(Press-News.org) Sphingolipid metabolism contributes to diabetes-associated heart disease
Patients with type 2 diabetes are subject to a number of major health risks, including a greatly increased risk of heart failure. This is due in part to the development of diabetic cardiomyopathy (DbCM), a condition that significantly impairs heart function. In this issue of the Journal of Clinical Investigation, Ashley Cowart and colleagues at the Medical University of South Carolina report that an increase in specific types of saturated fatty acids (SFAs) and fatty acid metabolic pathways cause lipid overload and symptoms of DbCM in mice. Mice fed a diet high in SFAs developed alterations in the walls of the heart and heartbeat that are characteristic cardiomyopathy symptoms in humans. This study reveals the underlying metabolic mechanisms of DbCM and successfully models diabetes-associated heart disease in mice without genetic manipulation.
TITLE:
Ceramide Synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomycoytes
AUTHOR CONTACT:
L. Ashley Cowart
Medical University of South Carolina, Charleston, SC, USA
Phone: 843-437-3539; E-mail: cowartl@musc.edu
View this article at: http://www.jci.org/articles/view/63888?key=c24d3456fa8201bdc62a
Altered triglyceride metabolism in mice causes non-alcoholic fatty liver disease
Non-Alcoholic Fatty Liver Disease (NAFLD) is a condition in which triglycerides accumulate in liver cells. Individuals who develop NAFLD frequently have a mutation in a protein known as PNPLA3. In this issue of the Journal of Clinical Investigation, researchers led by Helen Hobbs at the University of Texas Southwestern Medical Center report on the contribution of this mutation to NAFLD in mice. Mice overexpressing mutant PNPLA3 did not metabolize triglycerides as well as normal mice indicating that mutation of PNPLA3 and the subsequent loss of appropriate triglyceride metabolism may underlie human NAFLD.
TITLE:
Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis
AUTHOR CONTACT:
Helen H. Hobbs
University of Texas Southwestern Medical Center, Dallas, TX, USA
Phone: 214 648 6724; Fax: 214 648 7539; E-mail: helen.hobbs@utsouthwestern.edu
View this article at: http://www.jci.org/articles/view/65179?key=96916004cc745c3dacf1
Researchers identify inflammatory mediators in pancreatic cancer
Pancreatic ductal adenocarcinoma is an aggressive cancer that feeds off inflammation in the tumor microenvironment. Current research is directed at determining how the tumor interacts with the surrounding tissue to drive inflammation and tumor growth. In this issue of the Journal of Clinical Investigation researchers led by George Miller at the New York University School of Medicine report that pancreatic cancer is driven by activation of a pro-inflammatory cell surface receptor known as TLR7. In a mouse model of pancreatic cancer, TLR7 activation accelerated tumor progression and drove the activation of oncogenic pathways. TLR7-deficient mice or mice that had been treated with a drug to block TLR7 activation had lower levels of inflammation and did not develop pancreatic cancer. These findings suggest that therapeutics targeting TLR7 may be an effective treatment for human pancreatic cancer.
TITLE:
Toll-Like Receptor 7 regulates pancreatic carcinogenesis in mice and humans
AUTHOR CONTACT:
George Miller
New York University School of Medicine, New York, NY, USA
Phone: 201-446-3608; E-mail: george.miller@med.nyu.edu
View this article at: http://www.jci.org/articles/view/63606?key=140bcf86df56061e2bb9
Putting a 'HEX' on muscle regeneration
A complex genetic regulatory network mediates the regeneration of adult skeletal muscles. In this issue of the Journal of Clinical Investigation, researchers at the State University of New York Downstate Medical Center in Brooklyn report that HEXIM1, a protein that regulates gene transcription, is important for skeletal muscle regeneration in mice. M.A.Q. Saddiqui and colleagues found that HEXIM1 blocks gene expression that is required for muscle regeneration after injury. Mice with a 50% reduction in HEXIM1 exhibited greater muscle mass and function after injury compared to mice with a normal amount of the gene. These results indicate that HEXIM1 may be a therapeutic target in degenerative muscle diseases.
TITLE:
HEXIM1 controls satellite cell expansion to regulate skeletal muscle regeneration
AUTHOR CONTACT:
M.A.Q. Siddiqui
SUNY Downstate Medical Center, Brooklyn, NY, USA
Phone: 718-270-1014; E-mail: maq.siddiqui@downstate.edu
View this article at: http://www.jci.org/articles/view/62818?key=81f201478a6fa71c020f
Untangling the cause of congenital lung disease
Alveolar Capillary Dysplasia (ACD) is a rare, lethal congenital malformation of the small blood vessels surrounding the alveoli of the lungs. Newborns with this disease develop respiratory distress and pulmonary hypertension within minutes to hours after birth. In this issue of the Journal of Clinical Investigation researchers led by Parviz Minoo at the University of Southern California report that loss of the protein Pten causes an ACD-like disease in mice. Mice pups that did not express Pten in the lung could not oxygenate their blood supply and died shortly after birth. Analysis of the lung cells showed that these mice did not develop the cells required for formation of the blood vessels that mediate gas exchange. These studies demonstrate a role for Pten in the development of alveoli-associated capillaries and suggest that Pten-mutant mice could serve as a model of human ACD.
TITLE:
Mesodermal Pten inactivation leads to alveolar capillary dysplasia-like phenotype
AUTHOR CONTACT:
Parviz Minoo
University of Southern California, Los Angeles, CA, USA
Phone: 323-226-4340; Fax: 213-236-5049; E-mail: minoo@usc.edu
View this article at: http://www.jci.org/articles/view/61334?key=6dab548111403637315b
Seeing the light: researchers track oncogenesis in the liver bile ducts
Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver cancer originating in the bile ducts. Based on studies of tumor tissue, ICC was originally classified as a cancer of the cells that line the bile ducts, known as cholangiocytes; however, ICC frequently co-occurs in patients with chronic hepatitis C infections, suggesting that ICC originates in liver cells (hepatocytes). To determine how ICC begins, In this issue of the Journal of Clinical Investigation, researchers led by Atsushi Suzuki at Kyushu University in Japan studied ICC progression in a mouse with fluorescently labeled liver cells. They demonstrated that ICC can arise from hepatocytes and identified signaling pathways that were required for oncogenesis in this cell type. This study will help define the pathology of ICC and, eventually, the design of new and more effective therapies.
TITLE:
Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes
AUTHOR CONTACT:
Atsushi Suzuki
Medical Institute of Bioregulation, Kyushu University, Fukuoka, , JPN
Phone: +81-92-642-6793; E-mail: suzukicks@bioreg.kyushu-u.ac.jp
View this article at: http://www.jci.org/articles/view/63065?key=281f33976ea6d1bd57f6
ACCOMPANYING ARTICLE
TITLE:
Cholangiocarcinomas can originate from hepatocytes in mice
AUTHOR CONTACT:
Holger Willenbring
University of California San Francisco, San Francsico, CA, USA
Phone: 415 476 2417; Fax: ; E-mail: willenbringh@stemcell.ucsf.edu
View this article at: http://www.jci.org/articles/view/63212?key=dbae1e72b11c2671f0dd
In myelofibrosis, it's all about location
In myelofibrosis (MF), hematopoietic stem cells become malignant. As the HSCs begin to grow out of control, they produce immature blood cells and fibrous tissue that destroy the bone marrow. Because the blood cells made in the marrow are of poor quality, HSCs in other organs such as the liver and spleen begin making blood cells to compensate. HSC behavior is determined by intrinsic properties as well as their environment. In a study published in the Journal of Clinical Investigation, Ronald Hoffman and colleagues at the Mount Sinai School of Medicine used HSCs isolated from the spleens and peripheral blood (PB) of human MF patients to determine how location influences HSC behavior. By transplanting the MF patient HSCs into mice, Hoffman and colleagues found that splenic HSCs were able to generate red and white blood cells for a prolonged period of time and behaved similarly to the normal HSCs found in bone marrow. In contrast, HSCs isolated from PB were not able to produce the full complement of white blood cells. These results suggest that the environment in the spleen may lead to the production of a greater number of malignant blood cells and contribute to disease progression.
TITLE:
Spleens of myelofibrosis patients contain malignant hematopoietic stem cells
AUTHOR CONTACT:
Xiaoli Wang
Mount Sinai School of Medicine, New York, NY, USA
Phone: 2122412284; E-mail: xiaoli2004osaka@gmail.com
View this article at: http://www.jci.org/articles/view/64397?key=535290f9b80230c57e59
### END
JCI early table of contents for October 1, 2012
2012-10-01
ELSE PRESS RELEASES FROM THIS DATE:
Public health messages can influence infectious disease stigmas
2012-10-01
UNIVERSITY PARK, Pa. -- Crafting public health messages about a disease may create stigmas that influence how likely people are to endorse certain interventions, such as isolating infected persons, forcing treatment on them and mapping their location, according to a Penn State researcher.
Rachel Smith, associate professor of communication arts and sciences and investigator with the University's Center for Infectious Disease Dynamics, used a hypothetical disease -- a virus carried by rodents -- to develop 16 different health alerts describing the virus and those who were ...
Preoperative needle breast biopsies can lead to improved treatment outcomes
2012-10-01
Chicago: Women suspected of having breast cancer now have more reasons to be diagnosed with a needle biopsy instead of a traditional open surgical biopsy. Besides avoiding the risks and discomfort of an open surgical procedure, needle biopsies can also lead to improved treatment outcomes according to findings from a new study published in the October issue of the Journal of the American College of Surgeons.
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Researchers identify a Dance Dance Revolution in kids' physical activity
2012-10-01
A study published in Pediatrics this morning by researchers at the University of Montreal offers positive news for Wii-loving teenagers and their parents: games such as Wii Sports and Dance Dance Revolution can bring them closer to recommended physical activity levels. The study is the first of its kind. "Teenage exergamers – people who play video games that require physical activity – are most likely females who are stressed about their weight. On average, they play two 50 minute sessions per week," said study author Jennifer O'Loughlin of the university's Department of ...
Nano-hillocks: Of mountains and craters
2012-10-01
In the field of nanotechnology, electrically-charged particles are frequently used as tools for surface modification. Researchers at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and the TU Vienna were at last able to reconcile important issues concerning the effects of highly charged ions on surfaces.
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Study reveals how memory load leaves us 'blind' to new visual information
2012-10-01
Trying to keep an image we've just seen in memory can leave us blind to things we are 'looking' at, according to the results of a new study supported by the Wellcome Trust.
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Physiological role of a novel hormone FNDC5/irisin revealed in humans
2012-10-01
Oxford, October 1, 2012 - A research team led by Dr. Christos Mantzoros, MD, PhD, at Beth Israel Deaconess Medical Center, Harvard Medical School, has published new findings elucidating the molecular and clinical role of FNDC5/irisin in humans.
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Computerized osteoporosis detection
2012-10-01
A computerized approach to examining patient bone X-rays for diagnosis of osteoporosis could side-step the subjectivity associated with visual examination, according to a new research paper in the International Journal of Biomedical Engineering and Technology published in October.
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The chemical memory of seawater
2012-10-01
Water does not forget, says Prof. Boris Koch, a chemist at the Alfred Wegener Institute for Polar and Marine Research in the Helmholtz Association. Irrespective of what happens in the sea: whether the sun shines, algae bloom or a school of dolphins swims through a marine area – everything and everyone leaves biomolecular tracks. With the help of a combination of new techniques, Boris Koch and colleagues can now identify and retrace some of these. In a special volume of the open access journal Biogeosciences, these scientists report on how these analyses work and which ...
First images of Landau levels revealed
2012-10-01
Physicists have directly imaged Landau Levels – the quantum levels that determine electron behaviour in a strong magnetic field – for the first time since they were theoretically conceived of by Nobel prize winner Lev Landau in 1930.
Using scanning tunnelling spectroscopy - a spatially resolved probe that interacts directly with the electrons - scientists at institutions including the University of Warwick and Tohoku University have revealed the internal ring-like structure of these Landau Levels at the surface of a semiconductor.
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UK-led project unravels the structures of membrane proteins
2012-10-01
The European Drug Initiative on Channels and Transporters (EDICT), which comes to an end this year, focused on membrane proteins. They make up a third of all proteins in every organism and play a key role in many human diseases.
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