(Press-News.org) PITTSBURGH, July 17, 2014 – Cystic fibrosis (CF) could be considered two diseases, one that affects multiple organs including the lungs, and one that doesn't affect the lungs at all, according to a multicenter team led by researchers at the University of Pittsburgh School of Medicine. The research, published online today in PLOS Genetics, showed that nine variants in the gene associated with cystic fibrosis can lead to pancreatitis, sinusitis and male infertility, but leave the lungs unharmed.
People with CF inherit from each parent a severely mutated copy of a gene called CFTR, which makes a protein that forms a channel for the movement of chloride molecules in and out of cells that produce sweat, mucus, tears, semen and digestive enzymes, said co-senior investigator David Whitcomb, M.D., Ph.D., chief of gastroenterology, hepatology and nutrition, Pitt School of Medicine. Without functional CFTR channels, secretions become thick and sticky, causing problems such as the chronic lung congestion associated with CF.
"There are other kinds of mutations of CFTR, but these were deemed to be harmless because they didn't cause lung problems," Dr. Whitcomb said. "We examined whether these variants could be related to disorders of the pancreas and other organs that use CFTR channels."
Co-senior author Min Goo Lee, M.D., Ph.D., of Yonsei University College of Medicine in Seoul, Korea, conducted careful tests of CFTR in pancreatic cell models and determined that a molecular switch inside the cell called WINK1 made CFTR channels secrete bicarbonate rather than chloride molecules.
"Pancreas cells use CFTR to secrete bicarbonate to neutralize gastric acids," Dr. Whitcomb said. "When that doesn't happen, the acids cause the inflammation, cyst formation and scarring of severe pancreatitis."
The research team found nine CFTR gene variants associated with pancreatitis after testing nearly 1,000 patients with the disease and a comparable number of healthy volunteers. They also learned that each variant could impair the WINK1 switch to prevent CFTR from becoming a bicarbonate-secreting channel.
Co-senior author Ivet Bahar, Ph.D., Distinguished Professor and John K. Vries Chair of Computational Biology, Pitt School of Medicine, built a computer model of the CFTR protein's structure and determined that all the nine variants alter the area that forms the bicarbonate transport channel, thus impairing secretion of the molecule.
"It turns out that CFTR-mediated bicarbonate transport is critical to thin mucus in the sinuses and for proper sperm function," Dr. Whitcomb said. "When we surveyed pancreatitis patients, there was a subset who said they had problems with chronic sinusitis. Of men over 30 who said they had tried to have children and were infertile, nearly all had one of these nine CFTR mutations."
He added that identification of the mechanisms that cause the conditions make it possible to develop treatments, as well as to launch trials to determine if medications that are used by CF patients might have some benefit for those who do not have lung disease, but who carry the other mutations.
INFORMATION:
The team includes researchers from the University of Pittsburgh, the Mayo Clinic, Brigham and Women's Hospital, and many other institutions that are part of the North American Pancreatitis Study Group.
The study was supported by National Institutes of Health grants DK061451, DK062420, GM086238, DK063922, CA047904 and RR024153; the Ministry for Health & Welfare, Republic of Korea; and Brain Korea 21 Project for Medical Sciences, Seoul.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu.
http://www.upmc.com/media
Contact: Anita Srikameswaran
Phone: 412-578-9193
E-mail: SrikamAV@upmc.edu
Contact: Courtney McCrimmon
Phone: 412-586-9773
E-mail: McCrimmonCP@upmc.edu
Pitt-led study suggests cystic fibrosis is 2 diseases, 1 doesn't affect lungs
2014-07-17
ELSE PRESS RELEASES FROM THIS DATE:
Scientists find protein-building enzymes have metamorphosed & evolved new functions
2014-07-17
LA JOLLA, CA AND JUPITER, FL—Scientists at The Scripps Research Institute (TSRI) and Hong Kong University of Science and Technology (HKUST) and their collaborators have found that ancient enzymes, known for their fundamental role in translating genetic information into proteins, evolved myriad other functions in humans. The surprising discovery highlights an intriguing oddity of protein evolution as well as a potentially valuable new class of therapeutic proteins and therapeutic targets.
"These new protein variants represent a previously unrecognized layer of biology—the ...
A new stable and cost-cutting type of perovskite solar cell
2014-07-17
Perovskite solar cells show tremendous promise in propelling solar power into the marketplace. The cells use a hole-transportation layer, which promotes the efficient movement of electrical current after exposure to sunlight. However, manufacturing the hole-transportation organic materials is very costly and lack long term stability. Publishing in Science, a team of scientists in China, led by Professor Hongwei Han in cooperation with Professor Michael Grätzel at EPFL, have developed a perovskite solar cell that does not use a hole-transporting layer, with 12.8% conversion ...
Scientists complete chromosome-based draft of the wheat genome
2014-07-17
MANHATTAN, Kansas — Several Kansas State University researchers were essential in helping scientists assemble a draft of a genetic blueprint of bread wheat, also known as common wheat. The food plant is grown on more than 531 million acres around the world and produces nearly 700 million tons of food each year.
The International Wheat Genome Sequencing Consortium, which also includes faculty at Kansas State University, recently published a chromosome-based draft sequence of wheat's genetic code, which is called a genome. "A chromosome-based draft sequence of the hexaploid ...
Ultrafast X-ray laser sheds new light on fundamental ultrafast dynamics
2014-07-17
MANHATTAN, Kansas — Ultrafast X-ray laser research led by Kansas State University has provided scientists with a snapshot of a fundamental molecular phenomenon. The finding sheds new light on microscopic electron motion in molecules.
Artem Rudenko, assistant professor of physics and a member of the university's James R. Macdonald Laboratory; Daniel Rolles, currently a junior research group leader at Deutsches Elektronen-Synchrotron in Hamburg, Germany, who will be joining the university's physics department in January 2015; and an international group of collaborators ...
No evidence that California cellphone ban decreased accidents, says Colarado University Boulder researcher
2014-07-17
In a recent study, a researcher at the University of Colorado Boulder found no evidence that a California ban on using hand-held cellphones while driving decreased the number of traffic accidents in the state in the first six months following the ban.
The findings, published in the journal Transportation Research Part A: Policy and Practice, are surprising given prior research that suggests driving while using a cellphone is risky. For example, past laboratory studies have shown that people who talk on a cellphone while using driving simulators are as impaired as people ...
Peering into giant planets from in and out of this world
2014-07-17
Lawrence Livermore scientists for the first time have experimentally re-created the conditions that exist deep inside giant planets, such as Jupiter, Uranus and many of the planets recently discovered outside our solar system.
Researchers can now re-create and accurately measure material properties that control how these planets evolve over time, information essential for understanding how these massive objects form. This study focused on carbon, the fourth most abundant element in the cosmos (after hydrogen, helium and oxygen), which has an important role in many types ...
Help wanted: Principals who love change
2014-07-17
DALLAS (SMU) – Training principals for new roles is key to U.S. Department of Education school reforms, according to a new report by SMU researchers. But insufficient training and support for principals to meet the new expectations is leading to a leadership crisis. Twenty percent of newly minted principals leave the profession after two years and seasoned professionals are opting for early retirement.
Education researchers Lee Alvoid and Watt Lesley Black Jr. examine school districts at the forefront of supporting and training effective principals in their report "The ...
CNIO researchers discover a gene that links stem cells, aging and cancer
2014-07-17
An organism is healthy thanks to a good maintenance system: the normal functioning of organs and environmental exposure cause damage to tissues, which need to be continuously repaired. This process is not yet well understood, but it is known that stem cells in the organs play a key role, and that when repair fails, the organism ages more quickly. Researchers from the Spanish National Cancer Research Centre (CNIO) have "discovered one of the key genes that make up the maintenance mechanism for tissues" says Miguel Foronda, the first author of the manuscript.
The study ...
First ab initio method for characterizing hot carriers
2014-07-17
One of the major road blocks to the design and development of new, more efficient solar cells may have been cleared. Researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) have developed the first ab initio method – meaning a theoretical model free of adjustable or empirical parameters – for characterizing the properties of "hot carriers" in semiconductors. Hot carriers are electrical charge carriers - electrons and holes – with significantly higher energy than charge carriers at thermal equilibrium.
"Hot carrier thermalization is a major source of ...
Untangling spider's webs
2014-07-17
For decades, the story of spider evolution went like this: As insects became more and more diverse, with some species taking to the skies, spiders evolved new hunting strategies, including the ability to weave orb-shaped webs to trap their prey.
From that single origin, the story goes, orb-weaver spiders diverged along different evolutionary paths, leading to today, where several species weave similar – though not identical – webs.
It's a good story, but there's just one problem – Harvard scientists now know it's not true.
The largest-ever phylogenetic study of ...