News Article | May 26, 2017
Obesity, already a global epidemic, is on the rise. Over one third of the U.S. population is currently afflicted, according to the Centers for Disease Control and the monetary costs alone are approaching $150 billion dollars annually. Causes of the epidemic include changing diets and greater sedentism, though environmental factors may also contribute. A new study compares the two most common surgical therapies for obesity, known as Roux-en-Y gastric bypass (RYGB), and laparoscopic adjustable gastric banding (LAGB). The results demonstrate that RYGB--the more aggressive of the two surgeries-- produces profound changes in the composition of microbial communities in the gut, with the resulting gut flora distinct from both obese and normal weight patients. The results are likely due to the dramatic reorganization of the gut caused by RYGB surgery, which increases microbial diversity. The new research paves the way for new diagnostics and therapies for obesity. The gamut of adverse health effects associated with obesity is broad, including such devastating illnesses as type 2 diabetes, coronary artery disease, stroke and certain forms of cancer. Patients often suffer loss of mobility, social isolation and inability to work. Currently bariatric surgery is the most effective treatment for morbid obesity, in terms of significant and sustained weight loss. In the new study, appearing in the current issue of the Nature Publishing Group journal International Society for Microbial Ecology (ISME), Zehra Esra Ilhan, Rosa Krajmalnik Brown and their colleagues at the Biodesign Institute at ASU, along with researchers from Mayo Clinic, and Pacific Northwest National Laboratory, explore microbial communities in the human gut following RYBG and LAGB surgeries. The results confirmed their earlier research with a smaller sample size, showing that in the case of the more aggressive and irreversible RYGB surgery, microbial communities underwent a profound and permanent shift following weight loss. The resulting post-surgical composition of gut microbes observed for RYGB patients was distinct from both normal weight and obese patients, and displayed the high microbial diversity associated with a healthy gut. The current study also applied the technique of nuclear magnetic resonance (NMR) to examine the metabolome--a composite of the metabolites produced by the various microbes in the gut, again noting significant alterations as a result of the RYGB procedure. In the case of the alternate treatment, LAGB, changes in the gut microbiota were mild and accompanying weight loss was less pronounced. "This is one of the first studies to show that anatomically different surgeries with different success rates have different microbiome and microbiome-related outcomes," notes Ilhan, lead author of the new paper. Further, the results indicate that correction of obesity tends to improve related metabolic conditions, including diabetes and high cholesterol. "One of the key findings of the paper confirms what we had already observed in earlier research. RYGP gastric bypass had a huge effect on the microbial community structure," Krajmalnik-Brown says. This fact may have profound implications for both the understanding and management of obesity. The millions of bacterial microbes in the human gut perform a vast range of critical functions in the body and have even been implicated in mood and behavior. Among their critical responsibilities are the micro-management of nutrients in the food we digest, hence their central place in the regulation of body weight. A tell-tale indicator of pathology in obese patients has been found in the gut, where a markedly lower diversity of microbial communities is observed. As Krajmalnik-Brown explains, diversity of gut microbes is essential to good health. "Diversity is good because of what we call functional redundancy," she says. "If you have 10 workers that can do the same job, when one of them gets sick, the job still gets done." Low microbial diversity in the gut, by contrast, is associated not only with obesity but a range of ailments including inflammatory bowel disease, ulcerative colitis and autism. (Earlier research by Krajmalnik-Brown and her colleagues demonstrated diminished diversity in the gut microbiome of autistic children and in a more recent study, improvement in the symptoms of autism was demonstrated following transplantation of beneficial microbes.) Competition in diverse microbial networks in the gut helps provide a system of checks and balances. Should diversity fall, a delicate democracy can be shattered and tyranny may prevail, as populations of microbes like Salmonella or Clostridium difficile--usually subsisting at low levels in the gut --expand and take over. The study sought to explore long-term changes in the gut in patients who had undergone either of the two surgeries at least 9 months prior, comparing them with normal weight and pre-bariatric obese patients. While the reasons for the sharp disparity of results between RYGB and gastric banding are not entirely clear, the results indicate that simply reducing the size of the stomach through gastric banding is not sufficient to induce the large changes in microbial communities observed for the RYGB group. One hypothesis the authors put forward is that RYGB alters the physiology of the gut to such a degree that microbes formerly unable to survive conditions in the obese gut are able to flourish in their surgically-modified surroundings. "One of the things we observe from the literature is that the oral microbiome community composition is very similar to the colon microbiome composition after bariatric surgery," Ilhan says. "You're giving new microbes a chance to make it. Most of the species are acid sensitive, which supports the idea that changes in stomach pH levels may permit these microbes to survive and make it to the colon." According to John DiBaise, a gastroenterologist at Mayo Clinic, Scottsdale and co-author of the new study, "These new data on microbial community structure and function significantly expand our knowledge on how the microbiome is associated with weight loss following bariatric surgery." While it seems clear that RYGB surgery produced permanent changes in bacterial communities in the gut, the resulting microbial community may also act to help maintain weight loss over the long term. Experiments have shown that transplantation of beneficial microbes from mice that have undergone RYGB surgery into obese mice induces dramatic weight loss. While these results have yet to be replicated in humans, the findings open the door to the eventual use of healthy microbial communities to treat obesity. Although the RYGB surgery has been quite successful for many patients suffering from morbid obesity, it is a serious, invasive procedure that is not without risks. Further, some patients are not successful and regain the weight they have lost post-surgery, perhaps because they lack the favorable microbes necessary for permanent weight loss. As Ilhan says, "a probiotic that would replace surgery would be great. Another positive outcome would be if we can find a microbial biomarker that will identify the best candidates for surgery and sustained weight loss." Research reported in this 24 publication was supported by the National Institute of Diabetes and Digestive and Kidney 25 Diseases of the National Institutes of Health under Award Number R01DK090379. Distinctive microbiomes and metabolites linked with weight loss after gastric bypass, but not gastric banding Zehra Esra Ilhan1,2, John K DiBaise3, Nancy G. Isern4, David W. Hoyt4, Andrew K 5 Marcus1, Dae-Wook Kang1, Michael D. Crowell3, Bruce E Rittmann1, and Rosa Krajmalnik-Brown1 1Swette Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, 85287, U.S.A., 2 School of Life Sciences, Arizona State University, 85287, U.S.A, 3 Mayo Clinic, Division of Gastroenterology, Scottsdale, U.S.A., 4 Environmental and Molecular Science Laboratory, Pacific Northwest National Laboratory, Richland, 12 WA, U.S.A.
News Article | April 27, 2017
Researchers have developed a personalized algorithm that predicts the impact of particular foods on an individual's blood sugar levels, according to a new study published in PLOS Computational Biology. The algorithm has been integrated into an app, Glucoracle, which will allow individuals with type 2 diabetes to keep a tighter rein on their glucose levels -- the key to preventing or controlling the major complications of a disease that affects 8 percent of Americans. Medications are often prescribed to help patients with type 2 diabetes manage their blood sugar levels, but exercise and diet also play an important role. "While we know the general effect of different types of food on blood glucose, the detailed effects can vary widely from one person to another and for the same person over time," said lead author David Albers, PhD, associate research scientist in Biomedical Informatics at Columbia University Medical Center (CUMC). "Even with expert guidance, it's difficult for people to understand the true impact of their dietary choices, particularly on a meal-to-meal basis. Our algorithm, integrated into an easy-to-use app, predicts the consequences of eating a specific meal before the food is eaten, allowing individuals to make better nutritional choices during mealtime." The algorithm uses a technique called data assimilation, in which a mathematical model of a person's response to glucose is regularly updated with observational data--blood sugar measurements and nutritional information--to improve the model's predictions, explained co-study leader George Hripcsak, MD, MS, the Vivian Beaumont Allen Professor and chair of Biomedical Informatics at CUMC. Data assimilation is used in a variety of applications, notably weather forecasting. "The data assimilator is continually updated with the user's food intake and blood glucose measurements, personalizing the model for that individual," said co-study leader Lena Mamykina, PhD, assistant professor of biomedical informatics at CUMC, whose team has designed and developed the Glucoracle app. Glucoracle allows the user to upload fingerstick blood measurements and a photo of a particular meal to the app, along with a rough estimate of the nutritional content of the meal. This estimate provides the user with an immediate prediction of post-meal blood sugar levels. The estimate and forecast are then adjusted for accuracy. The app begins generating predictions after it has been used for a week, allowing the data assimilator has learned how the user responds to different foods. The researchers initially tested the data assimilator on five individuals using the app, including three with type 2 diabetes and two without the disease. The app's predictions were compared with actual post-meal blood glucose measurements and with the predictions of certified diabetes educators. For the two non-diabetic individuals, the app's predictions were comparable to the actual glucose measurements. For the three subjects with diabetes, the apps forecasts were slightly less accurate, possibly due to fluctuations in the physiology of patients with diabetes or parameter error, but were still comparable to the predictions of the diabetes educators. "There's certainly room for improvement," said Dr. Albers. "This evaluation was designed to prove that it's possible, using routine self-monitoring data, to generate real-time glucose forecasts that people could use to make better nutritional choices. We have been able to make an aspect of diabetes self-management that has been nearly impossible for people with type 2 diabetes more manageable. Now our task is to make the data assimilation tool powering the app even better." Encouraged by these early results, the research team is preparing for a larger clinical trial. The researchers estimate that the app could be ready for widespread use within two years. This release is based on text provided by the authors. In your coverage please use this URL to provide access to the freely available article in PLOS Computational Biology: http://journals. Funding: GH, ML, and DJA are supported by a grant from the National Library of Medicine LM006910. LM, DJA and ML are supported by a grant from the Robert Wood Johnson Foundation RWJF 73070. LM is supported by a grant from the National Institute of Diabetes and Digestive Kidney diseases R01DK090372. Competing Interests: The authors have declared that no competing interests exist.
News Article | May 3, 2017
A new study shows that gene editing using CRISPR/Cas9 technology can work in rhesus monkey embryos. The results, published in the current issue of Human Molecular Genetics, open the door for pursuing gene editing in nonhuman primates as models for new therapies, including pharmacological, gene-, and stem cell-based therapies, says Keith Latham, animal science professor at Michigan State University and lead author of the study. “Our paper is the first in the US to publish on the use of this technology in nonhuman primate embryos,” he says. “Using nonhuman primate embryos is important because the closer we can approximate the human condition in the animal model, the better the chances of developing successful treatments as well as limiting risks that may be encountered in clinical trials.” While mice are mammals, they bear litters rather than individual offspring. Their anatomy and physiology differ in many respects from humans. While many advances in understanding diseases have been made first using mouse models, making the leap from a successful mouse study to clinical trials can be difficult or impossible for some areas of research. “If scientists want to test drugs for dementia, Alzheimer’s, or autism, ideal models would react similarly to humans in regards to the reduction of symptoms, outbreak of side effects, such as enduring the same lesions as humans do, or exhibiting similar behavioral characteristics,” says Latham. “Nonhuman primates are much better models for such diseases. And in terms of some surgical procedures, implants, developing prosthetics, or other therapies, nonhuman primates can prove better suited than rodents.” CRISPR has opened the door to do gene editing in many species other than mice. Developing this technology in nonhuman primates in the US would allow more scientists in this country to incorporate these models into their research, he adds. The advances will allow scientists to move forward and tackle some of the technical barriers related to the research. Other issues that may be later resolved are the commitment to increased costs and longer waiting times when using nonhuman primates. Fruit flies, often used in genetic studies, reproduce in two weeks. Rodents, with pre-disposed genetic characteristics, can be easily ordered and shipped to laboratories within days. Committing to raising nonhuman primates can cost around $15,000 and can take as long as four-to-six years to have a mature monkey with the desired genetic characteristics. The high-efficiency of gene editing that scientists are now able to achieve makes it worth the cost and the wait, Latham says. To conduct the research, Latham worked with the California National Primate Research Center, where the monkey embryos were produced, in collaboration with his co-investigator Catherine VandeVoort, an expert in nonhuman primate reproduction. Daniel Bauer, at Harvard Medical School, Boston Children’s Hospital, and Dana-Farber Cancer Institute also collaborated on the study. “Extreme amounts of care go into maintaining the well-being of the monkeys,” says Latham. “They follow strict protocols to ensure this is a priority. Funding came from the National Institutes of Health, Michigan State’s AgBioResearch, Michigan State, the National Institute of Diabetes and Digestive and Kidney Disease, the Burroughs Wellcome Fund, American Society of Hematology, Charles H. Hood Foundation, and Cooley’s Anemia Foundation.
News Article | May 1, 2017
EAST LANSING, Mich. - Mice have been and will continue to be good base models for human medicinal advances. However, their size and some of their physiological differences leave them lacking in important areas of human medicine, including neurological and reproductive research. In a study led by Michigan State University, scientists have shown that gene editing using CRISPR/Cas9 technology can be quite effective in rhesus monkey embryos ¬- the first time this has been demonstrated in the U.S. The results, published in the current issue of Human Molecular Genetics, open the door for pursuing gene editing in nonhuman primates as models for new therapies, including pharmacological, gene- and stem cell-based therapies, said Keith Latham, MSU animal science professor and lead author of the study. "Our paper is the first in the U.S. to publish on the use of this technology in nonhuman primate embryos," he said. "Using nonhuman primate embryos is important because the closer we can approximate the human condition in the animal model, the better the chances of developing successful treatments as well as limiting risks that may be encountered in clinical trials." While mice are mammals, they bear litters rather than individual offspring. Their anatomy and physiology differ in many respects from humans. While many advances in understanding diseases have been made first using mouse models, making the leap from a successful mouse study to clinical trials can be difficult or impossible for some areas of research. "If scientists want to test drugs for dementia, Alzheimer's or autism, ideal models would react similarly to humans in regards to the reduction of symptoms, outbreak of side effects, such as enduring the same lesions as humans do, or exhibiting similar behavioral characteristics," said Latham, who's with the College of Agriculture and Natural Resources and an MSU AgBioResearch scientist. "Nonhuman primates are much better models for such diseases. And in terms of some surgical procedures, implants, developing prosthetics, or other therapies, nonhuman primates can prove better suited than rodents." CRISPR has opened the door to do gene editing in many species other than mice. Developing this technology in nonhuman primates in the U.S. would allow more scientists in this country to incorporate these models into their research, he added. The advances will allow scientists to move forward and tackle some of the technical barriers related to the research. Other issues that may be later resolved are the commitment to increased costs and longer waiting times when using nonhuman primates. Fruit flies, often used in genetic studies, reproduce in two weeks. Rodents, with pre-disposed genetic characteristics, can be easily ordered and shipped to laboratories within days. Committing to raising nonhuman primates can cost around $15,000 and can take as long as 4-6 years to have a mature monkey with the desired genetic characteristics. The high-efficiency of gene editing that scientists are now able to achieve makes it worth the cost and the wait, Latham said. To conduct the research, Latham partnered with the California National Primate Research Center, where the monkey embryos were produced, in collaboration with his co-investigator Dr. Catherine VandeVoort, an expert in nonhuman primate reproduction. Dr. Daniel Bauer, at Harvard Medical School, Boston Children's Hospital and Dana-Farber Cancer Institute also collaborated on the study. The resources offered by the CNPRC were crucial for this work, Latham said. "Extreme amounts of care go into maintaining the well-being of the monkeys," he said. "They follow strict protocols to ensure this is a priority. So being able to conduct the science here at Michigan State while partnering with the center is the best combination of science and animal welfare." Additional MSU scientists contributing to the study include Uros Midic, Kailey Vincent and Benjamin Goheen. This research was funded by the National Institutes of Health, MSU AgBioResearch, MSU, the National Institute of Diabetes and Digestive and Kidney Disease, the Burroughs Wellcome Fund, American Society of Hematology, Charles H. Hood Foundation and Cooley's Anemia Foundation. Michigan State University has been working to advance the common good in uncommon ways for more than 150 years. One of the top research universities in the world, MSU focuses its vast resources on creating solutions to some of the world's most pressing challenges, while providing life-changing opportunities to a diverse and inclusive academic community through more than 200 programs of study in 17 degree-granting colleges. For MSU news on the Web, go to MSUToday. Follow MSU News on Twitter at twitter.com/MSUnews.
News Article | February 28, 2017
COLUMBIA, Mo. (Feb. 28, 2017) -- Hepatocellular carcinoma is the most common form of liver cancer, but treatment options are limited and many patients are diagnosed in late stages when the disease can't be treated. Now, University of Missouri School of Medicine researchers have developed a new treatment that combines chemotherapy and immunotherapy to significantly slow tumor growth in mice. The researchers believe that with more research, the strategy could be translated to benefit patients with the disease. "The current drug approved by the U.S. Food and Drug Administration to treat hepatocellular carcinoma only increases the average survival of patients by about three months," said Kevin Staveley-O'Carroll, M.D., Ph.D., chair of the MU School of Medicine's Hugh E. Stephenson Jr., M.D., Department of Surgery and director of Ellis Fischel Cancer Center. "While any extension of life is valuable, our research team is developing a new therapeutic strategy that might extend and improve the quality of life for these patients." Immunotherapy boosts the body's natural defenses to fight off cancer. The therapy has been used to help treat several cancers, such as melanoma and lung cancer. However, little research exists on combining immunotherapy with chemotherapy. During the study, one group of mice was treated with the chemotherapy agent sunitinib and another group was treated with an immunotherapy antibody known as anti-PD-1. Over a period of four weeks, tumors in mice treated with sunitinib grew 25 times larger. Tumors in mice treated with immunotherapy grew at a slower rate and were 15 times larger. However, a third group of mice treated with a combination of chemotherapy and immunotherapy experienced even slower tumor growth at a size that was only 11 times larger. "Our results show that a combined chemo-immunotherapeutic approach can slow tumor growth in mice more effectively than either individual treatment," said Guangfu Li, Ph.D., D.V.M., assistant professor in the MU Department of Surgery. "This innovative combination promotes an anti-tumor immune response and better suppresses growth of the cancer. Our findings support the need for a clinical trial to test whether this could become a cost-effective treatment that could help improve the lives of patients with liver cancer." The study, "Successful Chemo-immunotherapy against Hepatocellular Cancer in a Novel Murine Model," was published in the January issue of the Journal of Hepatology. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health (1 R01 CA164335-01A1 and R01-CA-025000) and the National Institute of Diabetes and Digestive Kidney Diseases of the National Institutes of Health (R01DK 057830). The researchers have no conflicts of interest to declare related to this study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
News Article | February 15, 2017
A $6.1 million, five-year grant from the National Institute of Diabetes, Digestive and Kidney Diseases at the National Institutes of Health may help researchers leverage massive amounts of genomic data to develop medical treatments and pharmaceuticals, according to an international team of researchers. The project -- called VISION or Validated Systematic Integration of Hematopoietic Epigenomes -- will integrate and functionally validate large amounts of emerging genomic and epigenetic data, according to Ross Hardison, T. Ming Chu Professor of Biochemistry and Molecular Biology, Penn State and a member of the Genome Sciences Institute of the Huck Institutes of the Life Sciences. Hardison, who will lead the international multidisciplinary team, added that the group will try to develop new tools for using data to facilitate advances both in basic research as well as medical applications, such as precision medicine. The project will focus on blood cell development as a model system for gene regulation in mammals. Blood cell development is vitally important to health because humans must continually replace old and damaged cells, and because many diseases, like leukemias and anemias, result from mis-regulation of gene expression during blood formation. "We are excited about this project because the methods we are developing can be applied not only to diseases that affect blood, but others as well," Hardison said. "A person's genetic profile can have a significant impact on disease susceptibility and response to specific treatments. However, the critical genetic variants that make up that genetic profile most often do not code for protein, but rather they are located in the much larger noncoding genome. We are studying these noncoding regions and finding new ways to extract valuable information about functional elements within them, which in turn informs us about how genetic variants play a role in disease." The results of the VISION project are being provided to the research community in readily accessible, web-based platforms and online tools that will allow researchers to extract meaningful, experimentally validated interpretations from the data and produce a guide for investigators to translate insights from mouse models to human clinical studies. Hardison is working with Cheryl Keller, project manager, Yu Zhang, associate professor of statistics, and Feng Yue, assistant professor of biochemistry and molecular biology, College of Medicine, all at Penn State; Mitchell Weiss, chair of the department of hematology, St. Jude Children's Research Hospital; Gerd Blobel, Professor of Pediactrics, University of Pennsylvania abd Children's Hospital of Philadelphia; James Taylor, associate professor of biology and associate professor of computer science, Johns Hopkins University; David Bodine, chief and senior investigator, National Human Genome Research Institute, NIH; Berthold Göttgens, principal investigator and professor of haematology, Cambridge Stem Cell Institute, University of Cambridge; Douglas Higgs, group head and principal investigator, and Jim Hughes, associate professor of genome biology, both of the Weatherall Institute of Molecular Medicine, Oxford University.
News Article | February 16, 2017
DUBLIN--(BUSINESS WIRE)--Research and Markets has announced the addition of the "Global Endoscopy Devices Market (2016-2022)" report to their offering. Endoscopy is the close examination of internal organs and vessels of the human body, which is used to inspect a person's digestive tract. It helps to suspect if an organ or precise area of the body is damaged, infected or cancerous. There are many types of endoscopic devices for detecting different types of diseases. One such device is Gastrointestinal Endoscopic Devices, used to inspect any infection or abnormalities in the function of the gastrointestinal tract. Other devices include endoscopes, visualization systems and operative devices. Factors affecting the growth of the market are the rise in the digestive and gastric diseases, affordable endoscopy device, and advancement in endoscopy technology. According to National Institute of Diabetes & Digestive and Kidney Diseases, 60 to 70 million people are affected by different digestive diseases. Based on region, Endoscopy Devices market is segmented into North America (US, Canada, Mexico and Rest of North America), Europe (Germany, UK, France, Russia, Spain, Italy and Rest of Europe), Asia-Pacific (China, Japan, India, South Korea, Singapore, Malaysia and Rest of Asia-Pacific) and Latin America, and Middle East & Africa. North America remained the dominant region in the global Endoscopy Devices market in 2015. Asia-Pacific would witness promising CAGR during the forecast period (2016-2022). For more information about this report visit http://www.researchandmarkets.com/research/vkg7xz/global_endoscopy.
News Article | December 2, 2016
ANN ARBOR, Mich. - According to an annual data report from the United States Renal Data System (USRDS), hospitalization and mortality rates for patients with chronic kidney disease continue to decline in the U.S. Along with those rates, the report highlights several current trends in kidney disease in the U.S., including Medicare spending in the patient population and number of kidney transplants. This year's report provides data from 2014 and is released by the USRDS coordinating center based at the University of Michigan Kidney Epidemiology and Cost Center, in partnership with Arbor Research Collaborative for Health. The report states that hospitalization rates among end-stage kidney disease patients decreased to 1.7 admissions per patient per year, as compared to 2.1 in 2005, or a reduction of 19 percent. End-stage kidney disease is the last stage of chronic kidney disease when the kidneys can no longer remove waste and excess water from the body, and dialysis or kidney transplantation is necessary for survival. In addition, mortality rates continue to decrease for dialysis and transplant patients, falling by 32 percent and 44 percent, respectively, since 1996. "Most recent estimates indicate 14.8 percent of U.S. adults have chronic kidney disease," says Rajiv Saran, M.D., professor of internal medicine at the University of Michigan and director of the USRDS coordinating center. "Fortunately, we've seen steeper declines in mortality rates in more recent years in this patient population, which is promising." "An interesting note on kidney transplants is a relatively recent initiative called kidney paired donation," Saran says. "The initiative is aimed at increasing the availability of living donor transplants, and in its simplest form is essentially when two living donors do not match with the respective recipients and decide to perform an exchange whereby the donation goes to each other's compatible recipient. Kidney paired donation transplants have risen sharply in recent years with 552 performed in 2014, representing 10 percent of living donor transplants that year." According to Saran, earlier diagnosis and treatment of chronic kidney disease can improve patient outcomes. "As newly reported cases of end-stage kidney disease continue to happen each year, physicians and patients need to have continued dialogue about the disease and how best to manage it," Saran says. "We hope this report provides fellow clinicians and researchers with valuable information they can use when discussing the disease with their patients and colleagues." Authors: In addition to Saran, the report's U-M authors include Bruce Robinson, M.D., Vahakn Shahinian, M.D., John Ayanian, M.D., Jennifer Bragg-Gresham, Ph.D., Debbie Gipson, M.D., Yun Han, M.S., Kevin He, Ph.D., William Herman, M.D., Michael Heung, M.D., Richard A. Hirth, Ph.D., David Hutton, Ph.D., Yi Li, Ph.D., Yee Lu, M.D., Hal Morgenstern, Ph.D., Brahmajee Nallamothu, M.D., Brett Plattner, M.D., Ronald Pisoni, Ph.D., Panduranga Rao, M.D., Douglas E. Schaubel, Ph.D., David T. Selewski, M.D., Peter Song, Ph.D., and Kenneth J. Woodside, M.D. Funding: Funding for the project came from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and the U.S. Department of Health and Human Services, under contract HHSN276201400001C, and the USRDS Coordinating Center Team, which consists of investigators and staff from the University of Michigan Health System, the Kidney Epidemiology and Cost Center, in partnership with Arbor Research Collaborative for Health. Disclosures: Dr. Hal Morgenstern is a consultant at Arbor Research Collaborative for Health. Dr. Jennifer Bragg-Gresham is a consultant with IMPAQ, and with Medical Education Institute (MEI) involving quality of life performance measures. Reference: United States Renal Data System. 2016 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Disease, Bethesda, MD, 2016. http://www. .
Gagniuc P.,University of Bucharest |
Ionescu-Tirgoviste C.,National Institute of Diabetes
BMC Genomics | Year: 2012
Background: The main function of gene promoters appears to be the integration of different gene products in their biological pathways in order to maintain homeostasis. Generally, promoters have been classified in two major classes, namely TATA and CpG. Nevertheless, many genes using the same combinatorial formation of transcription factors have different gene expression patterns. Accordingly, we tried to ask ourselves some fundamental questions: Why certain genes have an overall predisposition for higher gene expression levels than others? What causes such a predisposition? Is there a structural relationship of these sequences in different tissues? Is there a strong phylogenetic relationship between promoters of closely related species?Results: In order to gain valuable insights into different promoter regions, we obtained a series of image-based patterns which allowed us to identify 10 generic classes of promoters. A comprehensive analysis was undertaken for promoter sequences from Arabidopsis thaliana, Drosophila melanogaster, Homo sapiens and Oryza sativa, and a more extensive analysis of tissue-specific promoters in humans. We observed a clear preference for these species to use certain classes of promoters for specific biological processes. Moreover, in humans, we found that different tissues use distinct classes of promoters, reflecting an emerging promoter network. Depending on the tissue type, comparisons made between these classes of promoters reveal a complementarity between their patterns whereas some other classes of promoters have been observed to occur in competition. Furthermore, we also noticed the existence of some transitional states between these classes of promoters that may explain certain evolutionary mechanisms, which suggest a possible predisposition for specific levels of gene expression and perhaps for a different number of factors responsible for triggering gene expression. Our conclusions are based on comprehensive data from three different databases and a new computer model whose core is using Kappa index of coincidence.Conclusions: To fully understand the connections between gene promoters and gene expression, we analyzed thousands of promoter sequences using our Kappa Index of Coincidence method and a specialized Optical Character Recognition (OCR) neural network. Under our criteria, 10 classes of promoters were detected. In addition, the existence of " transitional" promoters suggests that there is an evolutionary weighted continuum between classes, depending perhaps upon changes in their gene products. © 2012 Gagniuc and Ionescu-Tirgoviste; licensee BioMed Central Ltd.
News Article | November 2, 2016
Baltimore, MD-- New work led by Carnegie's Steven Farber sheds light on how form follows function for intestinal cells responding to high-fat foods that are rich in cholesterol and triglycerides. Their findings are published in the Journal of Biological Chemistry. Enterocytes are specialized cells that line the insides of our intestines. The intestinal surface is like a toothbrush, with lots of grooves and protrusions that allow the cells there to grab and absorb nutrients from food as it is digested, including the lipid molecules from fatty foods. The cells absorb, process, and package these lipids for distribution throughout our bodies. Clearly they are very important for sustaining good health and keeping us alive, since lipids are necessary for many of the body's functions, including nutrient absorption and hormone production. "When we eat fatty foods, our body's response is coordinated between our digestive organs, our nervous system, and the microbes living in our gut," explained Farber. "Our research used zebrafish to focus on one aspect of this system--how the enterocyte cells inside our intestines respond to a high-fat meal." It turns out that fatty foods cause enterocyte cells to do some interior remodeling. Cells are like tiny factories, where different functions are carried out by highly specialized structures called organelles. In enterocytes, several of these organelles undergo changes in their shape in response to an influx of fats from rich foods. One such shape shift occurs in the nucleus, where the cell's DNA is stored. Farber's team demonstrated that the nucleus takes on a rapid and reversible ruffled appearance after fatty foods are consumed. This is of interest because a cell's genetic material is housed in the nucleus, and this is the location where different genes get turned on and off in response to external stimuli, such as the presence of lipids from fatty foods. So the team examined this issue further and found that the shape shifting in the nucleus coincides with the activation of certain genes that regulate the intestinal cell's ability to package and distribute the lipids to other parts of the body. The team was able to determine that this activation process occurs within an hour of eating high-fat foods. "Our working hypothesis is that the whole response to fat in the enterocyte--the remodeling and gene activation--may be coordinated by an organelle called the endoplasmic reticulum," said lead author Erin Zeituni. If the cell is a factory, then the endoplasmic reticulum it is the assembly line, where various cellular products are synthesized, stored, and packaged for distribution outside of the cell. It is constructed of a series of interconnected tube-like shapes. When the research team used pharmaceuticals to inhibit one function of the endoplasmic reticulum (the building of so-called lipoprotein particles that will export fats out of the cell), the gene activation process was inhibited for many key genes and nuclear ruffling was also altered. This demonstrated that the flux of fat in the endoplasmic reticulum is crucial for initiating the intestinal response to a fatty meal. "So much of the process by which enterocytes prepare and package fats for distribution to the circulatory and lymphatic system is poorly understood," Farber said. "These findings should help increase our understanding of the basic molecular and cellular biology of intestinal cells." This work was supported by the National Institute of Diabetes and Digestive and Kidney, National Institute of General Medicine, and the Zebrafish Functional Genomics Consortium. The Carnegie Institution for Science 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 has been a pioneering force in basic scientific research. Carnegie scientists are leaders in plant biology, developmental biology, astronomy, materials science, global ecology, and Earth and planetary science.