin secretion, but calcium levels were thought to be controlled largely by the entry of calcium into the cell," said senior author Andrew R. Marks, M.D., Professor and Chair of Physiology and Cellular Biophysics at CUMC. "It turns out that there's another mechanism in pancreatic beta cells that also controls calcium. This mechanism involves RyR2 channels, and leaks in these channels can lead to impaired glucose tolerance.

Acoustic Tweezers Used to Separate Circulating Tumor Cells from Blood

Separating circulating cancer cells from blood cells for diagnostic, prognostic, and treatment purposes may become much easier using an acoustic separation method and an inexpensive, disposable chip, according to a team of engineers. "Looking for circulating tumor cells (CTCs) in a blood sample is like looking for a needle in a haystack," said Dr. Tony Jun Huang, Professor of Engineering Science and Mechanics at Penn State. "Typically, the CTCs are about one in every one billion blood cells in the sample." Existing methods of separation use tumor-specific antibodies to bind with the cancer cells and isolate them, but require that the appropriate antibodies be known in advance. Other methods rely on size, deformability, or electrical properties. Unlike conventional separation methods that centrifuge for 10 minutes at 3,000 revolutions per minute, surface acoustic waves can separate cells in a much gentler way with a simple, low-cost device. Acoustic-based separations are potentially important because they are non-invasive and do not alter or damage cells. However, in order to be effective for clinical use, they also need to be rapidly and easily applicable. "In order to significantly increase the throughput for capturing those rare CTCs, device design has to be optimized for much higher flow rates and longer acoustic working length," said Dr. Ming Dao, Principal Research Scientist, Materials Science, and Engineering, at MIT. "With an integrated experimental/modeling approach, the new generation of the device has improved cell sorting throughput more than 20 times higher than previously achieved and made it possible for us to work with patient samples." The researchers worked both experimentally and with models to optimize the separation of CTCs from blood.

Bumblebees Differentiate Flower Types Arranged Horizontally, But Not Vertically

It is well known that bumblebees and other pollinators can tell the difference between plants that will provide them with nectar and pollen and those that will not. However, until now, little has been known about how the arrangement of flowers affects the pollinators’ decision-making. Researchers from the School of Biological and Chemical Sciences at Queen Mary University of London, taught bumblebees to distinguish between two visually clearly different feeder types, one type contained food, while the other did not. The researchers found that bees were able to quickly learn the feeder types containing food when the feeders were arranged horizontally. However, the bees failed to distinguish these feeder types when they were distributed vertically on a wall and significantly more often chose the wrong feeder type. The results were published online on March 6, 2015 in Behavioral Ecology. The article is titled “Bumblebees Utilize Floral Cues Differently on Vertically and Horizontally Arranged Flowers.” The researchers are certain that the bees were equally able to discriminate between the two presented feeders in both arrangements, but simply chose not to waste the brain power doing so on vertically arranged feeders. They believe that this is because in a meadow typically rewarding and unrewarding flowers of different species grow side-by-side and bees benefit from visiting only flowers similar to the ones that have previously rewarded them. In contrast, vertically clustered flowers, such as on flowering bushes or trees, the flowers in the arrangement are typically the same and paying close attention to the flower features may not be needed. Dr Stephan Wolf, co-author of the research, said: “This is a rare example of a pollinator being able to tell the difference between different flowers, but simply choosing not to do so.

MGH Study ID’s Protein (TREML4) That Triggers Lupus-Associated TLR7-Mediated Immune System Activation; New Target for Possible Disease Treatment

Massachusetts General Hospital (MGH) investigators have identified an inflammatory molecule that appears to play an essential role in the autoimmune disorder systemic lupus erythematosus (SLE), commonly known as lupus. In their report, which was published online on April 6, 2015 in Nature Immunology, the researchers describe finding that a protein that regulates certain cells in the innate immune system - the body's first line of defense against infection - activates a molecular pathway known to be associated with lupus and that the protein's activity is required for the development of lupus symptoms in a mouse model of the disease. "This study is the first demonstration that the receptor TREML4 amplifies the cellular responses transmitted through the TLR7 receptor (toll-like receotor 7) and that a lack of such amplification prevents the inflammatory overactivation underlying lupus," says Terry Means, Ph.D., of the Center for Immunology and Inflammatory Diseases in the MGH Division of Rheumatology, Allergy, and Immunology. "Our preliminary results suggest that TREML4-regulated signaling through TLR7 may be a potential drug target to limit inflammation and the development of autoimmunity." Lupus is an autoimmune disorder characterized by periodic inflammation of joints, connective tissues, and organs, including heart, lungs, kidneys, and brain. TLR7 is one of a family of receptors present on innate immune cells like macrophages that have been linked to chronic inflammation and autoimmunity. Animal studies have suggested that overactivation of TLR7 plays a role in lupus, and a gene variant that increases expression of the receptor has been associated with increased lupus risk in human patients. The current study was designed to identify genes for other molecules required for TLR7-mediated immune cell activation.