Certain Cancer Therapies' Success Depends on Presence of Immune Cell, Mouse Study Shows

The immune system may play a critical role in ensuring the success of certain types of cancer therapies, according to a new study by researchers at the Stanford University School of Medicine. The research showed treatments that disable cancer-promoting genes called oncogenes are much more successful in eradicating tumors in the presence of a signaling molecule secreted by kind of immune cell called a T helper cell.

The finding is important because many drugs now in use in humans are often tested in lab animals with weakened immune systems and many human cancer therapies actually compromise a patient's immune system.

"We may be biasing ourselves by expecting these drugs to work on their own, without factoring in the effect of the immune system," said Dean Felsher, MD, PhD, associate professor of medicine and of pathology and the leader of the Stanford Molecular Therapeutics Program. "We're looking for efficacy while ignoring a whole part of biology. What we're choosing as the best candidates may not in fact be the best drugs for patients."

Felsher, who is also a member of the Stanford Cancer Center, is the senior author of the research, which will be published online Oct. 28 in Cancer Cell.

Oncogenes are genes that, when mutated, contribute to the development of many cancers including leukemias and lymphomas. Although cancers are by nature quite complex, some types of tumors rely so completely on the activity of the mutated genes that researchers have coined the term "oncogene addiction." Blocking the effect of these oncogenes -- the focus of several current cancer therapies -- can cause the tumors to shrink. For instance, the drug imatinib, marketed as Gleevec, targets a key oncogene in chronic myelogenous leukemia and gastrointestinal stromal tumors.

"Researchers and clinicians know that blocking the activity of oncogenes can confer dramatic clinical benefit," said Felsher. "But until recently all of us had assumed that most of the effects we saw on the tumor were relatively independent of the microenvironment of the host."

In contrast, Felsher and his colleagues found that disabling an oncogene called Myc in mice with Myc-dependent leukemias caused complete regression of tumors only in mice with intact immune systems. Tumors in mice with completely or partially compromised immune systems shrank more slowly and were left with a thousand-fold more residual disease. These tumors were also significantly more likely to recur during the 80 days after treatment was stopped.

When the researchers investigated more closely, they found that it was the absence of a type of T cell called CD4 helper cells that was responsible for the differences in recurrence rates (28.5 percent of animals lacking CD4-positive cells had tumor recurrence vs. none in animals missing another type of T cell called a CD8-positive cell). After the researchers added CD4-positive cells to immunocompromised animals, the mice regained the ability to eliminate the tumor and none experienced tumor recurrence during the follow-up period.

Examining the tumor cells after Myc inactivation indicated that the differences in tumor regression and recurrence were not due to an inability of the immune-compromised animals to trigger tumor cell death (known as apoptosis) or to stop the cells from dividing. Rather, the cancer cells in the immunocompromised animals were less likely to slide into a state of inactivity called senescence and, unlike in the wild-type mice, continued to recruit new blood vessels to the tumor site (a process called angiogenesis).

"This was already provocative," said Felsher. "When the immune system was impaired, the treatment didn't work as well. But we then went a step further. We wanted to know specifically what it was about the CD4-positive cells that influenced tumor regression and recurrence."

They began by looking at signaling molecules secreted by immune cells. These molecules, called cytokines, relay instructions to other cells in the area to coordinate the body's response to infection or disease. Felsher and his colleagues found that the expression levels of many cytokines varied between the wild-type mice and those with compromised immune systems. One in particular, a molecule called thrombospondin-1, was especially interesting. It is produced by CD4-positive T cells, and it regulates angiogenesis.

"We knew that if we replaced CD4-positive cells in immune-compromised mice, we repaired their ability to reject the tumors when Myc was inactivated," said Felsher. "When we tried the same experiment with CD4 cells that couldn't express thrombospondin, the mice couldn't reject the tumor."

Therefore, the presence of thrombospondin is important to the process of tumor rejection caused by oncogene inactivation. Felsher and his colleagues saw a similar effect in a mouse model of another type of leukemia that is dependent on the expression of different oncogenes, suggesting that their findings may translate to other instances of oncogene addiction. They also showed that wild-type mice treated with an immune suppressor called cyclosporine A (commonly used in human organ transplant recipients to prevent rejection) had a similar effect on angiogenesis and the ability of the tumor cells to enter senescence.

"The problem is, many treatments for patients with lymphoma and leukemia attack both the cancer cells and the immune system," said Felsher. "So we really have to think about this. We can't assume that therapies that target oncogenes act independently of the rest of the body. They may depend on an intact immune system."

Although many patients believe that their immune systems are inherent cancer fighters, it's not always the case, said Felsher. Rather, most cancers occur and progress in the presence of the immune system, each shaping the other. Under some conditions the immune system can actually facilitate cancer progression, while in others it helps to dismantle established tumors.

"Think of the immune system as a contractor," said Felsher. "They come in and do what they're paid to do. In the presence of thrombospondin, and when oncogenes are inactivated, the immune system can help destroy the cancer. In other situations it facilitates the cancer's growth. So we have to think about this very carefully."

In addition to Felsher, other Stanford researchers involved in the study include graduate student Kavya Rakhra; former medical students Pavan Bachireddy, MD, and Andrew Kopelman, MD; postdoctoral scholar Tahera Zabuawala, PhD; former postdoctoral scholar Robert Zeiser, MD; research associate Liwen Xu, PhD; oncology instructor Alice Fan, MD; and research assistant Qiwei Yang.

The research was funded by the Burroughs Wellcome Fund, the Damon Runyon Foundation, the National Institutes of Health and the Leukemia and Lymphoma Society.

Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Journal Reference:

1. Kavya Rakhra, Pavan Bachireddy, Tahera Zabuawala, Robert Zeiser, Liwen Xu, Andrew Kopelman, Alice C. Fan, Qiwei Yang, Lior Braunstein, Erika Crosby, Sandra Ryeom, and Dean W. Felsher. CD4 T Cells Contribute to the Remodeling of the Microenvironment Required for Sustained Tumor Regression upon Oncogene Inactivation. Cancer Cell, 2010; DOI: 10.1016/j.ccr.2010.10.002

Courtesy: ScienceDaily

Risk Markers for Alzheimer’s Disease

Risk markers could play an important role in this. These are substances linked to Alzheimer's that are found in unusually high or unusually low quantities in patients who go on to develop the disease.

Associate Professor Oskar Hansson, linked to Lund University and Skåne University Hospital in Sweden, has identified two such risk markers. He has tested these on individuals who sought treatment at the hospital's memory clinic and who displayed 'mild cognitive impairment' -- poorer memory than normal for their age.

Of the 160 subjects tested, 33 per cent developed Alzheimer's disease within five years. Sixteen per cent developed other forms of dementia, while the remaining half stayed at the level of 'mild forgetfulness'. The risk markers made a quite clear distinction between those who would later suffer from Alzheimer's and those who were not at risk.

"The 'positive connection' was 71 per cent, which is not sufficient to definitely predict who will get the disease. The 'negative connection', on the other hand, was 94 per cent, which means that it is possible to predict who in all likelihood will not get the disease," says Oskar Hansson.

Those who do not have the risk markers are therefore not at high risk of developing Alzheimer's, despite having a poor memory. They can be given this reassuring news and do not have to return for regular Alzheimer's checks.

Individuals who do not have the risk markers can also be removed from all future clinical studies of new Alzheimer's drugs.

"The studies are simpler and more correct if they are done on the right patient group from the beginning, i.e. those who really are in the risk zone for Alzheimer's disease. It is also more ethical not to include patients who are not at risk. They have nothing to gain from the medication, but may have something to lose if the drug causes side-effects," says Oskar Hansson.

The biomarkers are extracted from spinal fluid through a needle inserted into the lower spine. This is not the same as a bone marrow test, which is a much more extensive and unpleasant procedure.

Incidence of Alzheimer's disease is increasing rapidly all over the world. In Sweden there are currently around 120 000 people with the disease, but the number is expected to increase in line with the aging population. Because patients require a lot of care, Alzheimer's and other forms of dementia are estimated to cost society as much as cardiovascular disease, cancer and stroke combined.

Journal Reference:

1. Joakim Hertze, Lennart Minthon, Henrik Zetterberg, Eugeen Vanmechelen, Kaj Blennow, Oskar Hansson. Evaluation of CSF Biomarkers as Predictors of Alzheimer's Disease: A Clinical Follow-Up Study of 4.7 Years. Journal of Alzheimer's Disease, 2010; 21 (4): 1119-1128 DOI: 10.3233/JAD-2010-100207

Courtesy: ScienceDaily

Plants Play Larger Role Than Thought in Cleaning Up Air Pollution, Research Shows

Vegetation plays an unexpectedly large role in cleansing the atmosphere, a new study finds.

The research, led by scientists at the National Center for Atmospheric Research (NCAR) in Boulder, Colo., uses observations, gene expression studies, and computer modeling to show that deciduous plants absorb about a third more of a common class of air-polluting chemicals than previously thought.

The new study, results of which are being published in Science Express, was conducted with co-authors from the University of Northern Colorado and the University of Arizona. It was supported in part by the National Science Foundation (NSF), NCAR's sponsor.

"Plants clean our air to a greater extent than we had realized," says NCAR scientist Thomas Karl, the lead author. "They actively consume certain types of air pollution."

The research team focused on a class of chemicals known as oxygenated volatile organic compounds (oVOCs), which can have long-term impacts on the environment and human health.

"The team has made significant progress in understanding the complex interactions between plants and the atmosphere," says Anne-Marie Schmoltner of NSF's Division of Atmospheric and Geospace Sciences, which funded the research.

The compounds form in abundance in the atmosphere from hydrocarbons and other chemicals that are emitted from both natural sources--including plants--and sources related to human activities, including vehicles and construction materials.

The compounds help shape atmospheric chemistry and influence climate.

Eventually, some oVOCs evolve into tiny airborne particles, known as aerosols, that have important effects on both clouds and human health.

By measuring oVOC levels in a number of ecosystems in the United States and other countries, the researchers determined that deciduous plants appear to be taking up the compounds at an unexpectedly fast rate--as much as four times more rapidly than previously thought.

The uptake was especially rapid in dense forests and most evident near the tops of forest canopies, which accounted for as much as 97 percent of the oVOC uptake that was observed.

Karl and his colleagues then tackled a follow-up question: How do plants absorb such large quantities of these chemicals?

The scientists moved their research into their laboratories and focused on poplar trees. The species offered a significant advantage in that its genome has been sequenced.

The team found that when the study trees were under stress, either because of a physical wound or because of exposure to an irritant such as ozone pollution, they began sharply increasing their uptake of oVOCs.

At the same time, changes took place in expression levels of certain genes that indicated heightened metabolic activity in the poplars.

The uptake of oVOCs, the scientists concluded, appeared to be part of a larger metabolic cycle.

Plants can produce chemicals to protect themselves from irritants and repel invaders such as insects, much as a human body may increase its production of white blood cells in reaction to an infection.

But these chemicals, if produced in enough quantity, can become toxic to the plant itself.

In order to metabolize these chemicals, the plants start increasing the levels of enzymes that transform the chemicals into less toxic substances.

At the same time, as it turns out, the plant draws down more oVOCs, which can be metabolized by the enzymes.

"Our results show that plants can actually adjust their metabolism and increase their uptake of atmospheric chemicals as a response to various types of stress," says Chhandak Basu of the University of Northern Colorado, a co-author.

"This complex metabolic process within plants has the side effect of cleansing our atmosphere."

Once they understood the extent to which plants absorb oVOCs, the research team fed the information into a computer model that simulates chemicals in the atmosphere worldwide.

The results indicated that, on a global level, plants are taking in 36 percent more oVOCs than had previously been accounted for in studies of atmospheric chemistry.

Additionally, since plants are directly removing the oVOCs, fewer of the compounds are evolving into aerosols.

"This really transforms our understanding of some fundamental processes taking place in our atmosphere," Karl says.

Journal Reference:

1. T. Karl, P. Harley, L. Emmons, B. Thornton, A. Guenther, C. Basu, A. Turnipseed, K. Jardine. Efficient Atmospheric Cleansing of Oxidized Organic Trace Gases by Vegetation. Science, 2010; DOI: 10.1126/science.1192534

Courtesy: ScienceDaily

Risk Gene for Severe Heart Disease Discovered

Research led by Klaus Stark and Christian Hengstenberg of the University of Regensburg identified a common variant of the cardiovascular heat shock protein gene, HSPB7, which was found to increase risk for dilated cardiomyopathy by almost 50%. Their paper appears on October 28 in the open-access journal PLoS Genetics.

Per year, about 6 in 100,000 individuals develop dilated cardiomyopathy (DCM), with a higher prevalence in men. This disease is characterized by an enlarged, weakened heart, subsequently affecting the pumping capacity and often leading to chronic heart failure.

Those cases of DCM that occur in certain family groups are associated with a number of mutations affecting muscle cells. However, most cases are of unknown cause. To identify risk alleles for non-familial forms of DCM, an international collaboration of scientists analyzed the contribution of common gene variants to the more frequent, sporadic form of dilated cardiomyopathy, by conducting a large-scale genetic association study with more than 5,500 subjects. Different study groups from Germany and France contributed both well-characterized DCM patients and healthy controls. The HSPB7 gene was strongly associated with susceptibility to DCM.

The researchers concluded that, while genetic testing for this variant is not suitable to date, the findings are a first step towards supporting future preventive measures for this severe form of heart muscle disease.

Journal Reference:

1. Greg Gibson, Klaus Stark, Ulrike B. Esslinger, Wibke Reinhard, George Petrov, Thomas Winkler, Michel Komajda, Richard Isnard, Philippe Charron, Eric Villard, François Cambien, Laurence Tiret, Marie-Claude Aumont, Olivier Dubourg, Jean-Noël Trochu, Laurent Fauchier, Pascal DeGroote, Anette Richter, Bernhard Maisch, Thomas Wichter, Christa Zollbrecht, Martina Grassl, Heribert Schunkert, Patrick Linsel-Nitschke, Jeanette Erdmann, Jens Baumert, Thomas Illig, Norman Klopp, H.-Erich Wichmann, Christa Meisinger, Wolfgang Koenig, Peter Lichtner, Thomas Meitinger, Arne Schillert, Inke R. König, Roland Hetzer, Iris M. Heid, Vera Regitz-Zagrosek, Christian Hengstenberg. Genetic Association Study Identifies HSPB7 as a Risk Gene for Idiopathic Dilated Cardiomyopathy. PLoS Genetics, 2010; 6 (10): e1001167 DOI: 10.1371/journal.pgen.1001167

Courtesy: ScienceDaily

Discovery Has Potential to Boost Anti-Breast Cancer Drug Tamoxifen's Effectiveness

Scientists in London have found a potential new way of boosting the effectiveness of the anti-breast cancer drug, tamoxifen.

The work carried out by Professor Clare Isacke and her team at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR), and partly funded by AICR (Association for International Cancer Research) could open the door to new treatments for those who have developed a resistance to tamoxifen, and has been described as an important new discovery.

Many breast cancers require the female sex hormones oestrogen and progesterone. Described as: 'hormone sensitive' or 'hormone receptor positive' they can be treated with drugs that block the effects of oestrogen and progesterone, such as tamoxifen.

Tamoxifen is given to most women for five years after they are first diagnosed with breast cancer to help prevent the disease recurring.

However, some breast cancers are resistant to the drug, or can develop resistance over time, allowing the cancer to recur or continue growing. Professor Isacke's discovery could lead to new drugs that counteract this resistance.

AICR's Scientific Co-ordinator Dr Mark Matfield, explained that resistance to treatment is a major problem for cancer patients.

"These findings are an exciting and important new discovery, as they could potentially help in the development of new treatments for women who have become resistant to tamoxifen," he said.

More than a million women worldwide, are diagnosed with breast cancer every year, accounting for a tenth of all new cancers and nearly a quarter of all new female cancer cases. In the UK alone, breast cancer is now the most common cancer: in 2007 almost 45,000 women -- and 277 men -- were diagnosed with the disease.

Tamoxifen, developed more than 30 years ago to treat breast cancer, prevents oestrogen from stimulating the growth of breast cancer cells. It is prescribed for women who are ER positive. That means that oestrogen receptors (ER) have been found on their breast cancer cells. The oestrogen receptor is the part of the breast cancer cell that oestrogen attaches itself to, triggering a chain of events which can lead to the cell growing and dividing in an uncontrolled manner and forming a tumour.

Work from Professor Isacke's team, funded by AICR and Breakthrough Breast Cancer, focuses on situations where, even when oestrogen is not present, the oestrogen receptor can become activated.

In their current paper, published in the cancer journal Oncogene, they show that when a protein called RET is switched on, it can activate the oestrogen receptor in the absence of any oestrogen.

To confirm their findings from the laboratory, they took tissue samples from oestrogen positive breast cancer patients and found that they had increased levels of RET. They went on to show that reducing the levels of RET actually makes the breast cancer cells more sensitive to tamoxifen and more likely to die.

Speaking from the Breakthrough Breast Cancer Research Centre at the ICR, in London, where she leads the Molecular Cell Biology Team Professor Isacke said: "We are very excited by these findings. Our challenge now is to work out how RET activates the oestrogen receptor so that we can develop new treatments for tamoxifen-resistant breast cancers."

Journal Reference:

1. I Plaza-Menacho, A Morandi, D Robertson, S Pancholi, S Drury, M Dowsett, L-A Martin, C M Isacke. Targeting the receptor tyrosine kinase RET sensitizes breast cancer cells to tamoxifen treatment and reveals a role for RET in endocrine resistance. Oncogene, 2010; 29 (33): 4648 DOI: 10.1038/onc.2010.209

Courtesy: ScienceDaily

Gene's Location on Chromosome Plays Big Role in Shaping How an Organism's Traits Evolve

A gene's location on a chromosome plays a significant role in shaping how an organism's traits vary and evolve, according to findings by genome biologists at New York University's Center for Genomic and Systems Biology and Princeton University's Lewis-Sigler Institute for Integrative Genomics. Their research, which appears in the latest issue of the journal Science, suggests that evolution is less a function of what a physical trait is and more a result of where the genes that affect that trait reside in the genome.

Physical traits found in nature, such as height or eye color, vary genetically among individuals. While these traits may differ significantly across a population, only a few processes can explain what causes this variation -- namely, mutation, natural selection, and chance.

In the Science study, the NYU and Princeton researchers sought to understand, in greater detail, why traits differ in their amount of variation. But they also wanted to determine the parts of the genome that vary and how this affects expression of these physical traits. To do this, they analyzed the genome of the worm Caenorhabditis elegans (C. elegans). C. elegans is the first animal species whose genome was completely sequenced. It is therefore a model organism for studying genetics. In their analysis, the researchers measured approximately 16,000 traits in C. elegans. The traits were measures of how actively each gene was being expressed in the worms' cells.

The researchers began by asking if some traits were more likely than others to be susceptible to mutation, with some physical features thus more likely than others to vary. Different levels of mutation indeed explained some of their results. Their findings also revealed significant differences in the range of variation due to natural selection -- those traits that are vital to the health of the organism, such as the activity of genes required for the embryo to develop, were much less likely to vary than were those of less significance to its survival, such as the activity of genes required to smell specific odors.

However, these results left most of the pattern of variation in physical traits unexplained -- some important factor was missing.

To search for the missing explanation, the researchers considered the make-up of C. elegans' chromosomes -- specifically, where along its chromosomes its various genes resided.

Chromosomes hold thousands of genes, with some situated in the middle of their linear structure and others at either end. In their analysis, the NYU and Princeton researchers found that genes located in the middle of a chromosome were less likely to contribute to genetic variation of traits than were genes found at the ends. In other words, a gene's location on a chromosome influenced the range of physical differences among different traits.

The biologists also considered why location was a factor in the variation of physical traits. Using a mathematical model, they were able to show that genes located near lots of other genes are evolutionarily tied to their genomic neighbors. Specifically, natural selection, in which variation among vital genes is eliminated, also removes the differences in neighboring genes, regardless of their significance. In C. elegans, genes in the centers of chromosomes are tied to more neighbors than are genes near the ends of the chromosomes. As a result, the genes in the center are less able to harbor genetic variation.

The research was conducted by Matthew V. Rockman, an assistant professor at New York University's Department of Biology and Center for Genomics and Systems Biology as well as Sonja S. Skrovanek and Leonid Kruglyak, researchers at Princeton University's Lewis-Sigler Institute for Integrative Genomics, Department of Ecology and Evolutionary Biology, and Howard Hughes Medical Institute.

The study was supported by grants from the National Institutes of Health.

Journal Reference:

1. M. V. Rockman, S. S. Skrovanek, L. Kruglyak. Selection at Linked Sites Shapes Heritable Phenotypic Variation in C. elegans. Science, 2010; 330 (6002): 372 DOI: 10.1126/science.1194208

Courtesy: ScienceDaily

Carbon Dioxide Controls Earth's Temperature, New Modeling Study Shows

Water vapor and clouds are the major contributors to Earth's greenhouse effect, but a new atmosphere-ocean climate modeling study shows that the planet's temperature ultimately depends on the atmospheric level of carbon dioxide.

The study, conducted by Andrew Lacis and colleagues at NASA's Goddard Institute for Space Studies (GISS) in New York, examined the nature of Earth's greenhouse effect and clarified the role that greenhouse gases and clouds play in absorbing outgoing infrared radiation. Notably, the team identified non-condensing greenhouse gases -- such as carbon dioxide, methane, nitrous oxide, ozone, and chlorofluorocarbons -- as providing the core support for the terrestrial greenhouse effect.

Without non-condensing greenhouse gases, water vapor and clouds would be unable to provide the feedback mechanisms that amplify the greenhouse effect. The study's results are published Oct. 15 in Science.

A companion study led by GISS co-author Gavin Schmidt that has been accepted for publication in the Journal of Geophysical Research shows that carbon dioxide accounts for about 20 percent of the greenhouse effect, water vapor and clouds together account for 75 percent, and minor gases and aerosols make up the remaining five percent. However, it is the 25 percent non-condensing greenhouse gas component, which includes carbon dioxide, that is the key factor in sustaining Earth's greenhouse effect. By this accounting, carbon dioxide is responsible for 80 percent of the radiative forcing that sustains the Earth's greenhouse effect.

The climate forcing experiment described in Science was simple in design and concept -- all of the non-condensing greenhouse gases and aerosols were zeroed out, and the global climate model was run forward in time to see what would happen to the greenhouse effect.

Without the sustaining support by the non-condensing greenhouse gases, Earth's greenhouse effect collapsed as water vapor quickly precipitated from the atmosphere, plunging the model Earth into an icebound state -- a clear demonstration that water vapor, although contributing 50 percent of the total greenhouse warming, acts as a feedback process, and as such, cannot by itself uphold the Earth's greenhouse effect.

"Our climate modeling simulation should be viewed as an experiment in atmospheric physics, illustrating a cause and effect problem which allowed us to gain a better understanding of the working mechanics of Earth's greenhouse effect, and enabled us to demonstrate the direct relationship that exists between rising atmospheric carbon dioxide and rising global temperature," Lacis said.

The study ties in to the geologic record in which carbon dioxide levels have oscillated between approximately 180 parts per million during ice ages, and about 280 parts per million during warmer interglacial periods. To provide perspective to the nearly 1 C (1.8 F) increase in global temperature over the past century, it is estimated that the global mean temperature difference between the extremes of the ice age and interglacial periods is only about 5 C (9 F).

"When carbon dioxide increases, more water vapor returns to the atmosphere. This is what helped to melt the glaciers that once covered New York City," said co-author David Rind, of NASA's Goddard Institute for Space Studies. "Today we are in uncharted territory as carbon dioxide approaches 390 parts per million in what has been referred to as the 'superinterglacial.'"

"The bottom line is that atmospheric carbon dioxide acts as a thermostat in regulating the temperature of Earth," Lacis said. "The Intergovernmental Panel on Climate Change has fully documented the fact that industrial activity is responsible for the rapidly increasing levels of atmospheric carbon dioxide and other greenhouse gases. It is not surprising then that global warming can be linked directly to the observed increase in atmospheric carbon dioxide and to human industrial activity in general."

Journal Reference:

1. A. A. Lacis, G. A. Schmidt, D. Rind, R. A. Ruedy. Atmospheric CO₂: Principal Control Knob Governing Earth's Temperature. Science, 2010; 330 (6002): 356 DOI: 10.1126/science.1190653

Courtesy: ScienceDaily

Clue to Unusual Drug-Resistant Breast Cancers Found

Researchers at the University of Illinois at Chicago College of Medicine have found how gene expression that may contribute to drug resistance is ramped up in unusual types of breast tumors. Their findings may offer new therapy targets.

The study is published in the Oct. 8 issue of the Journal of Biological Chemistry, where it is designated a paper of the week.

Approximately 70 percent of breast cancers express the estrogen receptor. These "ER-positive" tumors usually respond to hormone-related therapies, such as tamoxifen or aromatase inhibitors. But not always.

"We were interested in a subset of ER-positive tumors that are unusually aggressive and also drug-resistant," said Jonna Frasor, assistant professor of physiology and biophysics at the UIC College of Medicine and principal investigator of the study.

Following up on earlier observations that these aggressive ER-positive tumors express genes that respond both to estrogen and inflammatory factors called cytokines, Frasor and her colleagues focused on the gene for a drug-transporter protein which is believed to pump chemotherapy drugs out of tumor cells, making them resistant.

It is unexpected to find estrogen and inflammatory proteins seemingly working together to drive the cancer's aggressiveness, says Madhumita Pradhan, a student in Frasor's lab and first author of the paper. In many cases, estrogen is known to be protective against inflammatory processes, Pradhan said.

The researchers showed that in breast cancer cells, an inflammatory protein called NFĸB and the estrogen receptor act together to increase expression of the transporter gene. And they were able to show how.

An area on a gene called a promoter acts as an on/off switch that determines whether the gene is transcribed and the protein it encodes is produced. The promoter has spaces called response elements, where molecules can attach and help to turn the switch on or off.

"We found that the estrogen receptor gets recruited to the promoter of this gene," Frasor said. "Once there, the ER allows NFĸB to be recruited to its own response element. Once the second molecule binds, it actually stabilizes the ER and the gene is turned on to a much greater extent than with the ER alone."

This novel mechanism could have important implications in the treatment of breast cancers in which inflammation and estrogen can promote cancer progression, Frasor said.

Journal Reference:

1. M. Pradhan, L. A. Bembinster, S. C. Baumgarten, J. Frasor. Proinflammatory Cytokines Enhance Estrogen-dependent Expression of the Multidrug Transporter Gene ABCG2 through Estrogen Receptor and NF?B Cooperativity at Adjacent Response Elements. Journal of Biological Chemistry, 2010; 285 (41): 31100 DOI: 10.1074/jbc.M110.155309

Courtesy: ScienceDaily

Stem Cells Repair Damaged Spinal Cord Tissue

Researchers at Karolinska Institutet have shown how stem cells, together with other cells, repair damaged tissue in the mouse spinal cord. The results are of potential significance to the development of therapies for spinal cord injury.

There is hope that damage to the spinal cord and brain will one day be treatable using stem cells (i.e. immature cells that can develop into different cell types). Stem cell-like cells have been found in most parts of the adult human nervous system, although it is still unclear how much they contribute to the formation of new, functioning cells in adult individuals.

A joint study by Professor Jonas Frisén's research group at Karolinska Institutet and their colleagues from France and Japan, and published in Cell Stem Cell, shows how stem cells and several other cell types contribute to the formation of new spinal cord cells in mice and how this changes dramatically after trauma.

The research group has identified a type of stem cell, called an ependymal cell, in the spinal cord. They show that these cells are inactive in the healthy spinal cord, and that the cell formation that takes place does so mainly through the division of more mature cells. When the spinal cord is injured, however, these stem cells are activated to become the dominant source of new cells.

The stem cells then give rise to cells that form scar tissue and to a type of support cell that is an important component of spinal cord functionality. The scientists also show that a certain family of mature cells known as astrocytes produce large numbers of scar-forming cells after injury.

"The stem cells have a certain positive effect following injury, but not enough for spinal cord functionality to be restored," says Jonas Frisén. "One interesting question now is whether pharmaceutical compounds can be identified to stimulate the cells to form more support cells in order to improve functional recovery after a spinal trauma."

Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Journal Reference:

1. Fanie Barnabé-Heider, Christian Göritz, Hanna Sabelström, Hirohide Takebayashi, Frank W. Pfrieger, Konstantinos Meletis & Jonas Frisén. Origin of new glial cells in the intact and injured adult spinal cord. Cell Stem Cell, 8 October 2010 DOI: 10.1016/j.stem.2010.07.014

Courtesy: ScienceDaily

Microfluidic Devices Advance 3-D Tissue Engineering

A research team, co-headed by Dr. Woo Lee and Dr. Hongjun Wang of Stevens Institute of Technology, has published a paper describing a new method that generates three-dimensional (3D) tissue models for studying bacterial infection of orthopedic implants. Dr. Joung-Hyun Lee of Stevens, and Dr. Jeffrey Kaplan of the New Jersey Dental School, are co-authors of the research. Their paper, appearing in the journal Tissue Engineering, demonstrates a physiologically relevant approach for studying infection prevention strategies and emulating antibiotic delivery using 3D bone tissues cultured in microfluidic devices.

With over 1 million hip and knee replacement procedures being performed in the United States every year, orthopedic implants have become relatively common. Despite advances in implant design, hospitals have been unable to address bacterial infection, the leading cause of failure in orthopedic implants. A significant barrier to successfully developing infection-fighting drugs or biomaterials has been the inadequacy of laboratory equipment to create clinically relevant environment with traditional in vitro methods.

The researchers seeded 0.02 mL microfluidic channels with osteoblasts and inoculated the channels with Staphylococcus epidermis bacteria, a common pathogen in orthopedic infections. Nutrient solutions were pumped through the channels at a concentration and flow rate mimicking conditions within the human body. Bone tissue cells and bacteria within the channels were imaged with a microscope and effluent was analyzed for bacteria count.

Microfluidic devices, together with finely-tuned dynamic flow settings, have the potential to provide realistic bone tissue models in clinical scenarios. As opposed to the static 2D Petri dish surfaces, microfluidic channels present a realistic environment for cells to grow and adhere in three dimensions. Dynamic fluid motion through the channels -- with solutions potentially carrying antibiotics or other novel drugs -- further mimics real-world conditions previously unrealizable in a lab setting.

The research team is comprised of Dr. Woo Lee, George Meade Bond Professor in Chemical Engineering and Materials Science; Dr. Hongjun Wang, Assistant Professor of Biomedical Engineering; Dr. Joung-Hyun Lee, Research Associate and 2010 Ph.D. graduate of Stevens; and Dr. Jeffrey Kaplan, Associate Professor in the Department of Oral Biology at the New Jersey Dental School. Dr. Joung-Hyun Lee, as the first author of this paper, used her background in microfabrication to discover the conditions for growing bone tissues in the microfluidic device channels while integrating capabilities in the laboratories of Lee, Wang, and Kaplan. This research was sponsored the Nanoscale Interdisciplinary Research Team program of the National Science Foundation (NSF). Also, Dr. Lee and Dr. Wang are principal investigators on a new grant from the NSF Biomaterials program, awarded earlier this year. In this new project, they plan to use the newly developed 3D tissue model to evaluate the efficacy of inkjet-printed infection-preventing biomaterials.

The researchers' published paper is a preliminary demonstration of dynamic microfluidic cell cultures and work continues in the lab to establish successful applications of the technology and processes.

Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Journal Reference:

1. Joung-Hyun Lee, Hongjun Wang, Jeffrey B. Kaplan, Woo Y. Lee. Microfluidic Approach to Create Three-Dimensional Tissue Models for Biofilm-Related Infection of Orthopaedic Implants. Tissue Engineering Part C: Methods, 2010; : 100830144718098 DOI: 10.1089/ten.tec.2010.0285

Courtesy: ScienceDaily

Plants Kick-Started Evolutionary Drama of Earth's Oxygenation

An international team of scientists, exploiting pioneering techniques at Arizona State University, has taken a significant step toward unlocking the secrets of oxygenation of the Earth's oceans and atmosphere.

Evolution of the Earth's multitude of organisms is intimately linked to the rise of oxygen in the oceans and atmosphere. The new research indicates that the appearance of large predatory fish as well as vascular plants approximately 400 million years ago coincided with an increase in oxygen, to levels comparable to those we experience today. If so, then animals from before that time appeared and evolved under markedly lower oxygen conditions than previously thought.

The researchers, including collaborators from Harvard, Denmark, Sweden and the United Kingdom, made use of a method developed at ASU by Ariel Anbar, a professor in the department of chemistry and biochemistry and the School of Earth and Space Exploration in the College of Liberal Arts and Sciences, and his research group. The method can be used to estimate global oxygen levels in ancient oceans from the chemical composition of ancient seafloor sediments.

Their important findings are presented in a paper published in the Proceedings of the National Academy of Sciences (PNAS), titled "Devonian rise in atmospheric oxygen correlated to radiations of terrestrial plants and large predatory fish."

"There has been a lot of speculation over the years about whether or not oxygen in the atmosphere was steady or variable over the last 500 million years," explained Anbar, who leads ASU's Astrobiology Program. "This is the era during which animals and land plants emerged and flourished. So it's a profound question in understanding the history of life. These new findings not only suggest that oxygen levels varied, but also that the variation had direct consequences for the evolution of complex life."

The Earth is 4,500 million years old. Microbial life has probably thrived in the oceans for most of that time. However, until about 2,300 million years ago, the atmosphere contained only traces of oxygen. During that time, some microbes in the oceans likely produced oxygen as a byproduct of photosynthesis. But the quantities they produced were insufficient to accumulate much in the atmosphere and oceans. The situation changed with the "Great Oxidation Event," 2,300 million years ago. Oxygen levels rose again around 550 million years ago. The first animals appear in the fossil record at this time, marking the beginning of an era that geologists call the "Phanerozoic" -- a Greek word meaning "evident animals." This new work explores how oxygen levels changed during the Phanerozoic.

The new study was led by Tais W. Dahl while he was a postdoctoral scholar at Harvard. Dahl spent several months in Anbar's lab at ASU during his graduate research learning how to make the necessary measurements from Gwyneth Gordon, Ph.D., who is also an author of this paper. Other authors include geochemist Don Canfield, Dahl's Ph.D. mentor at the University of Southern Denmark, and paleontologist Andrew Knoll, Dahl's postdoctoral mentor at Harvard.

Dahl returned to ASU to perform the measurements for this study, which involved measuring the relative amounts of different isotopes of the element molybdenum in rocks called "black shales." These rocks are formed from ancient ocean sediments.

Isotopes are atoms of an element, in this case molybdenum, that differ only in their mass and therefore can be easily distinguished from one another. Molybdenum has seven stable isotopes. Chemical reactions fractionate heavy from light isotopes. For example, carbon 12 is enriched by three percent in plants relative to the carbon in carbon dioxide in the atmosphere. Similarly, molybdenum isotopes are fractionated during their removal from seawater into ocean sediments. The magnitude of this fractionation is sensitive to the presence of oxygen.

The data Dahl obtained at ASU reveal that there were at least two stages of oxygenation during the Phanerozoic, separated by the oxygenation event 400 million years ago. This inference from molybdenum isotopes is corroborated by the appearance of large (up to 30 feet long) predatory fish in the fossil record 400 million years ago, coincident with the rise in oxygen. Animals of that size consume energy rapidly, requiring high levels of oxygen for their metabolism. "Tais's data indicate that early animals evolved in an environment with less oxygen than today," said Anbar. The newly discovered oxygenation event therefore explains the puzzling appearance of these fish in the fossil record. "It's always satisfying when we can demonstrate how an environmental change drove biological evolution," Anbar explained.

"But the real kicker is that these data also show us the reverse -- that biological innovation can drive environmental change" continued Anbar. He points to the fact that vascular plants also appear in the fossil record around 400 million years ago. The bodies of such plants decompose with difficulty, making it easier for organic carbon to be buried in sediments. When that happens, the organic carbon -- produced by photosynthesis -- is not available for reaction with oxygen. The consequence is a rise in the amount of oxygen in the environment.

"It's a push-me-pull-you situation," explained Anbar. The biological innovation of vascular plants led to more carbon burial, and therefore to more oxygen. Then, the rise in oxygen made it possible for larger animals to evolve. "This is a great example of what we call the "co evolution" of life and the environment," enthused Anbar "Geoscientists talk about this idea a lot, but we rarely find such nice examples."

This work was supported by the Danish National Research Foundation, Danish Council for Independent Research, the Swedish Research Council, the NASA Astrobiology Institute team at ASU and the NASA Exobiology Program.

Journal Reference:

1. T. W. Dahl, E. U. Hammarlund, A. D. Anbar, D. P. G. Bond, B. C. Gill, G. W. Gordon, A. H. Knoll, A. T. Nielsen, N. H. Schovsbo, D. E. Canfield. Devonian rise in atmospheric oxygen correlated to the radiations of terrestrial plants and large predatory fish. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1011287107

Courtesy: ScienceDaily

How to Still Kill a Resistant Parasite

Scientists from the Institute of Tropical Medicine Antwerp in Belgium, in collaboration with colleagues from several developing countries, were able to restore a sleeping sickness parasite's susceptibility to drugs. The parasite causes sleeping sickness in cattle. Because it has become resistant against all currently available drugs, it causes enormous economic losses. Until now, that is.

Not only people suffer from sleeping sickness. Trypanosoma congolense, a nephew of the human parasite, infects livestock. Millions of people in sub-Saharan Africa depend on their livestock. Nagana, as sleeping sickness in livestock is called, is "a primary cause of rural poverty and food insecurity," according to the FAO. The three existing drugs against Nagana are virtually useless. The parasite has developed a way of eliminating the drug from its body. Development of new drugs would cost the pharmaceutical industry more than they would gain.

For years, the Institute of Tropical Medicine collaborates with partner institutes in developing countries all over the world. Together the scientists searched for substances that could block the drug elimination process. No easy task, because the parasite does not grow in the lab. But eventually they found two substances that reinvigorated one of the old medicines, ISM (isometamidium chloride). Both substances (oxytetracycline and enrofloxacine) are antibiotics that are affordable to poor countries. When used alone they are ineffective, but in combination with ISM they are deadly to the parasite.

The scientists first tested their approach in mice, and then in cattle. They inoculated three groups of six cattle with resistant trypanosomes and then treated them. The cattle that received ISM only, all got Nagana. Half the cattle that received ISM plus an antibiotic were cured. In the other animals, the parasite remained in the blood, but hardly detectable.

Fifty percent cure doesn't seem that much, but with a disease affecting three million cattle per year, often from owners barely surviving anyway, the difference is substantial.

The patent on oxytetracycline has expired, it is available on the African market and the farmers/herders are familiar with the drug. If the findings are confirmed -- always a condition in science -- the treatment can be implemented rapidly. Meanwhile the scientists screen close relatives of both antibiotics. They also test lower dosages and more practical ways of administration (during their study they gave intramuscular injections at two to three days interval during one month, which is unpractical in rural Africa).

Journal Reference:

1. Kiyoshi Kita, Vincent Delespaux, Hervé Sèna Vitouley, Tanguy Marcotty, Niko Speybroeck, Dirk Berkvens, Krisna Roy, Stanny Geerts, Peter Van den Bossche. Chemosensitization of Trypanosoma congolense Strains Resistant to Isometamidium Chloride by Tetracyclines and Enrofloxacin. PLoS Neglected Tropical Diseases, 2010; 4 (9): e828 DOI: 10.1371/journal.pntd.0000828

Courtesy: ScienceDaily

C-Met May Be a Biomarker for Metastatic Hepatocellular Carcinoma

Targeting c-Met may be a promising personalized treatment method for approximately 45 percent of patients with hepatocellular carcinoma (HCC) who have c-Met-positive tumors, according to study results presented at the Fourth AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

HCC is the most common primary malignant tumor of the liver; c-Met is a receptor for hepatocyte growth factor that appears to drive liver cancer growth, invasion and metastasis.

"Current therapies for HCC patients are 'one size fits all.' We propose that molecular profiling will enable better therapy for HCC patients with a c-Met positive tumor," said Hanning You, M.D., Ph.D., postdoctoral fellow working in the laboratory of C. Bart Rountree, M.D., in the departments of pediatrics and pharmacology, at the Pennsylvania State University College of Medicine, Hershey, Pa.

Using a preclinical translational study to validate c-Met as a target for HCC, You and colleagues found c-Met was highly overexpressed in metastatic liver cancer cells.

"By targeting c-Met we were able to suppress tumor growth in vivo and kill these metastatic liver cancer cells," said You.

Since c-Met inhibitor stopped proliferation and tumor growth of metastatic HCC cells, the researchers concluded that c-Met might be a potential personalized target of metastatic HCC. In addition, they found that results of a separate meta-analysis of six studies and 1,051 patients showed that c-Met activation is associated with poor prognosis in HCC.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by American Association for Cancer Research, via EurekAlert!, a service of AAAS.

Courtesy: ScienceDaily

Could Genetically Altered Trees, Plants Help Counter Global Warming?

Forests of genetically altered trees and other plants could sequester several billion tons of carbon from the atmosphere each year and so help ameliorate global warming, according to estimates published in the October issue of BioScience.

The study, by researchers at Lawrence Berkeley National Laboratory and Oak Ridge National Laboratory, outlines a variety of strategies for augmenting the processes that plants use to sequester carbon dioxide from the air and convert it into long-lived forms of carbon, first in vegetation and ultimately in soil.

Besides increasing the efficiency of plants' absorption of light, researchers might be able to genetically alter plants so they send more carbon into their roots--where some may be converted into soil carbon and remain out of circulation for centuries. Other possibilities include altering plants so that they can better withstand the stresses of growing on marginal land, and so that they yield improved bioenergy and food crops. Such innovations might, in combination, boost substantially the amount of carbon that vegetation naturally extracts from air, according to the authors' estimates.

The researchers stress that the use of genetically engineered plants for carbon sequestration is only one of many policy initiatives and technical tools that might boost the carbon sequestration already occurring in natural vegetation and crops.

The article, by Christer Jansson, Stan D. Wullschleger, Udaya C. Kalluri, and Gerald A. Tuskan, is the first in a Special Section in the October BioScience that includes several perspectives on the prospects for enhancing biological carbon sequestration. Other articles in the section analyze the substantial ecological and economic constraints that limit such efforts. One article discusses the prospects for sequestering carbon by culturing algae to produce biofuel feedstocks; one proposes a modification of the current regulatory climate for producing genetically engineered trees in the United States; and one discusses societal perceptions of the issues surrounding the use of genetically altered organisms to ameliorate warming attributed to the buildup of greenhouse gases.

Journal Reference:

1. Christer Jansson, Stan D. Wullschleger, Udaya C. Kalluri, and Gerald A. Tuskan. Phytosequestration: Carbon Biosequestration by Plants and the Prospects of Genetic Engineering. BioScience, October 2010

Courtesy: ScienceDaily

Adult Stem Cells That Do Not Age

Biomedical researchers at the University at Buffalo have engineered adult stem cells that scientists can grow continuously in culture, a discovery that could speed development of cost-effective treatments for diseases including heart disease, diabetes, immune disorders and neurodegenerative diseases.

UB scientists created the new cell lines -- named "MSC Universal" -- by genetically altering mesenchymal stem cells, which are found in bone marrow and can differentiate into cell types including bone, cartilage, muscle, fat, and beta-pancreatic islet cells.

The researchers say the breakthrough overcomes a frustrating barrier to progress in the field of regenerative medicine: The difficulty of growing adult stem cells for clinical applications.

Because mesenchymal stem cells have a limited life span in laboratory cultures, scientists and doctors who use the cells in research and treatments must continuously obtain fresh samples from bone marrow donors, a process both expensive and time-consuming. In addition, mesenchymal stem cells from different donors can vary in performance.

The cells that UB researchers modified show no signs of aging in culture, but otherwise appear to function as regular mesenchymal stem cells do -- including by conferring therapeutic benefits in an animal study of heart disease. Despite their propensity to proliferate in the laboratory, MSC-Universal cells did not form tumors in animal testing.

"Our stem cell research is application-driven," says Techung Lee, PhD, UB associate professor of biochemistry and biomedical engineering in the School of Medicine and Biomedical Sciences and the School of Engineering and Applied Sciences, who led the project. "If you want to make stem cell therapies feasible, affordable and reproducible, we know you have to overcome a few hurdles. Part of the problem in our health care industry is that you have a treatment, but it often costs too much. In the case of stem cell treatments, isolating stem cells is very expensive. The cells we have engineered grow continuously in the laboratory, which brings down the price of treatments."

UB has applied for a patent to protect Lee's discovery, and the university's Office of Science, Technology Transfer and Economic Outreach (UB STOR) is discussing potential license agreements with companies interested in commercializing MSC-Universal.

Stem cells help regenerate or repair damaged tissues, primarily by releasing growth factors that encourage existing cells in the human body to function and grow.

Lee's ongoing work indicates that this feature makes it feasible to repair tissue damage by injecting mesenchymal stem cells into skeletal muscle, a less invasive procedure than injecting the cells directly into an organ requiring repair. In a rodent model of heart failure, Lee and collaborators showed that intramuscular delivery of mesenchymal stem cells improved heart chamber function and reduced scar tissue formation.

UB STOR commercialization manager Michael Fowler believes MSC-Universal could be key to bringing new regenerative therapies to the market. The modified cells could provide health care professionals and pharmaceutical companies with an unlimited supply of stem cells for therapeutic purposes, Fowler says.

Lee says his research team has generated two lines of MSC-Universal cells: a human line and a porcine line. Using the engineering technique he and colleagues developed, scientists can generate an MSC-Universal line from any donor sample of mesenchymal stem cells, he says. "I imagine that if these cells become routinely used in the future, one can generate a line from each ethnic group for each gender for people to choose from," Lee says.

The research was funded by the National Institutes of Health and New York State Stem Cell Science (NYSTEM).

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University at Buffalo, via EurekAlert!, a service of AAAS.

Courtesy: ScienceDaily

Cellular Structural Molecule Can Be Toxic: Makes Pneumonia Worse

A structural molecule and the cellular pump that regulates its levels influence the severity of pneumonia and could provide new ways of treating the lung infection, which is a leading cause of hospitalization and death, according to scientists at the University of Pittsburgh and the University of Iowa.

Their findings are available online in Nature Medicine.

Despite decades of research, there has been little new information on what biological mechanisms make bacterial pneumonia get worse, said senior author Rama K. Mallampalli, M.D., a professor in the Acute Lung Injury Center of Excellence, University of Pittsburgh School of Medicine, and pulmonary division chief at the VA Pittsburgh Healthcare System.

"Our study reveals some of the molecular steps that can lead to lung injury after infection and shows us new avenues for pneumonia therapy that don't have to target bacteria, as antibiotics do," he said.

The researchers found that lung fluid from humans and mice with pneumonia contains abnormally high levels of cardiolipin, a structural molecule that is typically found in the membranes of energy-making mitochondria. A carrier protein called Atp8b1 transports the molecule from the lung fluid into the cell, acting as a pump that regulates cardiolipin levels.

Infection leads to the death of cells, and that releases cellular components, including cardiolipin, into the surrounding fluid, Dr. Mallampalli explained. The carrier protein can become overwhelmed, allowing cardiolipin levels to climb. The excess cardiolipin disrupts the function of surfactant, a lubricant that is necessary for the proper expansion and contraction of the lungs during breathing, which can lead to more tissue damage.

When cardiolipin was administered to mice, their lung function became impaired and their lung tissue became damaged akin to what is seen with pneumonia. Similarly, mice with a mutation in the carrier protein gene were more likely to have severe pneumonia.

"This research was inspired by the knowledge that some people have a mutation in this protein, a condition called Byler's disease, and they are more likely to get pneumonia," Dr. Mallampalli noted.

In other experiments, mice with the gene mutation and pneumonia were treated with an engineered protein fragment that attached to the cardiolipin binding site, preventing the molecule from interacting with surfactant and ultimately reducing lung injury and improving survival.

"A similar strategy might work in people and could be a very useful option at a time when we have bacterial strains that are resistant to multiple antibiotics," said Mark Gladwin, M.D., chief of the Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine.

Dr. Mallampalli and his colleagues are now working on ways to deliver proteins into the lung that tightly bind cardiolipin with the goal of translating this approach for testing in pneumonia patients.

The study team includes lead authors Nancy B. Ray, Ph.D., and Lakshmi Durairaj, M.D., and others from the University of Iowa; and Bill B. Chen, Ph.D., and Bryan J. McVerry, M.D., of the Acute Lung Injury Center of Excellence at Pitt, and others from the University of Pittsburgh.

The research was funded by the U.S. Department of Veterans Affairs and the National Institutes of Health.

Journal Reference:

1. Nancy B Ray, Lakshmi Durairaj, Bill B Chen, Bryan J McVerry, Alan J Ryan, Michael Donahoe, Alisa K Waltenbaugh, Christopher P O'Donnell, Florita C Henderson, Christopher A Etscheidt, Diann M McCoy, Marianna Agassandian, Emily C Hayes-Rowan, Tiffany A Coon, Phillip L Butler, Lokesh Gakhar, Satya N Mathur, Jessica C Sieren, Yulia Y Tyurina, Valerian E Kagan, Geoffrey McLennan, Rama K Mallampalli. Dynamic regulation of cardiolipin by the lipid pump Atp8b1 determines the severity of lung injury in experimental pneumonia. Nature Medicine, 2010; DOI: 10.1038/nm.2213

Courtesy: ScienceDaily