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News Article | April 13, 2017
Site: www.chromatographytechniques.com

When caught early, urinary tract infections are easy to treat. However, when left unchecked they can lead to complications such as kidney problems. Particularly vulnerable groups are those that can’t recognize symptoms or know to check for an infection, such as infant and geriatric populations. Researchers from Purdue University have now developed a bandage-sized autonomous sensor that can detect a urinary tract infection quickly and monitors frequently. Women have at least a 40 to 60 percent risk of contracting a urinary tract infection in their lifetime, and it is the second most common infection overall, according to the National Institute of Diabetes and Digestive and Kidney Diseases. The new technology relies on a disposable senor module that includes a battery that is triggered by urine and can be embedded in a diaper. When the battery is activated by urine it powers the sensor which detects nitrites and chemical compounds commonly linked to urinary tract infections.  The results are then wirelessly transmitted to a smartphone app, where the information is logged and sent to either the patient, caregiver or healthcare provider if needed. This is the only fully autonomous system that has been developed, making it unique from other similar technologies that are currently patented, according to the researchers. There are also benefits compared to existing detection methods. “Current testing relies on time-consuming and costly  urine culture tests performed at medical facilities and on at-home testing using store-purchased dipsticks that generally have high false alarm rates,” Babak Ziaie, professor of electrical and computer engineering at Purdue, said in a prepared statement. “Additionally, collecting urine samples for these methods can be challenging for infants and geriatric patients who suffer from neurodegenerative diseases. There’s also a privacy and dignity issue.” So far only synthetic urine samples have been tested on a prototype, but the researchers say the sensor has proved to be more accurate than dipsticks. In addition to early detection, the sensor can monitor on a regular basis, so it can transmit information about any changes in the status of a UTI over time. A pilot study is in the works and efforts are now focused on various aspects related to commercialization, such as sizing, methods to embed the sensor in diapers, and details involving the smartphone app.


News Article | April 18, 2017
Site: www.eurekalert.org

A study published in the Journal of Pediatrics suggests that children born with lower or higher weight than normal may be at increased risk for developing nonalcoholic fatty liver disease (NAFLD). These children also were at higher risk for more severe disease, but in different ways. Advanced scarring of the liver was associated with low birth weight, while more inflammation was linked to high birth weight. The study is the first to characterize the relationship between high birth weight and NAFLD. "With the obesity epidemic, we are seeing more babies with high birth weight than ever before," said co-author Mark Fishbein, MD, from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago. "Our study shows that these kids are more likely to have serious liver damage by the time they are teenagers." NAFLD affects up to 25 percent of the U.S. population, according to the American Liver Foundation. It is the most common cause of chronic liver disease in children and typically is diagnosed in early adolescence. In its most severe form it can lead to liver failure and the need for liver transplantation. "Being able to identify at birth infants at risk for severe liver disease will help initiate earlier interventions," said Fishbein, who also is an Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "Maintaining a healthy weight is the main strategy for preventing NAFLD in children." The multicenter study included 538 children under 21 years of age who were enrolled in the database of the National Institute of Diabetes and Digestive and Kidney Diseases NASH Clinical Research Network. All participants were diagnosed with NAFLD. Birth weights were categorized as low (1500-2499 g), normal (2500-3999 g) or high (4000 g and above) and compared with the birth weight distribution in the general U.S. population. The severity of liver disease was assessed by birth weight category. The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Advancing Translational Sciences. Research at Ann & Robert H. Lurie Children's Hospital of Chicago is conducted through the Stanley Manne Children's Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children's is ranked as one of the nation's top children's hospitals in the U.S.News & World Report. It is the pediatric training ground for Northwestern University Feinberg School of Medicine. Last year, the hospital served more than 198,000 children from 50 states and 51 countries.


News Article | May 3, 2017
Site: www.medicalnewstoday.com

The study - by researchers from the University of California-San Diego (UCSD) and colleagues from Human Longevity, Inc. in San Diego and the J. Craig Venter Institute in La Jolla, both in California - is published in the journal Cell Metabolism. Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by a buildup of fat in the liver. According to the National Institute of Diabetes and Digestive and Kidney Diseases, it is "one of the most common causes of liver disease in the U.S." NAFLD is a different condition to alcoholic liver disease, in which the fat buildup is due to heavy alcohol use. In the new study - which involved 135 participants and establishes "proof of concept" - the researchers found that the stool-based test was able to predict advanced NAFLD with an accuracy of between 88 and 94 percent. First author Rohit Loomba, a professor of medicine and director of the NAFLD Research Center at UCSD, says that determining who has or is at risk for NAFLD is a "critical unmet medical need." Although there are dozens of new drugs in the pipeline, if it were possible to better diagnose the disease, then patients could be better selected for trials and "ultimately [we] will be better equipped to prevent and treat it," Prof. Loomba adds. There are two forms of NAFLD: simple fatty liver and nonalcoholic steatohepatitis (NASH). Simple fatty liver is a form of NAFLD in which there is fat in the liver but without inflammation or cell damage. This form does not usually lead to liver damage or complications. NASH is type of NAFLD where, in addition to fat buildup, the liver also shows signs of inflammation and liver cell damage. The inflammation can lead to scarring or fibrosis, and then to more severe cirrhosis, which alters the liver's fundamental biology. NASH can also progress to liver cancer. Nobody knows exactly what causes NAFLD, or why some of the people affected have simple fatty liver while others have NASH. Estimates suggest that around 20 percent of people with NAFLD have NASH. In the U.S., between 30 and 40 percent of adults are thought to have NAFLD, and approximately 3 to 12 percent have NASH. Being obese - and having conditions related to obesity, such as type 2 diabetes - raises the risk of developing NAFLD. Prof. Loomba and colleagues note that NAFLD is thought to affect up to 50 percent of obese people. In their study report, the researchers note how studies have shown that the makeup of a person's gut microbiome - the trillions of microbes that live in the gut together with their genetic material - may affect their risk for obesity. This set them wondering if there might also be a link between obesity-related liver disease and the gut microbiome. If this is true, then it may be possible to analyze the makeup of the gut microbiome from a person's stool sample and link that to their NAFLD status. To test this theory, the team first examined 86 patients with NAFLD diagnosed by biopsy - including 72 with mild or moderate disease and 14 with advanced disease. They sequenced the genes from the participants' stool samples - analyzing the presence, location, and relative abundance of various microbe species. This process identified 37 species of bacteria that differentiated advanced NAFLD from the mild or moderate stage with 93.6 percent accuracy. The researchers then validated the finding in a second group of 16 patients with advanced NAFLD and 33 healthy volunteers who acted as controls. This time, they found that by testing the relative abundance of nine species of bacteria - seven of which were in the 37 identified previously - they could differentiate the NAFLD patients from the controls with 88 percent accuracy. The researchers are keen to point out that so far, the test has only been trialed on a small number of patients in a highly specialized setting. Even if further studies validate it, a stool sample test for NAFLD is unlikely to be available for clinical use for at least 5 years. Learn how a protein discovery may offer a new treatment target for NAFLD.


Jacksonville, FL- Only 21 percent of adolescents with type 1 diabetes maintain the recommended A1C levels, According to the National Institute of Diabetes and Digestive and Kidney Diseases, often related to psychological and behavioral impediments. Researchers from Nemours Children's Health System have been awarded $1.8 million from the National Institutes of Health to develop and test a new Transdisciplinary Care Model, where an advanced practice nurse, psychologist, and dietitian will work together with the patient either in-person or through virtual, telemedicine visits to improve family management of diabetes. The principal investigator of the three-year project is Tim Wysocki, PhD, Co-Director of the Center for Health Care Delivery Science at Nemours in Jacksonville, FL. Endocrinologists Dr. Anthony Gannon from the Nemours/Alfred I. duPont Hospital for Children in Wilmington, DE, and Dr. Matthew Benson from Nemours Children's Hospital in Orlando, FL, will recruit patient participants for the trial. "The shortage of endocrinologists has been emphasized by the increase of diabetes, specifically type 1, among our youth," said Dr. Wysocki. "With the supply of new endocrinologists being outstripped, it won't be possible for diabetes patients to be seen by endocrinologists at every visit." The study, titled Transdisciplinary Versus Usual Care for Type 1 Diabetes in Adolescence, will focus on addressing adolescent struggles with management of the disease. The model will allow for healthcare force multiplication, while also addressing psychosocial barriers to self-care more effectively. There will be 150 patients participating in the trial at Nemours practices in the Delaware Valley and Florida. The Randomized Controlled Trial will compare effects of Usual Care with those of Trans-Disciplinary Care delivered in face-to-face clinic visits or via Telehealth on glycemic control, treatment adherence, healthcare use, T1D-related distress, quality of life, and treatment satisfaction. At the conclusion of the trial, substantial information will be available that could justify and inform a definitive future test of this model. It could also determine if Telehealth or face-to-face delivery of Trans-Disciplinary Care would be better justified for evaluation in a future trial. "Our team professionals managing this trial in Delaware and Florida were carefully selected due to their exceptional experience on this subject," said Wysocki. "We are looking forward to getting started." The study will be done in collaboration with Co-Investigators, Drs. Jessica Pierce and Matthew Benson (Nemours Children's Hospital in Orlando, FL), Drs. Jennifer Shroff Pendley, Julia Price and Anthony Gannon (Nemours/Alfred I. duPont Hospital for Children in Wilmington, DE), and Biostatistician, Dr. Andre Williams (Nemours Children's Specialty Care in Jacksonville, FL).


News Article | May 4, 2017
Site: www.eurekalert.org

Glaucoma, a leading cause of blindness worldwide, most often is diagnosed during a routine eye exam. Over time, elevated pressure inside the eye damages the optic nerve, leading to vision loss. Unfortunately, there's no way to accurately predict which patients might lose vision most rapidly. Now, studying mice, rats and fluid removed from the eyes of patients with glaucoma, researchers at Washington University School of Medicine in St. Louis have identified a marker of damage to cells in the eye that potentially could be used to monitor progression of the disease and the effectiveness of treatment. The findings are published online May 4 in the journal JCI Insight. "There hasn't been a reliable way to predict which patients with glaucoma have a high risk of rapid vision loss," said principal investigator Rajendra S. Apte, MD, PhD, the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences. "But we've identified a biomarker that seems to correlate with disease severity in patients, and what that marker is measuring is stress to the cells rather than cell death. Other glaucoma tests are measuring cell death, which is not reversible, but if we can identify when cells are under stress, then there's the potential to save those cells to preserve vision." Glaucoma is the second-leading cause of blindness in the world, affecting more than 60 million people. The disease often begins silently, with peripheral vision loss that occurs so gradually that it can go unnoticed. Over time, central vision becomes affected, which can mean substantial damage already has occurred before any aggressive therapy begins. Many patients start receiving treatment when their doctors discover they have elevated pressure in the eye. Those treatments, such as eye drops, are aimed at lowering pressure in the eye, but such therapies may not always protect ganglion cells in the retina, which are the cells destroyed in glaucoma, leading to vision loss. Apte, also a professor of developmental biology, of medicine and of neuroscience, said that all current treatments for glaucoma are aimed at lowering pressure in the eye to reduce ganglion cell loss and not necessarily at directly preserving ganglion cells. Glaucoma specialists attempt to track the vision loss caused by ganglion cell death with visual field testing. That's when a patient pushes a button when they see a blinking light. As vision is lost, patients see fewer lights blinking in the periphery of the visual field, but such testing is not always completely reliable, according to the paper's first author, Norimitsu Ban, MD, an ophthalmologist and a postdoctoral research associate in Apte's laboratory. Some older people don't do as well on the visual field test for reasons that may not be related to what's going on in their eyes, Ban explained. He said that finding a marker of cell damage in the eye would be a much more reliable way to track the progression of glaucoma. "We were lucky to be able to identify a gene and are very excited that the same gene seems to be a marker of stress to ganglion cells in the retinas of mice, rats and humans," Ban said. Studying mouse models of glaucoma, Ban, Apte and their colleagues identified a molecule in the eye called growth differentiation factor 15 (GDF15), noting that the levels of the molecule increased as the animals aged and developed optic nerve damage. When they repeated the experiments in rats, they replicated their results. Further, in patients undergoing eye surgery to treat glaucoma, cataracts and other issues, the researchers found that those with glaucoma also had elevated GDF15 in the fluid of their eyes. "That was exciting because comparing the fluid from patients without glaucoma to those with glaucoma, the GDF15 biomarker was significantly elevated in the glaucoma patients," Apte said. "We also found that higher levels of the molecule were associated with worse functional outcomes, so this biomarker seems to correlate with disease severity." Apte and Ban don't believe that the molecule causes cells in the retina to die; rather, that it is a marker of stress in retinal cells. "It seems to be a harbinger of future cell death rather than a molecule that's actually damaging the cells," Apte said. A potential limitation of this study is that the fluid samples were taken from the eyes of patients only once, so it was not possible to monitor levels of GDF15 over time. In future studies, it will be important to measure the biomarker at several time points to determine whether levels of the biomarker increase as the disease progresses, Apte said. He also would like to learn whether GDF15 levels eventually decline in those who have significant vision loss from glaucoma. In theory, Apte said, when most of the ganglion cells in the retina already have died, fewer cells would be under stress, and that could mean lower levels. "So we are interested in doing a prospective study and sampling fluid from the eye over several months or years to correlate glaucoma progression with levels of this marker," he said. "We'd also like to learn whether levels of GDF15 change after treatment, a particularly important question as we try to develop therapies that preserve vision more effectively in these patients." Ban N, Siegfried CJ, Lin JB, Shiu YB, Sein J, Pita-Thomas W, Sene A, Santeford A, Gordon M, Lamb R, Dong Z, Kelly SC, Cavalli V, Yoshino J, Apte RS. GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients. JCI Insight. May 4, 2017. This work was supported by the National Eye Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke and the National Institute of General Medical Sciences, of the National Institutes of Health (NIH), grant numbers R01 EY019287, UL1 KL2TR000450, P30 DK56341, P30 DK02057, DK104995, R01 EY021515, R01 DE0220000, R01 NS0824446, P30 EY02687, T32 GM007200, UL1 TR000448 and TL1 TR000449. Additional funding provided by the Schulak Family Gift Fund for Retinal Research, the Jeffrey Fort Innovation Fund, the Kuzma Family Gift Fund, the Central Society for Clinical and Translational Research, a Research to Prevent Blindness Scientist Award, the Washington University Institute of Clinical and Translational Sciences, the American Federation for Aging Research, the Vitreoretinal Surgery Foundation and an unrestricted grant from Research to Prevent Blindness Inc. Washington University's Office of Technology Management has filed intellectual property applications based on these studies in which the authors Rajendra S. Apte and Jun Yoshino are listed as inventors. Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


By using optogenetics to control neurons in the basal ganglia, researchers achieve effects that last longer than deep brain stimulation Researchers working in the lab of Carnegie Mellon University neuroscientist Aryn Gittis, have identified two groups of neurons that can be turned on and off to alleviate the movement-related symptoms of Parkinson's disease. The activation of these cells in the basal ganglia relieves symptoms for much longer than current therapies, like deep brain stimulation and pharmaceuticals. The study, completed in a mouse model of Parkinson's, used optogenetics to better understand the neural circuitry involved in Parkinson's disease, and could provide the basis for new experimental treatment protocols. The findings, published by researchers from Carnegie Mellon, the University of Pittsburgh and the joint CMU/Pitt Center for the Neural Basis of Cognition (CNBC) are available as an Advance Online Publication on Nature Neuroscience's website. Parkinson's disease is caused when the dopamine neurons that feed into the brain's basal ganglia die and cause the basal ganglia to stop working, preventing the body from initiating voluntary movement. The basal ganglia is the main clinical target for treating Parkinson's disease, but currently used therapies do not offer long-term solutions. "A major limitation of Parkinson's disease treatments is that they provide transient relief of symptoms. Symptoms can return rapidly if a drug dose is missed or if deep brain stimulation is discontinued," said Gittis, assistant professor of biological sciences in the Mellon College of Science and member of Carnegie Mellon's BrainHub neuroscience initiative and the CNBC. "There is no existing therapeutic strategy for long lasting relief of movement disorders associated with Parkinson's." To better understand how the neurons in the basal ganglia behave in Parkinson's, Gittis and colleagues looked at the inner circuitry of the basal ganglia. They chose to study one of the structures that makes up that region of the brain, a nucleus called the external globus pallidus (GPe). The GPe is known to contribute to suppressing motor pathways in the basal ganglia, but little is known about the individual types of neurons present in the GPe, their role in Parkinson's disease or their therapeutic potential. The research group used optogenetics, a technique that turns genetically tagged cells on and off with light. They targeted two cell types in a mouse model for Parkinson's disease: PV-GPe neurons and Lhx6-GPe neurons. They found that by elevating the activity of PV-GPe neurons over the activity of the Lhx6-GPe neurons, they were able to stop aberrant neuronal behavior in the basal ganglia and restore movement in the mouse model for at least four hours -- significantly longer than current treatments. While optogenetics is used only in animal models, Gittis said she believes their findings could create a new, more effective deep brain stimulation protocol. Co-authors of the study include: Kevin Mastro, University of Pittsburgh Center for Neuroscience; Kevin Zitelli and Amanda Willard, Carnegie Mellon Department of Biological Sciences and CNBC; and Kimberly Leblanc and Alexxai Kravitz, National Institute of Diabetes and Digestive and Kidney Diseases. The research was funded by the National Institutes of Health (NIH) (NS090745-01, NS093944-01, NS076524), the National Science Foundation (DMS 1516288), the Brain & Behavior Research Foundation (formerly NARSAD), the Parkinson's Disease Foundation and the NIH Intramural Research Program. The authors also acknowledge the support of Carnegie Mellon's Disruptive Health Technology Institute.


News Article | May 5, 2017
Site: www.futurity.org

A biomarker could be a way to monitor how fast glaucoma is progressing, as well as the effectiveness of treatment. “There hasn’t been a reliable way to predict which patients with glaucoma have a high risk of rapid vision loss,” says principal investigator Rajendra S. Apte, professor of ophthalmology and visual sciences at Washington University in St. Louis. “But we’ve identified a biomarker that seems to correlate with disease severity in patients, and what that marker is measuring is stress to the cells rather than cell death. Other glaucoma tests are measuring cell death, which is not reversible, but if we can identify when cells are under stress, then there’s the potential to save those cells to preserve vision.” Glaucoma is the second leading cause of blindness in the world, affecting more than 60 million people. The disease often begins silently, with peripheral vision loss that occurs so gradually that it can go unnoticed. Over time, central vision becomes affected, which can mean substantial damage already has occurred before any aggressive therapy begins. Many patients start receiving treatment when their doctors discover they have elevated pressure in the eye. Those treatments, such as eye drops, are aimed at lowering pressure in the eye, but such therapies may not always protect ganglion cells in the retina, which are the cells destroyed in glaucoma, leading to vision loss. All current treatments for glaucoma are aimed at lowering pressure in the eye to reduce ganglion cell loss and not necessarily at directly preserving ganglion cells, says Apte, who is also a professor of developmental biology, of medicine, and of neuroscience. Glaucoma specialists attempt to track vision loss caused by ganglion cell death with visual field testing where a patient pushes a button when they see a blinking light. As vision is lost, patients see fewer lights blinking in the periphery of the visual field, but such testing is not always completely reliable, says Norimitsu Ban, an ophthalmologist and postdoctoral research associate in Apte’s laboratory. Ban is first author of the study in JCI Insight. Some older people don’t do as well on the visual field test for reasons that may not be related to what’s going on in their eyes, Ban says, so finding a marker of cell damage in the eye would be a much more reliable way to track the progression of glaucoma. “We were lucky to be able to identify a gene and are very excited that the same gene seems to be a marker of stress to ganglion cells in the retinas of mice, rats and humans,” he says. Studying mouse models of glaucoma, the researchers identified a molecule in the eye called growth differentiation factor 15 (GDF15), noting that the levels of the molecule increased as the animals aged and developed optic nerve damage. When they repeated the experiments in rats, they replicated their results. Further, in patients undergoing eye surgery to treat glaucoma, cataracts, and other issues, the researchers found that those with glaucoma also had elevated GDF15 in the fluid of their eyes. “That was exciting because comparing the fluid from patients without glaucoma to those with glaucoma, the GDF15 biomarker was significantly elevated in the glaucoma patients,’ Apte says. “We also found that higher levels of the molecule were associated with worse functional outcomes, so this biomarker seems to correlate with disease severity.’ The researches don’t believe that the molecule causes cells in the retina to die; rather, it’s a marker of stress in retinal cells. “It seems to be a harbinger of future cell death rather than a molecule that’s actually damaging the cells,” Apte says. A potential limitation of the study is that the fluid samples were taken from the eyes of patients only once, so it was not possible to monitor levels of GDF15 over time. In future studies, it will be important to measure the biomarker at several time points to determine whether levels of the biomarker increase as the disease progresses. Apte would like to know whether GDF15 levels eventually decline in those who have significant vision loss from glaucoma. In theory, when most of the ganglion cells in the retina already have died, fewer cells would be under stress, and that could mean lower levels. “So we are interested in doing a prospective study and sampling fluid from the eye over several months or years to correlate glaucoma progression with levels of this marker”‘ he says. “We’d also like to learn whether levels of GDF15 change after treatment, a particularly important question as we try to develop therapies that preserve vision more effectively in these patients.” The National Eye Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the National Institute of General Medical Sciences, of the National Institutes of Health funded the work. The Schulak Family Gift Fund for Retinal Research, the Jeffrey Fort Innovation Fund, the Kuzma Family Gift Fund, the Central Society for Clinical and Translational Research, a Research to Prevent Blindness Physician Scientist Award, the Washington University Institute of Clinical and Translational Sciences, the American Federation for Aging Research, the Vitreoretinal Surgery Foundation and an unrestricted grant from Research to Prevent Blindness Inc. provided additional funding.


News Article | May 8, 2017
Site: www.eurekalert.org

AUGUSTA, Ga. (May 8, 2017) - A protein that typically helps keep cells organized and on task becomes a tumor suppressor in the face of liver cancer, scientists say. The protein Scrib, which is emerging as both a tumor suppressor and oncogene depending on the cancer type, appears in liver cancer to migrate out of the protective outer layer of the cell and into its inner workings. Once inside, its expression increases and it suppresses expression of three oncogenes known to support liver cancer. "We found for the first time in liver cancer that Scrib can translocate to the cell cytoplasm and to the nucleus when the cells become cancerous," said Dr. Satya Ande, molecular biologist at the Georgia Cancer Center and assistant professor in the Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Augusta University. "Basically Scrib functions as a tumor suppressor that tries to suppress the growth of these cells," said Ande, corresponding author of the study in the journal Oncotarget. The work is the first hard evidence that Scrib functions as a tumor suppressor in human and animal liver cancer. Scrib more typically resides in the cell membrane where it aids cell polarity, which basically means keeping the cell's components - including the membrane, nucleus and cytoplasm - organized and on task for whatever function the cell has. Ande's research team has shown that in liver cancer, some Scrib remains in the cell membrane, but some also moves first to the cytoplasm, a jelly-like area that helps protect the cell and contains proteins that help give it shape and structure, then to the nucleus, where genetic material is housed. Together the nucleus and cytoplasm essentially comprise the cell's innards. At least in liver cancer, when Scrib makes this move, the Georgia Cancer Center scientist found it works to suppress expression of the oncogenes Yap1, c-Myc and cyclin D1. While relocation and increased expression of Scrib alone did not eliminate tumors in their mouse model, the tumors were smaller. Higher Scrib levels suppressed human liver cancer cell growth in culture, while low levels enhanced liver tumor growth in animal models. The scientists did not find spontaneous liver cancer in mice that were Scrib-deficient, indicating the protein has no normal role in the liver. Interestingly, in some other cancer types, Scrib's movement and increased expression are signs it intends to support cancer. Next steps include learning more about how important location is in Scrib's role as a liver cancer suppressor. Ande would also like to generate a mouse in which they can selectively overexpress Scrib in liver cells only, induce liver cancer and see what happens. In terms of Scrib's therapeutic potential, selectively activating tumor suppressors is difficult, Ande notes, although it's possible that gene therapy could one day be used to increase Scrib expression in liver cancer cells as part of an overall strategy to combat the cancer. More immediately, the work improves understanding of how liver cancer develops. "We are just trying to understand what happens when there are liver tumors in the body," Ande said. Inside the cytoplasm, for example, Scrib can interact with other proteins, like growth-promoting genes or proteins, and try to suppress their function and cell growth, he said. Why Scrib leaves its usual home in the cell membrane, likely has to do with the numerous changes that occur whenever cells become cancerous, he said. Ande thinks Scrib is attracted out of the membrane by the rapid cell proliferation that is a hallmark of cancer, going first to the cytoplasm and then, as cancer progresses, to the nucleus. Most of the work was done in later stages of liver cancer, and they found increased Scrib expression in about 70 percent of the 30 human liver tumors they analyzed. In different cancers, Scrib appears to have widely divergent roles. As examples, low levels seem to delay the onset of lymphoma but low levels also are present in the face of cancers of the colon, prostate and breast, in which Scrib has moved to the cell cytoplasm this time apparently to promote cancer, at least in animal models. Liver cancer incidence is slowly trending upward, with obesity, alcohol-use and hepatitis infections as major risk factors, said Ande. It tends to occur later in life and more often in men. Scrib appears generally to be overexpressed in most cancers. Others have found a variety of different tasks Scrib aids, including cell proliferation and death as well as stem cell maintenance and migration. The research was supported by the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases.


Baltimore, MD--Studying how our bodies metabolize lipids such as fatty acids, triglycerides, and cholesterol can teach us about cardiovascular disease, diabetes, and other health problems, as well as reveal basic cellular functions. But the process of studying what happens to lipids after being consumed has been both technologically difficult and expensive to accomplish until now. New work from Carnegie's Steven Farber and his graduate student Vanessa Quinlivan debuts a method using fluorescent tagging to visualize and help measure lipids in real time as they are metabolized by living fish. Their work is published by the Journal of Lipid Research. "Lipids play a vital role in cellular function, because they form the membranes that surround each cell and many of the structures inside of it," Quinlivan said. "They are also part of the crucial makeup of hormones such as estrogen and testosterone, which transmit messages between cells." Unlike proteins, the recipes for different lipid-containing molecules are not precisely encoded by DNA sequences. A cell may receive a genetic signal to build a lipid for a certain cellular purpose, but the exact type may not be indicated with a high degree of specificity. Instead, lipid molecules are built from an array of building blocks whose combinations can change depending on the type of food we eat. However, lipid compositions vary between cells and cellular structures within the same organism, so diet isn't the only factor determining which lipids are manufactured. "Understanding the balancing act in what makes up our bodies' lipids--between availability based on what we're eating and genetic guidance--is very important to cell biologists," Farber explained. "There is growing evidence that these differences can affect wide arrays of cellular processes." For example, omega-3 fatty acids, which are lipid building blocks found in foods like salmon and walnuts, are known to be especially good for heart and liver health. There is evidence that when people eat omega-3 fatty acids, the cellular membranes into which they are incorporated are less likely to overreact to signals from the immune system than membranes comprised of other kinds of lipids. This has an anti-inflammatory effect that could prevent heart or liver disease. Farber and Quinlivan's method allowed them to delve into these kinds of connections. They were able to tag different kinds of lipids, feed them to live zebrafish, and then watch what the fish did with them. "If we fed the fish a specific type of fat, our technique allowed us to determine into what molecules these lipids were reassembled after they were broken down in the small intestine and in which organs and cells these molecules ended up," Farber explained. The tags they used were fluorescent. So Farber and Quinlivan and their team were actually able to see the fats that they fed their zebrafish glowing under the microscope as they were broken down and reassembled into new molecules in different organs. Further experiments allowed them to learn into what types of molecules the broken down fat components were incorporated. "Being able to do microscopy and biochemistry in the same experiment made it easier to understand the biological meaning of our results," Quinlivan said. "We hope our method will allow us to make further breakthroughs in lipid biochemistry going forward." The other members of the team were Carnegie's Meredith Wilson, and Josef Ruzicka of Thermo Fisher Scientific. This work was supported by the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of General Medicine grant of the Zebrafish Functional Genomics Consortium. The Carnegie Institution for Science (carnegiescience.edu) is a private, nonprofit organization headquartered in Washington, D.C., with six research departments throughout the U.S. Since its founding in 1902, the Carnegie Institution

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