Scientists have identified four gene loci newly associated with the severe food allergy eosinophilic esophagitis (EoE). Because the genes appear to have roles in other allergic diseases and in inflammation, the findings may point toward potential new treatments for EoE. "This research adds to the evidence that genetic factors play key roles in EoE, and broadens our knowledge of biological networks that may offer attractive targets for therapy," said study leader Hakon Hakonarson (image), M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia (CHOP). Dr. Hakonarson and colleagues from other hospitals and academic centers published the study online on November 19, 2014 in Nature Communications. The research builds on a 2010 study by Dr. Hakonarson and colleagues that identified TSLP (thymic stromal lymphopoietin ) as the first major gene associated with EoE. Only recently recognized as a distinct condition, EoE has been rapidly increasing in prevalence over the past 20 years. Its hallmark is inflammation and painful swelling in the esophagus, along with high levels of immune cells called eosinophils. It can affect people of any age, but is more common among young men who have a history of other allergic diseases such as asthma and eczema. EoE is often first discovered in children with feeding difficulties and failure to thrive. Because children with EoE are often allergic to many foods, they may be placed on a highly-restricted diet containing no large food proteins, to allow time for their symptoms to resolve. Physicians then perform tests to determine which foods a child can or cannot eat.
On Tuesday, November 18, winners of the 2014 Life Science Industry Awards® were formally announced at the Grand Hyatt Washington in Washington, D.C. The Life Science Industry Awards recognize those life science suppliers that are best-in-class in 28 product and service categories. The awards were presented by BioInformatics LLC, considered by many to be the premier market research and advisory firm serving the life science industry. The event was attended by industry executives and product and marketing professionals from 41 life science companies Using industry best-practices market research methodologies, almost 6,000 scientists were surveyed to reveal preferred suppliers in 28 product, communications, and support categories. These scientists were drawn from BioInformatics LLC’s online panel of scientists, The Science Advisory Board®. From the data collected, BioInformatics LLC analysts calculated an overall score for each nominated company based on the number of nominations received, as well as key measurements of customer satisfaction and loyalty. “The vision and foresight of the companies we honored last night have made possible many of the scientific advances of the past decade,” said Jennifer Cotteleer, CEO of BioInformatics LLC.
Changes to the structure of the histone variant H3.3 may play a key role in silencing genes that regulate cancer cell growth, according to a study led by researchers from the Icahn School of Medicine, Mount Sinai Hospital, in New York City. The results were published online on November 14, 2014 in Nature Communications. According to the authors, this is the first study to identify H3.3 as a key regulator in cellular senescence, a process in which cells stop multiplying. Cellular senescence has garnered significant scientific interest lately because it may be one key to prevent the initiation of cancer. However, little is known about this process and how genes that enable cells to divide and multiply (the cell cycle) are turned off. A growing body of evidence suggests that the process of cellular senescence is driven by changes in the protein complexes called chromatin in the nuclei of cells. Using models of senescence, researchers found that histone variant H3.3, a protein that works closely with chromatin to package and regulate genetic material within cells, and, in particular, the clipped form of this protein, H3.3cs1, help to silence target genes that regulate the cell cycle. Could the presence of this protein stop cells from dividing? Indeed, using genome-wide transcriptional profiling, the researchers discovered that expression of clipped H3.3 (i.e., 3.3cs1) silences genes that regulate the division and duplication of a cell. "Cellular senescence creates a chromatin environment that represses cell multiplication, and thus cell or tumor growth, but how this happens molecularly is what we sought to discover," said lead investigator Emily Bernstein, Ph.D., Department of Oncological Sciences, Icahn School of Medicine, Mount Sinai Hospital.
Research published today found that the investigational drug patiromer decreased high potassium levels and maintained normal potassium levels in patients with chronic kidney disease in a Phase 3 study. The results of the multicenter trial appear today (November 21, 2014) in an open-access article in the New England Journal of Medicine. This article is accompanied by a second open-access article on Phase 3 results for another anti-hyperkalemia drug (ZS-9), as well as by an open-access editorial entitled, “A New Era for the Treatment of Hyperkalemia?” Elevated potassium, a condition called hyperkalemia, increases the risk of death in high-risk patients and limits the use of several types of drugs, called RAAS (renin-angiotensin-aldosterone system) inhibitors, commonly used to control hypertension and cardiovascular disease and to prevent kidney disorders. "Patients with advanced kidney disease are at highest risk for hyperkalemia thanks to a double whammy," says the study's principal investigator, Matthew R. Weir, M.D., Professor of Medicine and Director of the Division of Nephrology at the University of Maryland School of Medicine. "Their kidneys are unable to remove potassium from the body effectively, and the patient may also be taking certain blood pressure control drugs that have been linked to high potassium levels. Current medications for hyperkalemia have gastrointestinal side effects that limit their extended use. We hoped the drug in this study would do the job with minimal side effects." In this Phase 3 study of 237 patients with chronic kidney disease who were receiving RAAS inhibitors, 76 percent of the patients reached the target potassium level after four weeks on patiromer.
One of the most aggressive and common forms of liver cancer is hepatocellular carcinoma. A team of researchers from the Institute of Cancer Research at the Medical University of Vienna (MedUni Vienna) has now identified the crucial factor involved in the development and progression of this malignant type of tumor: namely, the AXL receptor, which supports cancer-promoting processes and slows down cancer-inhibiting factors. This key finding could make a targeted therapeutic approach possible in future. In the Western world, metabolic diseases and infections with hepatitis C are the most common causes of hepatocellular carcinoma (HCC). The team led by Dr. Wolfgang Mikulits, Head of the Tumor Progression and Metastasis Research Group at the MedUni Vienna Institute of Cancer Research (ICR) and member of the Comprehensive Cancer Center (CCC) Vienna, investigated the role of the AXL receptor tyrosine kinase in the context of liver cancer as part of a study. Says Dr. Mikulits: "Until now, the function of AXL had been barely investigated at all, which is astonishing since this receptor is shown to have been activated in more than 50 per cent of all HCC patients." The researchers were able to demonstrate that the expression and activation of AXL lead to a diversion of signaling pathways, enabling the migration and metastasis of liver cancer cells. As a result, AXL, after binding a 14-3-3 adapter protein, is able to influence the extremely important transforming growth factor beta (TGF-beta) signaling pathway in such a way that it only causes the invasion and metastasis of HCC cells. In contrast to this, AXL inhibits the anti-oncogenic function of TGF-beta. AXL is therefore the crucial factor in the aggressive development of hepatocellular carcinoma.
Lou Gehrig's disease, also known as amyotrophic lateral sclerosis (ALS), might damage muscle-controlling nerve cells in the brain earlier in the disease process than previously thought, according to research from the Cedars-Sinai Board of Governors Regenerative Medicine Institute in Los Angeles, California. The new findings, published in the November 19, 2014 issue of the Journal of Neuroscience, could shift researchers' attention from the spinal cord to the brain's motor cortex as the disease's initial point of dysfunction. "In this study, we show the exact progression of ALS in animals that have an inherited form of the disease, and we expose the brain's significant role in initiating the disease process, thought previously to originate in the muscle or spinal cord," said Clive Svendsen, Ph.D., professor and director of the Board of Governors Regenerative Medicine Institute. "We did this by selectively removing the disease-causing mutation just from the brains of ALS animals, and found that this alone had a big impact on disease initiation and progression." ALS causes weakness and gradual paralysis of muscles throughout the body, and although the timing and sequence of progression are unpredictable, the disease often begins in the arms or legs and eventually affects the breathing muscles in the chest. Patients generally live only three to five years after onset. The disease is known to affect motor neurons – nerve cells that control muscles – in the brain, brainstem, and spinal cord. It also inflicts damage in the nerve pathways extending from the spinal cord out to the muscles of the body. Breakdown of communication at the neuromuscular junctions – the points where nerve fibers connect to muscle fibers – is what ultimately leads to muscle weakness and failure.
Between 70 and 80 percent of patients with the connective tissue condition Marfan syndrome have aortic-root dilation, which happens when the aorta, the main blood vessel between the heart and body, becomes too large and tears. This condition can result in serious illness and sometimes death. A National Institutes of Health-funded study comparing treatment with widely used blood pressure medications atenolol or losartan in patients with Marfan syndrome who had an enlarged aortic root found no significant difference in the rate of aortic-root dilation between the two treatment groups over three years. The results of the Atenolol versus Losartan in Children and Young Adults with Marfan Syndrome study, supported by NIH’s National Heart, Lung, and Blood Institute (NHLBI), were presented today at the American Heart Association (AHA) Scientific Sessions in Chicago. The study was published simultaneously today (November 18, 2014) in the New England Journal of Medicine. Marfan syndrome is a genetic disorder that affects connective tissue, which helps to hold the body together. Features of the disorder are most often found in the heart, blood vessels, bones, joints, and eyes. People with the syndrome tend to be extremely tall. Standard care includes frequent cardiac imaging, exercise restriction, administration of a beta-blocker such as atenolol or other medications that may decrease the rate of aortic enlargement, and elective aortic-root replacement when the aortic root becomes too large. Although early diagnosis and refined medical and surgical management have improved survival, patients with Marfan syndrome continue to have high rates of complications and death from heart problems, even at a young age.
A team of scientists specializing in cave biodiversity from the South China Agricultural University (Guangzhou) has unearthed a treasure trove of rare blind cave beetles. The description of seven new species of underground Trechinae beetles, published online on November 14, 2014 in the open-access journal ZooKeys, attests to the Du'an Karst as the most diverse area for these cave dwellers in China. "China is becoming more and more fascinating for those who study cave biodiversity, because it holds some of the most morphologically adapted cavernicolous animals in the world. This is specifically true for fishes and the threchine beetles, the second of which is also the group featured in this study," explains the senior author of the study Professor Mingyi Tian. Like most cavernicolous species, Trechinae cave beetles show a number of specific adaptations, such as lack of eyes and color, which are traits common among cave dwellers. The new Trechinae beetles belong to the genus Dongodytes, whose members are easily recognizable by their extraordinary slender and very elongated body. Members of this genus are usually very rare in caves, with only five species reported from China before now. During the recent study of the cave systems in Du'an Karst, however, this numbers drastically changed, Of the 48 visited caves, 12 held populations of trechine beetles. A total of 103 samples were collected, out of which the team of scientists determined ten different species, seven of which are new to science. "This new discovery casts a new light on the importance of the Du'an Karst as a biological hotspot for cavernicolousTrechinae in China," adds Professor Tian. Image shows a Trechinae beetle.
A novel looping mechanism that involves the end caps of DNA may help explain the aging of cells and how they initiate and transmit disease, according to new research from University of Texas (UT) Southwestern Medical Center cell biologists. The UT Southwestern team found that the length of the endcaps of DNA, called telomeres, form loops that determine whether certain genes are turned off when young and become activated later in life, thereby contributing to aging and disease. “Our results suggest a potential novel mechanism for how the length of telomeres may silence genes early in life and then contribute to their activation later in life when telomeres are progressively shortened. This is a new way of gene regulation that is controlled by telomere length," said Dr. Jerry W. Shay, Professor and Vice Chairman of Cell Biology at UT Southwestern, who led the team with his colleague, Dr. Woodring E. Wright, Professor of Cell Biology and Internal Medicine. Telomeres cap the ends of the cell's chromosomes to protect them from damage. But the telomeres become shorter every time the cell divides. Once they shorten to a critical length, the cell can no longer divide and enters into a senescent or growth-arrest phase in which the cell produces different products compared to a young quiescent cell. Most research in this area has focused on the role that the process plays in cancer, but telomere shortening also has been shown to influence which genes are active or silent. Dr. Shay and Dr. Wright found that even before the telomeres shorten to the critical length that damages the DNA, the slow erosion in length has an effect on the cell's regulation of genes that potentially contributes to aging and the onset of disease.
Scientists at The University of Manchester have identified an important new factor behind one of the major causes of blindness, which they hope could lead to new treatments. Age-related macular degeneration (AMD) is the major cause of blindness in the western world, affecting approximately 50 million people. It has been shown that sufferers are genetically predisposed to develop the condition. One of the most important risk-associated genes is called complement factor H (CFH). This encodes a protein called factor H (FH) that is responsible for protecting our eyes from attack by part of our immune system, called the complement system. FH achieves this protection by sticking to tissues, and when it is present in sufficient quantities it prevents the complement system from causing any damage. Scientists from Manchester’s Faculty of Medical and Human Sciences have now discovered that the protein factor H is not the main regulator of immunity in the back of the eye, instead it is a different protein that is made from the same CFH gene. This is called factor H-like protein 1 (FHL-1). The research was published online on October 15, 2014 in the Journal of Immunology. Dr. Simon Clark, a Medical Research Council Career Development Fellow, led the research: “FHL-1 is a smaller version of FH, in fact it is about a third of the size. However, it has all the necessary components to regulate the immune system and is still subject to the genetic alterations that affect AMD risk.