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Archive - 2014

November 19th

Study Shifts Focus for Origin of Lou Gehrig’s Disease to Brain’s Motor Neurons

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.

November 18th

Marfan Drug Study Argues for Treatment at Younger Age and Earlier Stage of Disease; Suggests Losartan Equally Effective As Atenol

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.

November 14th

Treasure Trove of Blind Cave Beetles Discovered in Southern China

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.

Scientists Discover Telomere Mechanism That Controls Fitness of Cells, Impacting Aging and Disease

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.

New Insight into Age-Related Macular Degeneration

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.

DNA Sequencing Helps Identify Mitochondrial Genetic Defects in Glaucoma

Scientists from the University of Liverpool have sequenced the mitochondrial genome in glaucoma patients to help further understanding of the genetic basis for the disease. Glaucoma is a major cause of irreversible blindness, affecting more than 60 million people worldwide, predicted to increase to an estimated 79.6 million people by 2020. It is thought that the condition has genetic origins and many experiments have shown that new sequencing approaches could help understand how the condition develops. Studies on primary open-angle glaucoma - the most common form of glaucoma - have shown that mutations in mitochondria, the energy generating structures in all cells, could give valuable insight into how to prevent the disease. Using new gene sequencing techniques, called massively parallel sequencing, the Liverpool team has produced data on the mitochondrial genome taken from glaucoma patients from around the world. The impact that mitochondrial gene change has on disease progression has been difficult to fully determine as cells in the human body can contain mixtures of healthy and mutated mitochondrial genes. Using this new technology, however, the researchers aim to support the delivery of personalized medicines to identify drugs that will target mutated mitochondria. Professor Colin Willoughby, from the University's Institute of Ageing and Chronic Disease, explains: "Understanding the genetic basis of glaucoma can direct care by helping to determine the patient's clinical risk of disease progression and visual loss. Increasing evidence suggests that mitochondrial dysfunction results in glaucoma and drugs that target mitochondria may emerge as future therapeutic interventions.

November 13th

Beetle and Longtime Fungal Associate Go Rogue

Scientists with the U.S. Forest Service and Colorado State University examined a fungus native to North America, the native beetle that carries it, and their host tree and found something surprising: Geosmithia morbida (the fungus) and the walnut twig beetle co-evolved and, while the beetle/fungus complex was once the equivalent of a hang nail for a black walnut tree, it has now become lethal. Research published on November 13, 2014 in PLOS ONE by U.S. Forest Service scientist Dr. Keith Woeste, Colorado State University scientists Dr. Marcelo M. Zerillo and Dr. Jorge Ibarra Caballero, and colleagues, details the origins and spread of Thousand Cankers Disease (TCD), a fungal disease that is threatening the health of black walnut in the Eastern United States. The study provides a detailed look at the genetic diversity of the fungus and how that diversity is distributed on the landscape, allowing scientists to make much stronger conclusions about the sources of TCD spread in the past and in the future. "Black walnut is a species with tremendous economic and cultural significance," said Dr. Michael T. Rains, Director of the Northern Research Station and the Forest Products Laboratory. "To help ensure this species sustains it vibrancy, Forest Service scientists are working with state agencies, other federal agencies, and university partners to advance survey and detection efforts and to understand the genetics of the disease, as well as resistance to TCD." When black walnut trees in California and Arizona began dying of TCD two decades ago, some scientists believed that the walnut twig beetle (image) had acquired a new and probably non-native fungus that was killing the trees. "That wasn't the case," said Dr. Woeste, a research plant molecular geneticist with the U.S.

Common Cholesterol-Fighting Drug May Prevent Hysterectomies in Women with Uterine Fibroids

Researchers at the University of Texas Medical Branch (UTMB) at Galveston, in collaboration with scientists at The University of Texas Health Science Center at Houston (UTHealth), the Baylor College of Medicine, and the Georgia Regents University, report for the first time that the cholesterol-lowering drug simvastatin inhibits the growth of human uterine fibroid tumors. These new data were published online on October 30, 2014, and are scheduled to appear in the January print edition of the Journal of Biological Chemistry (JBC). Statins, such as simvastatin, are commonly prescribed to lower high cholesterol levels. Statins work by blocking an early step in cholesterol production. Beyond these well-known cholesterol-lowering abilities, statins also combat certain tumors. Statins have previously been shown to have anti-tumor effects on breast, ovarian, prostate, colon, leukemia, and lung cancers. The effect of statins on uterine fibroids was previously unknown. “Non-cancerous uterine fibroids are the most common type of tumor in the female reproductive system, accounting for half of the 600,000 hysterectomies done annually in the U.S. Their estimated annual cost is up to $34 billion in the U.S. alone,” said UTMB’s Dr. Mostafa Borahay, assistant professor in the department of obstetrics and gynecology and lead author of the JBC article. “Despite this, the exact cause of these tumors is not well understood, as there are several genetic, familial, and hormonal abnormalities linked with their development.” The current study investigated the impact of simvastatin on human uterine fibroid cell growth. The researchers revealed that simvastatin impedes the growth of uterine fibroid tumor cells. The researchers also studied the way simvastatin works to suppress these tumors.

Cold-Induced Pain Linked to the Garlic and Mustard Receptor

Some people experience cold not only as feeling cold, but actually as a painful sensation. This applies even to fairly mild temperatures - anything below 20°C. A group of researchers from Lund University in Sweden has now identified the mechanism in the body that creates this connection between cold and pain. It turns out that it is based on the same receptor (TRP subtype A1) that reacts to the pungent substances in mustard and garlic. This result was reported online on November 11, 2014 in PNAS. Professor of Pharmacology Peter Zygmunt and Professor of Clinical Pharmacology Edward Högestätt have long conducted research on pain and the connection between pain and irritant substances in mustard, garlic, and chilli. In large quantities, these strong spices can cause burning or irritant sensations in the mouth and throat, and can also cause rashes and swelling. When the eyes are exposed, these spices produce strong pain and lacrimation, a property that has been exploited in pepper spray and tear gas. The reason is that the substances affect nerves that are part of the pain system and that are activated by inflammation. Ten years ago, the Lund research group identified the receptor for mustard and garlic, i.e. the way in which the pungent substances in the spices irritate the nerve cells. Since then, the question of whether this receptor also responds to cold has been a matter of debate. However, the researchers have now demonstrated that this is the case. "We have worked with Professors of Biochemistry Urban Johanson and Per Kjellbom here in Lund to extract the human receptor protein and insert it into an artificial cell membrane. There we could see that it reacted to cold," explained Professor Zygmunt. The findings increase our knowledge of the human body's temperature senses.

HFE Gene Variant, Found in 30 percent of ALS Patients, Speeds Up Disease Progression

Mice bred to carry a gene variant found in a third of ALS patients have a faster disease progression and die sooner than mice with the standard genetic model of the disease, according to Penn State College of Medicine researchers. Understanding the molecular pathway of this accelerated model could lead to more successful drug trials for all ALS patients. Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a degeneration of lower and upper motor neurons in the brainstem, spinal cord, and the motor cortex. The disease, which affects 12,000 Americans, leads to loss of muscle control. People with ALS typically die of respiratory failure when the muscles that control breathing fail. Penn State researchers were the first to discover increased iron levels in the brains of some patients with the late-onset neurodegenerative disorders Parkinson's disease and Alzheimer's disease. A decade ago, they also identified a relationship between ALS and excess iron accumulation when they found that 30 percent of ALS patients in their clinic carried a variant of a gene known as HFE [high iron (Fe)] that is associated with iron overload. For this study, the researchers crossbred mice with the H63D HFE gene variant with the standard mice used in ALS research. "When we followed the disease progression and the behavior of our crossbred mice compared to the standard mice, we saw significant differences," said Dr. James Connor, vice chair of neurosurgery research and director of the Center for Aging and Neurodegenerative Diseases. The crossbred mice performed significantly worse on tests of forelimb and hindlimb grip strength and had a 4 percent shorter life span. The researchers published their findings in the December 2014 issue of the BBA Molecular Basis of Disease.