sid_melo blogreen: 05/27/14

terça-feira, 27 de maio de 2014

'Virtual human' shows that stiff arteries can explain cause of high blood pressure

High blood pressure is highly age-related and affects more than 1 billion people worldwide. But doctors can't fully explain the cause of 90 per cent of all cases. A computer model of a "virtual human" suggests that stiff arteries alone are enough to cause high blood pressure.

"Our results suggest that arterial stiffness represents a major therapeutic target. This is contrary to existing models, which typically explain high blood pressure in terms of defective kidney function," says Klas Pettersen, a researcher at the Norwegian University of Life Sciences and first author of the study, recently published in PLOS Computational Biology.

High blood pressure is a major source of morbidity and mortality, because it makes individuals more prone to heart failure, stroke and kidney disease.

When blood pressure travels down the aorta from the heart, a special group of cells in the aortic wall, called baroreceptors, sense the pressure in this stretch of the aortic wall and send signals with this information to the nervous system.

If the blood pressure is too high, these cells send stronger signals and the body is able to lower blood pressure. However, if the aorta gets stiffer, as typically happens with age, this stretch of the aorta is not as sensitive as it once was in measuring blood pressure. Thus, although a person's blood pressure may have increased, the baroreceptors do not signal as intensively as they should and the body does not get the message to lower blood pressure.

"With the stiffening of the wall that follows aging, these sensors become less able to send signals that reflect the actual blood pressure. Our mathematical model predicts the quantitative effects of this process on blood pressure," says Pettersen.

"If our hypothesis is proven right, arterial stiffness and baroreceptor signaling will become hotspot targets for the treatment of high blood pressure and the development of new medicines and medical devices," says Stig W. Omholt from the Norwegian University of Science and Technology, who was the senior investigator of the research project.

With the use of existing experimental data and models of the aging human aorta, the researchers were able to show quantitatively how the stiffening of the aorta with age causes the baroreceptors to misinform the central nervous system about blood pressure, thus preventing the system from downregulating blood pressure. The model predictions were compared with data from the Nord-Trøndelag Health Study (HUNT2), which is composed of information on the health history of 74,000 people, including blood sample collection from 65,000 people.

NTNU's Omholt says that the study is a good example of how very complex human disease can be understood by use of mathematical models and thus allow for much better treatment strategies.

"If we are to succeed in developing predictive, preventive and participatory medicine envisioned by so many, there is no substitute for building much stronger transdisciplinary ties between the life sciences, the mathematical sciences and engineering across the whole spectrum of basic, translational and applied research. And mathematical models of the human physiology will be at the core of this development," he says.

Story Source:

The above story is based on materials provided by Norwegian University of Science and Technology. Note: Materials may be edited for content and length.

Journal Reference:

Klas H. Pettersen, Scott M. Bugenhagen, Javaid Nauman, Daniel A. Beard, Stig W. Omholt. Arterial Stiffening Provides Sufficient Explanation for Primary Hypertension. PLoS Computational Biology, 2014; 10 (5): e1003634 DOI: 10.1371/journal.pcbi.1003634

Heavily decorated classrooms disrupt attention and learning in young children

Click to enlarge

Published in Psychological Science, Carnegie Mellon University researchers looked at whether classroom displays affected children's ability to maintain focused attention during instruction and to learn the lesson content. They found that children in highly decorated classrooms were more distracted, spent more time off-task and demonstrated smaller learning gains than when the decorations were removed (top image).

Maps, number lines, shapes, artwork and other materials tend to cover elementary classroom walls. However, new research from Carnegie Mellon University shows that too much of a good thing may end up disrupting attention and learning in young children.

Published in Psychological Science, Carnegie Mellon's Anna V. Fisher, Karrie E. Godwin and Howard Seltman looked at whether classroom displays affected children's ability to maintain focus during instruction and to learn the lesson content. They found that children in highly decorated classrooms were more distracted, spent more time off-task and demonstrated smaller learning gains than when the decorations were removed.

"Young children spend a lot of time -- usually the whole day -- in the same classroom, and we have shown that a classroom's visual environment can affect how much children learn," said Fisher, lead author and associate professor of psychology in the Dietrich College of Humanities and Social Sciences.

Should teachers take down their visual displays based on the findings of this study?

"We do not suggest by any means that this is the answer to all educational problems. Furthermore, additional research is needed to know what effect the classroom visual environment has on children's attention and learning in real classrooms," Fisher said "Therefore, I would suggest that instead of removing all decorations, teachers should consider whether some of their visual displays may be distracting to young children. "

For the study, 24 kindergarten students were placed in laboratory classrooms for six introductory science lessons on topics they were unfamiliar with. Three lessons were taught in a heavily decorated classroom, and three lessons were given in a sparse classroom.

The results showed that while children learned in both classroom types, they learned more when the room was not heavily decorated. Specifically, children's accuracy on the test questions was higher in the sparse classroom(55 percent correct) than in the decorated classroom(42 percent correct).

"We were also interested in finding out if the visual displays were removed, whether the children's attention would shift to another distraction, such as talking to their peers, and if the total amount of time they were distracted would remain the same," said Godwin, a Ph.D. candidate in psychology and fellow of the Program in Interdisciplinary Education Research (PIER).

However, when the researchers tallied all of the time children spent off-task in both types of classrooms, the rate of off-task behavior was higher in the decorated classroom (38.6 percent time spent off-task) than in the sparse classroom (28.4 percent time spent off-task).

The researchers hope these findings lead to further studies into developing guidelines to help teachers optimally design classrooms.

Story Source:

The above story is based on materials provided by Carnegie Mellon University. Note: Materials may be edited for content and length.

Journal Reference:

A. V. Fisher, K. E. Godwin, H. Seltman. Visual Environment, Attention Allocation, and Learning in Young Children: When Too Much of a Good Thing May Be Bad. Psychological Science, 2014; DOI: 10.1177/0956797614533801

An area's level of poverty or wealth may affect the distribution of cancer types

A new analysis has found that certain cancers are more concentrated in areas with high poverty, while other cancers arise more often in wealthy regions. Also, areas with higher poverty had lower cancer incidence and higher mortality than areas with lower poverty. Published early online in Cancer, a peer-reviewed journal of the American Cancer Society, the study's findings demonstrate the importance of including measures of socioeconomic status in national cancer surveillance efforts.

Overall, socioeconomic status is not related to cancer risk -- cancer strikes the rich and poor alike. However, socioeconomic status does seem to influence the type of cancer a person may develop. To look closely at the issue, Francis Boscoe, PhD, of the New York State Cancer Registry and his colleagues compared people living in areas with the highest poverty with those living in areas with the lowest poverty. The investigators assigned nearly three million tumors diagnosed between 2005 and 2009 from 16 states plus Los Angeles (an area covering 42 percent of the US population) into one of four groupings based on the poverty rate of the residential census tract at time of diagnosis.

For all cancer types combined, there was a negligible association between cancer incidence and poverty; however, 32 of 39 cancer types showed a significant association with poverty (14 positively associated and 18 negatively associated). Certain cancers -- Kaposi sarcoma and cancers of the larynx, cervix, penis, and liver -- were more likely in the poorest neighborhoods, while other cancers -- melanoma, thyroid, other non-epithelial skin, and testis -- were more likely in the wealthiest neighborhoods. "At first glance, the effects seem to cancel one another out. But the cancers more associated with poverty have lower incidence and higher mortality, and those associated with wealth have higher incidence and lower mortality," explained Dr. Boscoe. "When it comes to cancer, the poor are more likely to die of the disease while the affluent are more likely to die with the disease."

Dr. Boscoe noted that recent gains in technology have made it much easier to link patient addresses with neighborhood characteristics, therefore making it possible to incorporate socioeconomic status into cancer surveillance. "Our hope is that our paper will illustrate the value and necessity of doing this routinely in the future," he said.

Story Source:

The above story is based on materials provided by Wiley. Note: Materials may be edited for content and length.

Journal Reference:

Francis P. Boscoe, Christopher J. Johnson, Recinda L. Sherman, David G. Stinchcomb, Ge Lin, Kevin A. Henry. The relationship between area poverty rate and site-specific cancer incidence in the United States. Cancer, 2014; DOI: 10.1002/cncr.28632

Novel home cleaning method to reduce asthma

A team of researchers from the University of South Carolina received two patents for a new method to rid carpets, mattresses and other furniture of harmful allergens and pests that cause asthma.

The patents (Methods and Compositions for Eliminating Allergens and Allergen-Producing Organisms) are the work of Michael Matthews, Jian Zhang and Allan Quick and uses carbon dioxide (CO₂) to "freeze clean" home fabrics. The process deactivates proteins found in pet dander and can remove smoke residue and other allergy-causing substances. The freezing process also kills dust mites embedded in carpets and mattresses, which feed off human skin particles and are a major cause of asthma.

The researchers are currently perfecting the application method, which utilizes CO2 vapor sprayed directly on fabric. The vapor cools on expansion to form tiny micro-pellets of dry ice that are quickly vacuumed up and the result is completely dry fabric free of allergy-causing agents. Early tests suggest a single cleaning treatment lasts approximately six months and does no harm to the fabric.

The work is funded with multiple external grants, including two from the National Institutes of Health.

About 7 million children, more than 9 percent of the entire child population in the U.S., suffer from asthma, according to the Centers for Disease Control. Asthma rates are even higher for minority and low-income children and asthma attacks also are responsible for 1.8 million emergency room visits each year.

Matthews, a professor of chemical engineering at USC's College of Engineering and Computing, said the method could eventually be ordered by physicians as an effective intervention for children with asthma.

"Our original concept, both in research and in our startup, was to commercialize carbon dioxide technology for medical sterilization," Matthews said. "However, we realized that there was a critical national need to address the removal of asthma triggers from the home. These triggers, which are actually proteins produced by pets and pests, can be removed with our technology."

Story Source:

The above story is based on materials provided by University of South Carolina. Note: Materials may be edited for content and length.

How DNA is 'edited' to correct genetic diseases

May 26 / 2014

University of Bristol

A major step forward in our understanding of how enzymes 'edit' genes has been made by an international team of researchers, paving the way for correcting genetic diseases in patients. Researchers have observed the process by which a class of enzymes called CRISPR -- pronounced 'crisper' -- bind and alter the structure of DNA. The results provide a vital piece of the puzzle if these genome editing tools are ultimately going to be used to correct genetic diseases in humans.

An illustration of DNA attached to magnetic beads, as used in the single molecule microscope.

An international team of scientists has made a major step forward in our understanding of how enzymes 'edit' genes, paving the way for correcting genetic diseases in patients.

Researchers at the Universities of Bristol, Münster and the Lithuanian Institute of Biotechnology have observed the process by which a class of enzymes called CRISPR -- pronounced 'crisper' -- bind and alter the structure of DNA.

The results, published in the Proceedings of the National Academy of Sciences (PNAS), provide a vital piece of the puzzle if these genome editing tools are ultimately going to be used to correct genetic diseases in humans.

CRISPR enzymes were first discovered in bacteria in the 1980s as an immune defence used by bacteria against invading viruses. Scientists have more recently shown that one type of CRISPR enzyme -- Cas9 -- can be used to edit the human genome -- the complete set of genetic information for humans.

These enzymes have been tailored to accurately target a single combination of letters within the three billion base pairs of the DNA molecule. This is the equivalent of correcting a single misspelt word in a 23-volume encyclopaedia.

To find this needle in a haystack, CRISPR enzymes use a molecule of RNA -- a nucleic acid similar in structure to DNA. The targeting process requires the CRISPR enzymes to pull apart the DNA strands and insert the RNA to form a sequence-specific structure called an 'R-loop'.

The global team tested the R-loop model using specially modified microscopes in which single DNA molecules are stretched in a magnetic field. By altering the twisting force on the DNA, the researchers could directly monitor R-loop formation events by individual CRISPR enzymes.

This allowed them to reveal previously hidden steps in the process and to probe the influence of the sequence of DNA bases.

Professor Mark Szczelkun, from Bristol University's School of Biochemistry, said: "An important challenge in exploiting these exciting genome editing tools is ensuring that only one specific location in a genome is targeted.

"Our single molecule assays have led to a greater understanding of the influence of DNA sequence on R-loop formation. In the future this will help in the rational re-engineering of CRISPR enzymes to increase their accuracy and minimise off-target effects. This will be vital if we are to ultimately apply these tools to correct genetic diseases in patients."

The work was funded at the University of Bristol by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust.

Story Source:

The above story is based on materials provided by University of Bristol. Note: Materials may be edited for content and length.

Journal Reference:

Mark D. Szczelkuna, Maria S. Tikhomirovab, Tomas Sinkunasd, Giedrius Gasiunasd, Tautvydas Karvelisd, Patrizia Pscherac, Virginijus Siksnysd and Ralf Seidel. Direct observation of R-loop formation by single RNA-guided Cas9 and Cascade effector complexes. PNAS, May 2014

Inhaling hypertonic saline decreases hospital admissions in children with bronchiolitis

May 26 / 2014

Children's Hospital Los Angeles Saban Research Institute

Infants with bronchiolitis who were treated with inhaled hypertonic saline in the emergency department (ED) were less likely to require admission to the hospital compared to infants treated with normal saline. Bronchiolitis is a respiratory infection common in infants and young children that results in approximately 150,000 hospitalizations each year, with an estimated cost of $500 million.

This is Susan Wu, M.D.

A team of researchers, led by physicians from Children's Hospital Los Angeles, have found that infants with bronchiolitis who were treated with inhaled hypertonic saline in the emergency department (ED) were less likely to require admission to the hospital compared to infants treated with normal saline.

The study, conducted at Children's Hospital Los Angeles and UCSF Benioff Children's Hospital Oakland, will be published in JAMA Pediatrics on May 26.

Bronchiolitis is a respiratory infection common in infants and young children that results in approximately 150,000 hospitalizations each year, with an estimated cost of $500 million.

"Previous studies have shown positive effects of using hypertonic saline, a concentrated salt solution, on infants and young children with bronchiolitis," said lead author, Susan Wu, MD, with The Saban Research Institute of Children's Hospital Los Angeles. "What is unique about this study is that we looked at the effect of administering hypertonic saline in the ED and then considered its effect on hospital admission."

The investigators treated 408 babies and young children; 197 received normal saline and 211 received 3% hypertonic saline. Patients were treated with their assigned intervention up to three times in the ED. Those admitted continued to receive the therapy every eight hours until discharge.

Investigators found that 42.6% of patients treated with normal saline required hospital admission compared with 28.9% of patients treated with hypertonic saline.

"We found that infants and young children with bronchiolitis treated with nebulized hypertonic saline in the ED were less likely to require hospitalization," said Wu, who is also an assistant professor of Clinical Pediatrics at the Keck School of Medicine of the University of Southern California. "It's gratifying to find an inexpensive yet effective therapy that helps patients while also reducing the cost of healthcare."

Story Source:

The above story is based on materials provided by Children's Hospital Los Angeles Saban Research Institute. Note: Materials may be edited for content and length.

Journal Reference:

Susan Wu, Chris Baker, Michael E. Lang, Sheree M. Schrager, Fasha F. Liley, Carmel Papa, Valerie Mira, Ara Balkian, Wilbert H. Mason. Nebulized Hypertonic Saline for Bronchiolitis. JAMA Pediatrics, 2014; DOI: 10.1001/jamapediatrics.2014.301

Melatonin makes old bones stronger, research shows

May 26 / 2014

McGill University

Melatonin supplements may make bones stronger in old rats, research shows. This suggests a possible avenue for the prevention of osteoporosis. Bones are built up by certain cells known as osteoblasts during the daytime and broken down by others (osteoclasts) at night. As we age, we sleep less, and so the cells that break down the bones are more active. By giving old rats melatonin supplements to regulate their circadian rhythms, the researchers have been able to make their bones denser, less brittle and more flexible.

McGill researchers have shown that melatonin supplements may make bones stronger in old rats. This suggests a possible avenue for the prevention of osteoporosis. Bones are built up by certain cells known as osteoblasts during the daytime and broken down by others (osteoclasts) at night. As we age, we sleep less, and so the cells that break down the bones are more active. By giving old rats melatonin supplements to regulate their circadian rhythms, the McGill researchers have been able to make their bones denser, less brittle and more flexible. Next step is to explore whether melatonin supplements prevent bone breakdown or can actually repair damage.

Research on elderly rats suggests possible avenue for prevention of osteoporosis

Faleh Tamimi, a professor in McGill's School of Dentistry, is the leader of a research team that has just discovered that melatonin supplements make bones stronger in elderly rats and therefore, potentially, in elderly humans too. "Old rats are tedious to work with because they get sick a lot and that means they also cost a lot more. But if you're interested in diseases like osteoporosis, they're an essential part of the process."

Dem bones, dem bones, dem dry bones -- sleep and bone regulation

The process of bone breakdown and buildup is affected by our circadian rhythms. The cells which break down our bones (known as osteoclasts) are more active at night, while those responsible for bone formation (osteoblasts) are more active during daylight hours. "As we age, we sleep less well, which means that the osteoclasts are more active," says Tamimi. "This tends to speed up the process of bone breakdown."

It is already well established that melatonin plays a role in regulating our body clocks and can potentially help us sleep better. So the researchers suspected that a melatonin supplement would help regulate the circadian rhythms of the elderly rats, thus reducing the activity of the osteoclasts and slowing down the process of bone breakdown. And that is exactly what they found.

22-month-old rats are the equivalent of 60-year-old humans

Researchers at the University of Madrid, where the rats were housed, gave twenty 22-month-old male rats (the equivalent of 60 year-old humans) melatonin supplements diluted in water for 10 weeks (the equivalent of six years in human years). The femurs taken from the elderly rats which had received the melatonin supplements were then compared with those of a control group (which had not received the supplements) using a series of tests to measure bone density and strength.

The researchers found that there was a significant increase in both bone volume and density among the rats that had received melatonin supplements. As a result, it took much more force to break the bones of rats that had taken the melatonin supplements, a finding that suggests to the researchers that melatonin may prove a useful tool in combatting osteoporosis.

For Tamimi and his colleagues the next big question is whether melatonin is preventing or actually reversing the process of bone breakdown. "Until there is more research as well as clinical trials to determine how exactly the melatonin is working, we can't recommend that people with osteoporosis go ahead and simply take melatonin supplements," says Tamimi. "I am applying for funding to pursue the research and we hope to have answers soon."

Story Source:

The above story is based on materials provided by McGill University. Note: Materials may be edited for content and length.

Journal Reference:

ISABEL F TRESGUERRES, Faleh Tamimi, Hazem Eimar, Jake Barralet, Santiago Prieto, Jesus Torres, Jose Luis Calvo-Guirado, Jesús Angel Fernández-Tresguerres. Melatonin dietary supplement as an anti-aging therapy for age-related bone loss. Rejuvenation Research, 2014; 140311120122003 DOI: 10.1089/rej.2013.1542

Neurons can use local stores for communication needs

May 26 / 2014

Rockefeller University Press

Neurons can utilize a supremely localized internal store of calcium to initiate the secretion of neuropeptides, one class of signaling molecules through which neurons communicate with each other and with other cells, researchers have shown. Neuropeptides are released from neurons through a process that—like other secretory events—is triggered primarily by the influx of calcium into the neuron through voltage-gated channels.

The localization of ryanodine receptors (red) in an isolated nerve terminal from the posterior pituitary gland is depicted in this image.

Researchers reveal that neurons can utilize a supremely localized internal store of calcium to initiate the secretion of neuropeptides, one class of signaling molecules through which neurons communicate with each other and with other cells. The study appears in The Journal of General Physiology.

Neuropeptides are released from neurons through a process that -- like other secretory events -- is triggered primarily by the influx of calcium into the neuron through voltage-gated channels. Although neuropeptides are stored in large dense core vesicles (LDCVs) that also contain large amounts of calcium, it has been unclear whether these locally based calcium supplies can also be used to modulate secretion.

A team of researchers led by José Lemos from the University of Massachusetts Medical School examined the mechanisms at play during secretion of vasopressin from nerve terminals in the posterior pituitary gland, which releases the neuropeptide into the blood so that it can make its way to the kidney and regulate water retention. The researchers found that certain intracellular calcium channels known as ryanodine receptors are likely responsible for mobilizing calcium from LDCVs to facilitate vasopressin release. The findings indicate that neurons have a greater capacity than previously appreciated to fine-tune the release of neuropeptides and thereby their communications with other cells.

Story Source:

The above story is based on materials provided by Rockefeller University Press. Note: Materials may be edited for content and length.

Journal Reference:

J. M. McNally, E. E. Custer, S. Ortiz-Miranda, D. J. Woodbury, S. D. Kraner, B. M. Salzberg, J. R. Lemos. Functional ryanodine receptors in the membranes of neurohypophysial secretory granules. The Journal of General Physiology, 2014; 143 (6): 693 DOI: 10.1085/jgp.201311110

Promising approach to slow brain degeneration in Huntington's disease uncovered

May 25 / 2014

Canadian Association for Neuroscience

Blocking a specific class of glutamate receptors can improve motor learning and coordination, and prevent cell death in animal models of Huntington's disease, research shows. As Huntington's disease is an inherited condition that can be detected decades before any clinical symptoms are seen in humans, this research could lead to preventive treatments that will delay the onset of symptoms and neurodegeneration.

Research presented by Dr. Lynn Raymond, from the University of British Columbia, shows that blocking a specific class of glutamate receptors, called extrasynaptic NMDA receptors, can improve motor learning and coordination, and prevent cell death in animal models of Huntington disease. As Huntington disease is an inherited condition that can be detected decades before any clinical symptoms are seen in humans, a better understanding of the earliest changes in brain cell (neuronal) function, and the molecular pathways underlying those changes, could lead to preventive treatments that delay the onset of symptoms and neurodegeneration.

"After more than a decade of research on the pre-symptomatic phase of Huntington disease, markers are being developed to facilitate assessment of interventional therapy in individuals carrying the genetic mutation for Huntington disease, before they become ill. This will make it possible to delay onset of disease," says Dr. Raymond. These results were presented at the 2014 Canadian Neuroscience Meeting, the 8th annual meeting of the Canadian Association for Neuroscience -- Association Canadienne des Neurosciences (CAN-ACN), held in Montreal, May 25-28.

The neurotransmitter glutamate has long been known to promote cell death, and its toxic effects occur through the action of a family of receptors known as the NMDARs (N-methyl-D-Aspartate ionotropic glutamate receptors). Unfortunately, treating disorders of the nervous system by blocking NMDARs has not been successful because such treatments have numerous side effects. A recent hypothesis based on work from many scientists suggests that NMDARs located in different regions at the surface of neurons may have opposite effects, which would explain why blocking all NMDARs is not a good treatment option. A synapse is a structure that allows one neuron to connect to another neuron and pass an electrical or chemical signal between them. Many receptors for neurotransmitters are located in synapses, as these are the main area where these chemical signals are transmitted. However, receptors can also be found outside the synapse, and in this case are called extra-synaptic receptors. Many recent studies have revealed that NMDARs located at synapses act to increase survival signaling and promote learning and memory, whereas extra-synaptic NMDARs shut off survival signaling, interfere with learning mechanisms, and increase cell death pathways.

Dr. Raymond and her team were able, by using a drug that selectively blocks extra-synaptic NMDARs early, before the appearance of any symptoms, to delay the onset of Huntington-like symptoms in a mouse model of the disease. These promising results could lead to new treatment avenues for Huntington patients, and delay the appearance of symptoms. "The drug we used, memantine, is currently being used to treat moderate-stage Alzheimer disease patients. Our results suggest that clinical studies of memantine and similarly-acting drugs in Huntington disease, particularly in the pre-symptomatic stage, are warranted,"says Dr. Raymond.

Extra-synaptic NMDARs have also been shown to be involved in other neurodegenerative diseases, such as Alzheimer disease, and in damage caused by traumatic brain injury and some forms of stroke. These results therefore suggest novel treatment avenues for many conditions in which neurons degenerate and die, a new way to protect neurons before the appearance of symptoms of neurodegeneration.

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The above story is based on materials provided by Canadian Association for Neuroscience. Note: Materials may be edited for content and length.

Refugees struggling to access cancer treatment, experts warn

May 25 / 2014

The Lancet

There is a high demand for costly cancer treatment among refugees from the recent conflicts in Iraq and Syria, with host countries struggling to find the money and the medicine to treat their new patients, new research concludes. The findings have prompted calls from the United Nations High Commissioner for Refugees (UNHCR) Chief Medical Expert, for innovative financing schemes to improve access to affordable high-quality cancer care for refugees.

A study published in The Lancet Oncology journal reveals a high demand for costly cancer treatment among refugees from the recent conflicts in Iraq and Syria, with host countries struggling to find the money and the medicine to treat their new patients. The findings have prompted calls from lead author Dr Paul Spiegel, the United Nations High Commissioner for Refugees (UNHCR) Chief Medical Expert, for innovative financing schemes to improve access to affordable high-quality cancer care for refugees.

In the first study of its kind, Spiegel and colleagues examined data from funding applications made to the UNHCR Exceptional Care Committee (ECC) from refugees in Jordan and Syria whose cancer treatment costs were likely to exceed US$2000 a year.

The findings show that cancer is an important public health problem in refugee settings and highlight the huge challenges and immense costs that national health systems and humanitarian organizations face when overwhelmed by massive influxes of refugees.

For example, in Jordan the ECC assessed 1989 applications for treatment between 2010 and 2012, of which roughly a quarter (511) were for cancer -- breast cancer and colorectal cancer being the most common. Around half (48%) of these cases were approved and funded. The main reasons for denied funding were a poor prognosis (43% of cases in 2011 and 31% in 2012) or that the treatment was too costly (25% in 2011). The average amount requested from the ECC for cancer treatment was US$11 540 in 2011 and US$5151 in 2012; however, the amounts approved were substantially lower -- US$4626 in 2011 and US$3501 in 2012.

"The countries in the Middle East have welcomed millions of refugees, first from Iraq and then Syria. This massive influx has strained health systems at all levels. Despite help from international organizations and donors to expand health facilities and pay for additional personnel and drugs, it has been insufficient. The burden has fallen disproportionately on the host countries to absorb the costs. For example, the Jordanian Ministry of Health footed an estimated $53 million bill for medical care for refugees in the first four months of 2013," says Dr Spiegel.

The authors call for improved cancer prevention and treatment in refugee settings through the use of innovative financing schemes, better primary care including screening for common cancers (eg, colonoscopies and mammograms), and the development of electronic web-based cancer registries to prevent interruption of treatment.

According to Dr Spiegel, "Until now, the response to humanitarian crises have been primarily based on experiences from refugee camps in sub-Saharan Africa where infectious diseases and malnutrition have been the priority. In the 21^st century, refugee situations are substantially longer and increasingly occur in middle-income countries where the levels of chronic diseases, including cancer, are higher. Cancer diagnosis and care in humanitarian emergencies typifies a growing trend towards more costly chronic disease care, something that seems to have been overlooked, but is of increasing importance because the number of refugees is growing."

Story Source:

The above story is based on materials provided by The Lancet. Note: Materials may be edited for content and length.

Journal Reference:

Paul Spiegel, Adam Khalifa, Farrah J Mateen. Cancer in refugees in Jordan and Syria between 2009 and 2012: challenges and the way forward in humanitarian emergencies. The Lancet Oncology, 2014; 15 (7): e290 DOI: 10.1016/S1470-2045(14)70067-1

Cancer immunotherapy: Potential new target found

Scientists have found a way to target elusive cells that suppress immune response, depleting them with peptides that spare other important cells and shrink tumors in preclinical experiments, according to a paper published online by Nature Medicine.

"We've known about these cells blocking immune response for a decade, but haven't been able to shut them down for lack of an identified target," said the paper's senior author, Larry Kwak, M.D., Ph.D., chair of Lymphoma/Myeloma and director of the Center for Cancer Immunology Research at The University of Texas MD Anderson Cancer Center.

The cells, called myeloid-derived suppressor cells (MDSCs), are found abundantly in the microenvironment around tumors. Created with other blood cells in the bone marrow, they interfere with activation and proliferation of T cells, the immune system's attack cells. MDSCs have been shown in mouse models to accelerate cancer progression and metastasis.

"This is the first demonstration of a molecule on these cells that allows us to make an antibody, in this case a peptide, to bind to them and get rid of them," Kwak said. "It's a brand new immunotherapy target."

Kwak has developed anti-cancer therapeutic vaccines to spark an immune system attack against tumors, but their effectiveness has been hindered by factors such as MDSCs that stifle immune response. "The key to taking cancer vaccines to another level is combining them with immunotherapies that target the tumor microenvironment," Kwak said.

Antibodies only bind to target cells Peptide antibodies developed by Kwak and co-discoverer, Hong Qin, Ph.D., assistant professor of Lymphoma/Myeloma, wipe out MDSCs in the blood, spleen and tumor cells of mice without binding to other white blood cells or dendritic cells involved in immune response.

"That's really exciting because it's so specific for MDSCs that we would expect few, if any, side effects," Kwak said. The team is working to develop the same target for use in humans.

With no candidate targets, the team took an objective approach by applying a peptide phage library to MDSCs, which permitted mass screening for candidate peptides -- short sequences of amino acids -- that bind to the surface of the MDSCs.

Peptide phage gathered from the MDSCs were expanded, enriched and then sequenced to identify predominant peptides. The team found two, labeled G3 and H6, that bound only to MDSCs; other candidates were eliminated because they also tied in to other types of cell.

They fused the two peptides to a portion of mouse immune globulin to generate experimental "peptibodies." Both peptibodies bound to both types of MDSC -- monocytic white blood cells, which engulf large foreign bodies or cell debris, and granulocytic white cells loaded with tiny granules.

The researchers treated mice with two types of thymus tumor with each peptibody, a control peptibody and an antibody against Gr-1. The G3 and H6 peptibodies depleted both types of MDSC in the blood and spleens of mice in both tumor models, while the Gr-1 antibody only worked against granulocytic MDSC.

Both peptibodies also wiped out the MDSCs in both types of thymic tumor and in the blood and spleen of mice with lymphoma.

Shrinking tumors, identifying alarmins To see whether MDSC depletion would impede tumor growth, they treated mice with thymic tumors with the peptides every other day for two weeks. Mice treated with either pep-G3 or pep-H6 had tumors that were about half the size and weight of those in mice treated with controls or the Gr-1 antibody.

Analysis of surface proteins on the MDSCs identified S100A9 and S100A8 as the likely binding targets for the two peptibodies. They're members of the S100 family of proteins, called alarmins, which are released outside the cell as a danger signal in response to inflammation.

MDSCs' mechanisms for blocking immune response are not well-characterized because they've been hard to study for lack of a targeting method, Kwak said.

Kwak and colleagues are working to extend their findings to human MDSCs.

A new class of drugs called immune checkpoint inhibitors block molecules on T cells that shut down immune response, freeing the immune system to attack tumors. The first of these drugs, ipilimumab (Yervoy®) was approved by federal regulators to treat advanced melanoma. It's the only drug ever to lengthen survival for those patients. Additional immune checkpoint inhibitors are under development.

"Immune checkpoint blockade is great," Kwak said. "There have been dramatic response rates, but those drugs also have side effects. Targeting MDSCs could provide an additional way to unleash the immune system."

Story Source:

The above story is based on materials provided by University of Texas M. D. Anderson Cancer Center. Note: Materials may be edited for content and length.

Journal Reference:

Hong Qin, Beatrisa Lerman, Ippei Sakamaki, Guowei Wei, Soungchul C Cha, Sheetal S Rao, Jianfei Qian, Yared Hailemichael, Roza Nurieva, Karen C Dwyer, Johannes Roth, Qing Yi, Willem W Overwijk, Larry W Kwak. Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice. Nature Medicine, 2014; DOI: 10.1038/nm.3560

How signals trigger cancer cells to spread

Click to enlarge

This electron micrograph shows a cancer cell (upper darker area) that has formed three invadopodia that are penetrating the adjacent extracellular matrix (lower lighter area).

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered a signaling pathway in cancer cells that controls their ability to invade nearby tissues in a finely orchestrated manner. The findings offer insights into the early molecular events involved in metastasis, the deadly spread of cancer cells from primary tumor to other parts of the body. The study was published today in the online edition of Nature Cell Biology.

To migrate from a primary tumor, a cancer cell must first break through surrounding connective tissue known as the extracellular matrix (ECM). The cancer cell does so by forming short-lived invadopodia--foot-like protrusions these cells use to invade. Invadopodia release enzymes that degrade the ECM, while other protrusions pull the cancer cell along, much like a locomotive pulls a train. The invading cancer cell relies on the cycle of invadopodium formation/disappearance to successfully travel from the tumor and enter nearby blood vessels to be carried to distant parts of the body.

"We've known for some time that invadopodia are driven by protein filaments called actin," said study leader Louis Hodgson, Ph.D., assistant professor of anatomy and structural biology at Einstein. "But exactly what was regulating the actin in invadopodia was not clear."

Previous studies had suggested that a protein called Rac1 played a role in cancer-cell invasion. When Rac1 levels are elevated, cancer cells display more invasive characteristics. But this suspected Rac1 activity in invadopodia had never been directly observed, only indirectly inferred.

To surmount this hurdle, Dr. Hodgson and his colleagues in the Gruss Lipper Biophotonics Center at Einstein devised a new fluorescent protein biosensor that, combined with live-cell imaging, revealed exactly when and where Rac1 is activated inside cancer cells.

Using this biosensor in highly invasive breast cancer cells taken from rodents and humans, the Einstein team discovered that when an individual invadopodium forms and is actively degrading the ECM, its Rac1 levels are low; on the other hand, elevated Rac1 levels coincide with the invadopodium's disappearance. "So high levels of Rac1 induce the disappearance of ECM-degrading invadopodia, while low levels allow them to stay -- which is the complete opposite of what Rac1 was thought to be doing in invadopodia," said Dr. Hodgson.

To confirm this observation, the researchers used siRNAs (molecules that silence gene expression) to turn off the RAC1 gene, which synthesizes Rac1 protein. When the gene was silenced, ECM degradation increased. Conversely, when Rac1 activity was enhanced -- using light to activate a form of the Rac1 protein -- the invadopodia disappeared.

In subsequent experiments, the Einstein team deciphered other parts of the Rac1 signaling cascade during invasion and showed that this signaling mechanism is regulated differently in normal breast epithelial cells.

"Rac1 levels in invadopodia of invasive tumor cells appear to surge and ebb at precisely timed intervals in order to maximize the cells' invasive capabilities," said Dr. Hodgson.

Most of the 580,000 U.S. cancer deaths each year are caused by complications from the spread of cancer to distant tissues and organs, rather than from the primary tumor itself. So throwing a monkey wrench into the inner workings of invasive tumor cells -- perhaps with a drug that prevents them from locally activating or inhibiting Rac1 -- could be extremely useful.

"Rac1 inhibitors have been developed," Dr. Hodgson said, "but it wouldn't be safe to use them indiscriminately. Rac1 is an important molecule in healthy cells, including immune cells. So we'd need to find a way to shut off this signaling pathway specifically in cancer cells."

Story Source:

The above story is based on materials provided by Albert Einstein College of Medicine of Yeshiva University. Note: Materials may be edited for content and length.

Journal Reference:

Yasmin Moshfegh, Jose Javier Bravo-Cordero, Veronika Miskolci, John Condeelis, Louis Hodgson. A Trio–Rac1–Pak1 signalling axis drives invadopodia disassembly. Nature Cell Biology, 2014; DOI: 10.1038/ncb2972

Brain imaging reveals clues about chronic fatigue syndrome

May 23 /2014

Emory Health Sciences

A brain imaging study showed differences in the basal ganglia when chronic fatigue syndrome patients (CFS) vs. healthy controls played a card game. The findings suggest that chronic fatigue syndrome is associated with changes in the brain involving brain circuits that regulate motor activity and motivation. This reduction of basal ganglia activity was also linked with the severity of fatigue symptoms.

A brain imaging study shows that patients with chronic fatigue syndrome may have reduced responses, compared with healthy controls, in a region of the brain connected with fatigue. The findings suggest that chronic fatigue syndrome is associated with changes in the brain involving brain circuits that regulate motor activity and motivation.

Compared with healthy controls, patients with chronic fatigue syndrome had less activation of the basal ganglia, as measured by fMRI (functional magnetic resonance imaging). This reduction of basal ganglia activity was also linked with the severity of fatigue symptoms.

According to the Centers for Disease Control and Prevention, chronic fatigue syndrome is a debilitating and complex disorder characterized by intense fatigue that is not improved by bed rest and that may be worsened by exercise or mental stress.

The results are scheduled for publication in the journal PLOS One.

"We chose the basal ganglia because they are primary targets of inflammation in the brain," says lead author Andrew Miller, MD. "Results from a number of previous studies suggest that increased inflammation may be a contributing factor to fatigue in CFS patients, and may even be the cause in some patients."

Miller is William P. Timmie professor of psychiatry and behavioral sciences at Emory University School of Medicine. The study was a collaboration among researchers at Emory University School of Medicine, the CDC's Chronic Viral Diseases Branch, and the University of Modena and Reggio Emilia in Italy. The study was funded by the CDC.

The basal ganglia are structures deep within the brain, thought to be responsible for control of movements and responses to rewards as well as cognitive functions. Several neurological disorders involve dysfunction of the basal ganglia, including Parkinson's disease and Huntington's disease, for example.

In previous published studies by Emory researchers, people taking interferon alpha as a treatment for hepatitis C, which can induce severe fatigue, also show reduced activity in the basal ganglia. Interferon alpha is a protein naturally produced by the body, as part of the inflammatory response to viral infection. Inflammation has also been linked to fatigue in other groups such as breast cancer survivors.

"A number of previous studies have suggested that responses to viruses may underlie some cases of CFS," Miller says. "Our data supports the idea that the body's immune response to viruses could be associated with fatigue by affecting the brain through inflammation. We are continuing to study how inflammation affects the basal ganglia and what effects that has on other brain regions and brain function. These future studies could help inform new treatments."

Treatment implications might include the potential utility of medications to alter the body's immune response by blocking inflammation, or providing drugs that enhance basal ganglia function, he says.

The researchers compared 18 patients diagnosed with chronic fatigue syndrome with 41 healthy volunteers. The 18 patients were recruited [not referred] based on an initial telephone survey followed by extensive clinical evaluations. The clinical evaluations, which came in two phases, were completed by hundreds of Georgia residents. People with major depression or who were taking antidepressants were excluded from the imaging study, although those with anxiety disorders were not.

For the brain imaging portion of the study, participants were told they'd win a dollar if they correctly guessed whether a preselected card was red or black. After they made a guess, the color of the card was revealed, and at that point researchers measured blood flow to the basal ganglia.

The key measurement was: how big is the difference in activity between a win or a loss? Participants' scores on a survey gauging their levels of fatigue were tied to the difference in basal ganglia activity between winning and losing. Those with the most fatigue had the smallest changes, especially in the right caudate and the right globus pallidus, both parts of the basal ganglia.

Ongoing studies at Emory are further investigating the impact of inflammation on the basal ganglia, including studies using anti-inflammatory treatments to reduce fatigue and loss of motivation in patients with depression and other disorders with inflammation including cancer.

Story Source:

The above story is based on materials provided by Emory Health Sciences. Note: Materials may be edited for content and length.

The digital film reel

Instead of heavy rolls of film, digital film copies are sent to movie theaters these days. With the easyDCP software, these digital packages can be easily created in the required standard so that the digital film can run in any theater.

For more than a hundred years, analog technology dominated the cinema. Moving pictures were captured on film made from celluloid or polyester, and uniform standards applied worldwide. Each film strip was 35 millimeters wide and perforated along the outside edges. This way, it could be shown in any theater. Distribution of digital movies has changed all that: instead of sending analog reels of film, movie theaters receive DCPs (Digital Cinema Packages) via hard drive or satellite that include not only the encoded digital video and audio data but also subtitles in multiple languages.

Digital cinema needs universal standards too. Only then can digital films be shown in any cinema worldwide; In 2005, the six largest Hollywood studios defined the DCI standards, the technical specifications for digital cinema. At the studios' request, researchers at the Fraunhofer Institute for Integrated Circuits IIS in Erlangen have created international test procedures for compliance with the specifications of the DCI standards. In order to ensure that digital film copies meet these standards, the experts at Fraunhofer IIS have developed a software for creating DCPs suitable for all playback devices that work reliably on all cinema systems.

Simple and clear operation

"While developing easyDCP, we really concentrated on keeping operation simple and clear," says Dr. Siegfried Foessel, director of the Moving Picture Technologies department at Fraunhofer IIS. That's a concept that users found persuasive. In very little time easyDCP became the market leader; more than 1000 customers already use the software. Meanwhile large companies have started integrating easyDCP software into their products including Quantel, Drastic, and Blackmagic Design.

"We've tested easyDCP-created cinema packages on any number of playback devices and continuously improved the software," explains Heiko Sparenberg, head of the Digital Cinema group at Fraunhofer IIS. As for why the software has established itself so successfully on the market, "Feedback from our users has played an important role," he explains. The software enables not only the largest studios, but also smaller, independent producers and film makers to create their own digital cinema packages. Post-production companies, film producers, distributors and film festivals -- all profit from the comprehensive software functions, such as the adding of subtitles and audio tracks in different languages or the support of 3D formats or 4K resolution. At the Berlin International Film Festival, the software is used to test the quality of digital film copies from around the world, so that flawed cinema packages can be quickly identified andprepared and validated for proper screening.

For their work on the topic "Digital cinema conquers the world -- software for creating digital cinema packages enables digital cinema's breakthrough" Dipl.-Inf. Heiko Sparenberg and Dr.-Ing. Siegfried Foessel received this year's Joseph von Fraunhofer Prize.

Story Source:

The above story is based on materials provided by Fraunhofer-Gesellschaft. Note: Materials may be edited for content and length.

Inspecting letters with terahertz waves

Is it a harmless parcel or a bomb, an innocent letter or a drug shipment? A new terahertz scanner is capable of detecting illicit drugs and explosives sent by post without having to open suspicious packages or envelopes.

Alert at Schloss Bellevue. A suspicious letter addressed to German President Joachim Gauck has been detected, which might contain a bomb. Not willing to take any risks, the bomb squad is called out to destroy the package. Later investigations revealed that the envelope did not contain any explosives, but better safe than sorry. A year ago, this event created turmoil in the mail sorting office in Berlin, because at the time there was no safe and simple way of reliably detecting the presence of explosives or drugs in letters and small packets.

A new solution is offered by the terahertz scanner developed by researchers at the Fraunhofer Institute for Physical Measurement Techniques IPM in Kaiserslautern in collaboration with Hübner GmbH & Co. KG in Kassel. Their T-COGNITION system is capable of detecting and identifying the hidden content of suspicious packages or envelopes without having to open them. One of this year's Joseph von Fraunhofer prizes was awarded to Prof. Dr. René Beigang of Fraunhofer IPM and Dipl.-Ing. Thorsten Sprenger, Head of Public Security and Photonics at Hübner, for their work on the terahertz scanner for the secure identification of hazardous materials and illicit drugs in postal consignments.

But why did the scientists choose to use terahertz waves for this application? Professor René Beigang explains: "The terahertz range lies midway between microwave and infrared in the electromagnetic spectrum, and thus combines the advantages of both." Like microwaves, these low-energy frequencies can easily penetrate paper, wood, lightweight fabrics, plastics, and ceramics. Moreover, terahertz waves generate characteristic spectra depending on the type of material they travel through, which can be analyzed quickly using intelligent software. A further significant advantage is that terahertz waves are non-ionizing and therefore safe to use in an unprotected environment, unlike X-rays. This makes the technology an interesting option for use in mail scanners.

Scaling up terahertz technology for industrial applications

Terahertz technology is still in its infancy, and until now it has found relatively few applications. The department of Material Characterization and Testing at the University of Kaiserslautern, sponsored jointly by Fraunhofer IPM and the Land of Rheinland-Pfalz, hopes to change this situation. "Our goal is to scale up terahertz technology and extend its range of use to include security applications," says Beigang. The engineers at Hübner were among the first to recognize the potential of the Fraunhofer researchers' work. The company's traditional line of business is manufacturing key components for the transportation industry (e.g. rail vehicles, buses, airport technology, automotive). A new division for public security was added in 2006, when the company first started to look for cooperation partners. The mail scanner project was launched four years later, based on previous joint development projects. In the meantime, the company has brought its T-COGNITION solution onto the market.

This is how the mail scanner works. Suspicious envelopes and packages are fed into the scanner on a retractable tray. They are then exposed to terahertz waves which are absorbed at different frequencies within the spectral range depending on the substance they travel through (characteristic absorption properties). Detectors at the output of the scanner record the transmitted wavelengths. "Within a few seconds, T-COGNITION produces a spectroscopic fingerprint that allows the detected hazardous material to be compared with database samples and definitively identified," says Thorsten Sprenger.

The system triggers an alarm if the consignment contains explosives or illicit drugs.The system is capable of examining the content of postal items up to C4 format with a thickness of up to two centimeters. Sprenger says: "It is the ideal mailroom solution for prisons, customs offices, government agencies, company headquarters, and embassies or consulates, because it helps to improve security and protect human lives."

Story Source:

The above story is based on materials provided by Fraunhofer-Gesellschaft. Note: Materials may be edited for content and length.

Thefix roundup

Morning roundup- from thefix.com

Immune system precursor cells that fight infection discovered

May 26 / 2014

Universität Mainz

The innate immune system recognizes infectious agents such as viruses and bacteria. A group of lymphocytes known as "innate lymphoid cells" or ILCs plays a central role in the defense of the human body against infective agents, researchers have found. They have discovered previously unidentified ILCs that are able to protect epithelial surfaces, such as those of the intestinal mucosa, against infection. The results provide important additional insights into how the immune system functions.

Professor Andreas Diefenbach of the Research Center Immunology at the Mainz University Medical Center, working in collaboration with scientists at the University of Freiburg, has discovered previously unidentified ILCs that are able to protect epithelial surfaces, such as those of the intestinal mucosa, against infection. The results provide important additional insights into how the immune system functions. It is also possible that these findings, recently published in the international journal Cell, could result in the development of new vaccination strategies that would prevent intracellular infections.

ILCs are among the most important weapons of the innate immune system and help it to fight infections and prevent the development of cancer. However, ILCs are not only of critical importance when it comes to preventing infections. They also have important functions in non-immunological processes, such as organ homeostasis, i.e., the maintenance of the physiological functional status of vital organs. Professor Andreas Diefenbach, Director of the Department of Medical Microbiology and Hygiene at the Mainz University Medical Center, has now identified a previously unrecognized ILC population. Specifically, he has been able to identify previously unknown precursor cells from which all types of ILCs may originate and to describe a new ILC subgroup called type 1 ILCs.

"The fact that we have found the potential precursor cell for all ILCs has opened up completely new horizons for research in the field of immunology. We now have a realistic chance of identifying the signals controlling differentiation of such precursor cells into each of the various ILC types," said Diefenbach. "If we understand how distinct types of ILCs are involved in the development of inflammatory bowel diseases and autoimmune disorders, we may be able to precisely suppress this unwanted programming of ILCs in the future." Diefenbach succeeded in detecting the unknown ILCs and the precursor cell at the molecular genetic level with the aid of fluorescent proteins.

"A healthy immune system is the key to preventing illnesses. So it is all the more important for us to obtain a comprehensive understanding of how the immune system operates. With this discovery, Professor Andreas Diefenbach and his team have made additional important progress in understanding the immune system in all its facets," stated the Chief Scientific Officer of the Mainz University Medical Center, Professor Ulrich Förstermann.

Story Source:

The above story is based on materials provided by Universität Mainz. Note: Materials may be edited for content and length.

Journal Reference:

Christoph S.N. Klose, Melanie Flach, Luisa Möhle, Leif Rogell, Thomas Hoyler, Karolina Ebert, Carola Fabiunke, Dietmar Pfeifer, Veronika Sexl, Diogo Fonseca-Pereira, Rita G. Domingues, Henrique Veiga-Fernandes, Sebastian J. Arnold, Meinrad Busslinger, Ildiko R. Dunay, Yakup Tanriver, Andreas Diefenbach. Differentiation of Type 1 ILCs from a Common Progenitor to All Helper-like Innate Lymphoid Cell Lineages. Cell, 2014; 157 (2): 340 DOI: 10.1016/j.cell.2014.03.030

Novel drug target linked to insulin secretion, type 2 diabetes treatment found

May 26 / 2014

Universite de Montreal

A signal that promotes insulin secretion and reduces hyperglycemia in a type 2 diabetes animal model is enhanced by the inhibition of a novel enzyme recently discovered researchers. Insulin is an important hormone in our body that controls glucose and fat utilization. Insufficient insulin release by the beta-cells of the pancreas and interference with the action of insulin lead to type 2 diabetes. The secretion in the blood of insulin is dependent upon the utilization of glucose and fat by the beta-cells and the production of a novel signal that they discovered named monoacylglycerol.

A signal that promotes insulin secretion and reduces hyperglycemia in a type 2 diabetes animal model is enhanced by the inhibition of a novel enzyme discovered by CHUM Research Centre (CRCHUM) and University of Montreal researchers. The team is part of the Montreal Diabetes Research Center and their study, published recently in Cell Metabolism, was directed by researchers Marc Prentki and Murthy Madiraju.

Insulin is an important hormone in our body that controls glucose and fat utilization. Insufficient insulin release by the beta-cells of the pancreas and interference with the action of insulin lead to type 2 diabetes. The secretion in the blood of insulin is dependent upon the utilization of glucose and fat by the beta-cells and the production of a novel signal that they discovered named monoacylglycerol.

"Despite significant research on the mechanisms implicated in insulin secretion, the signal molecules involved in this process remained enigmatic; the identification of these signals is necessary to develop better therapeutics against diabetes," explains Marc Prentki, Director of the Montreal Diabetes Research Centre and Professor at the University of Montreal. Marc Prentki holds the Canada Research Chair in Diabetes and Metabolism.

"When sugar is being used by the insulin secreting pancreatic beta-cell, it produces monoacylglycerol, a fat-like signal and this is associated with insulin release into blood; we found that the production of monoacylglycerol is essential for glucose-stimulated insulin secretion by the beta-cell," says Murthy Madiraju, Researcher at the CRCHUM. Importantly, the research team discovered that an enzyme called alpha/beta hydrolase domain-6 (in short ABHD6) breaks down monoacylglycerol and thus negatively controls insulin release.

These researchers said that "an ideal drug for type-2 diabetes would increase insulin levels in blood by enhancing the beta cells response to glucose only when it is elevated and also increase the sensitivity of body tissues to insulin; this is precisely what ABHD6 inhibition does and thus we have identified a unique new target for type 2 diabetes."

Story Source:

The above story is based on materials provided by Universite de Montreal. Note: Materials may be edited for content and length.

Journal Reference:

Shangang Zhao, Yves Mugabo, Jose Iglesias, Li Xie, Viviane Delghingaro-Augusto, Roxane Lussier, Marie-Line Peyot, Erik Joly, Bouchra Taïb, Matthew A. Davis, J. Mark Brown, Abdelkarim Abousalham, Herbert Gaisano, S.R. Murthy Madiraju, Marc Prentki. α/β-Hydrolase Domain-6-Accessible Monoacylglycerol Controls Glucose-Stimulated Insulin Secretion. Cell Metabolism, 2014; DOI: 10.1016/j.cmet.2014.04.003

Immunotherapy for prostate cancer in sight

An international study carried out with involvement of the MedUni Vienna is giving hope to patients with advanced prostate cancer. In just a few years' time, Ipilumumab could be approved as a treatment for the world's third-most common type of cancer.

The immunotherapeutic agent Ipilumumab has been shown to have a markedly positive effect in the treatment of patients who are resistant to conventional hormone treatments and chemotherapy. These are the words of a core statement from a study, recently published in the journal The Lancet Oncology, which was set up based on collaboration between the world's leading centres for the research and treatment of prostate cancer.

The scientists investigated the extent to which immunotherapy with this agent is also suitable for the more common type of advanced prostate cancer. The medication is already being successfully used as immunotherapy for advanced melanoma -- a comparatively rare type of cancer.

Major success in the immunotherapy of carcinomas

Michael Krainer, Head of the Urological Tumours Working Group within the Department of Oncology (University Department of Internal Medicine I) at the MedUni Vienna, which played a key role as the lead recruitment centre for Germany and Austria, had this to say about the study results: "For us, it is virtually a miracle that immunotherapy demonstrates such a clear effect at such a late stage of the disease. The results of our study must be regarded as a further major success in the immunotherapy of carcinomas." The substance's mechanism of action is as follows: the Ipilumumab antibodies disable "inhibitors," giving the body's immune system a boost.

Approval of the medication in sight

Despite this good effect, it's not all plain sailing: the "revved up" immune system can also attack the body's own tissues. According to the study, Ipilumumab is therefore not suitable -- in view of its side effects -- for treating patients with advanced prostate cancer who are in poor general health. For this reason, a further study is currently underway and is expected to be completed in 2015. This follow-on study is limited to patients with a better prognosis and who are in better overall health. Krainer expresses his expectations thus: "Based on our results, I anticipate that this study will bring approval for Ipilumumab for patients with advanced prostate cancer."

European Centre of Expertise for urological tumours

The Urological Tumours Working Group at the MedUni Vienna is regarded across Europe as one of the most highly respected study support centres in the field of prostate cancer. Since 2002, several hundred patients have been included in 17 clinical studies. The spectrum covers all modern treatment options and ranges from chemotherapy and hormone therapy to immunotherapy.

Prostate cancer: the third-most common form of cancer

Worldwide, prostate cancer is the third-most common form of cancer and is globally the sixth-most common cause of death from cancer among men. Each year, around 300,000 men are diagnosed with the condition within the European Union, and around two million men in the EU are currently living with the condition.

Story Source:

The above story is based on materials provided by Medical University of Vienna. Note: Materials may be edited for content and length.

Journal Reference:

Eugene D Kwon, Charles G Drake, Howard I Scher, Karim Fizazi, Alberto Bossi, Alfons J M van den Eertwegh, Michael Krainer, Nadine Houede, Ricardo Santos, Hakim Mahammedi, Siobhan Ng, Michele Maio, Fabio A Franke, Santhanam Sundar, Neeraj Agarwal, Andries M Bergman, Tudor E Ciuleanu, Ernesto Korbenfeld, Lisa Sengeløv, Steinbjorn Hansen, Christopher Logothetis, Tomasz M Beer, M Brent McHenry, Paul Gagnier, David Liu, Winald R Gerritsen. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. The Lancet Oncology, 2014; 15 (7): 700 DOI: 10.1016/S1470-2045(14)70189-5

A new solution for storing hydrogen fuel for alternative energy

Turning the "hydrogen economy" concept into a reality, even on a small scale, has been a bumpy road, but scientists are developing a novel way to store hydrogen to smooth out the long-awaited transition away from fossil fuels. Their report on a new solid, stable material that can pack in a large amount of hydrogen that can be used as a fuel appears in the ACS journal Chemistry of Materials.

Umit B. Demirci and colleagues explain that storing hydrogen in solids is a recent development and a promising step toward building a hydrogen economy. That's the idea originated in the 1970s and promoted by former President George W. Bush that we replace fossil fuels with hydrogen, which can serve as a clean fuel. Although a promising alternative to conventional energy sources, hydrogen has posed a number of technological challenges that scientists are still overcoming. One of those issues has to do with storage. Previously, researchers were focused on developing hydrogen-containing liquids or compressing it in gas form. Now, solid storage is showing potential for holding hydrogen in a safe, stable and efficient way. In the latest development on this front, Demirci's team looked to a new kind of material.

They figured out a way to make a novel crystal phase of a material containing lithium, boron and the key ingredient, hydrogen. To check how they could get the hydrogen back out of the material, the scientists heated it and found that it released hydrogen easily, quickly and only traces of unwanted by-products.

Story Source:

The above story is based on materials provided by American Chemical Society. Note: Materials may be edited for content and length.

Journal Reference:

Romain Moury, Umit B. Demirci, Voraksmy Ban, Yaroslav Filinchuk, Takayuki Ichikawa, Liang Zeng, Kiyotaka Goshome, Philippe Miele. Lithium Hydrazinidoborane: A Polymorphic Material with Potential for Chemical Hydrogen Storage. Chemistry of Materials, 2014; 140515111242000 DOI: 10.1021/cm500980b

Fighting cancer with dietary changes

May 26 / 2014

Thomas Jefferson University

Calorie restriction during treatment for breast cancer changes cellular programming in a way that lowers the chance of metastases in mice. Breast cancer patients are often treated with hormonal therapy to block tumor growth, and steroids to counteract the side effects of chemotherapy. However, both treatments can cause a patient to have altered metabolism which can lead to weight gain. In fact, women gain an average of 10 pounds in their first year of treatment. Recent studies have shown that too much weight makes standard treatments for breast cancer less effective, and those who gain weight during treatment have worse cancer outcomes.

Calorie restriction, a kind of dieting in which food intake is decreased by a certain percentage, has been touted as way to help people live longer. New research suggests that there may be other benefits, including improving outcomes for women in breast cancer. According to a study published May 26th in Breast Cancer Research and Treatment, the triple negative subtype of breast cancer -- one of the most aggressive forms -- is less likely to spread, or metastasize, to new sites in the body when mice were fed a restricted diet.

"The diet turned on a epigenetic program that protected mice from metastatic disease," says senior author Nicole Simone, M.D., an associate professor in the department of Radiation Oncology at Thomas Jefferson University. Indeed, when mouse models of triple negative cancer were fed 30 percent less than what they ate when given free access to food, the cancer cells decreased their production of microRNAs 17 and 20 (miR 17/20). Researchers have found that this group of miRs is often increased in triple negative cancers that metastasize.

Breast cancer patients are often treated with hormonal therapy to block tumor growth, and steroids to counteract the side effects of chemotherapy. However, both treatments can cause a patient to have altered metabolism which can lead to weight gain. In fact, women gain an average of 10 pounds in their first year of treatment. Recent studies have shown that too much weight makes standard treatments for breast cancer less effective, and those who gain weight during treatment have worse cancer outcomes. "That's why it's important to look at metabolism when treating women with cancer," says Dr. Simone.

In earlier studies, Dr. Simone and colleagues had shown that calorie restriction boosted the tumor-killing effects of radiation therapy. This study aimed to examine which molecular pathways were involved in this cooperative effect.

The investigators noticed that microRNAs -- a type of RNA that regulates other genes in the cell -- specifically miR 17 and 20, decreased the most when mice were treated with both radiation and calorie restriction. This decrease in turn increased the production of proteins involved in maintaining the extracellular matrix. "Calorie restriction promotes epigenetic changes in the breast tissue that keep the extracellular matrix strong," says Dr. Simone. "A strong matrix creates a sort of cage around the tumor, making it more difficult for cancer cells to escape and spread to new sites in the body."

Understanding the link to miR 17 also gives researchers a molecular target for diagnosing cancers that are more likely to metastasize and, potentially, for developing a new drug to treat the cancers. In theory, a drug that decreased miR 17 could have the same effect on the extracellular matrix as calorie restriction. However, targeting a single molecular pathway, such as the miR17 is unlikely to be as effective as calorie restriction, says Dr. Simone. Triple negative breast cancers tend to be quite different genetically from patient to patient. If calorie restriction is as effective in women as it is in animal models, then it would likely change the expression patterns of a large set of genes, hitting multiple targets at once without toxicity.

In order to test that this hypothesis is true in humans, Dr. Simone is currently enrolling patients in the CaReFOR (Calorie Restriction for Oncology Research) trial. As the first trial like it in the country, women undergoing radiation therapy for breast cancer receive nutritional counseling and are guided through their weight loss plan as they undergo their treatment for breast cancer.

Story Source:

The above story is based on materials provided by Thomas Jefferson University. Note: Materials may be edited for content and length.

Journal Reference:

Lianjin Jin, Meng Lim, Shuping Zhao, Yuri Sano, Brittany A. Simone, Jason E. Savage, Eric Wickstrom, Kevin Camphausen, Richard G. Pestell, Nicole L. Simone. The metastatic potential of triple-negative breast cancer is decreased via caloric restriction-mediated reduction of the miR-17~92 cluster. Breast Cancer Research and Treatment, 2014; DOI: 10.1007/s10549-014-2978-7

Europe’s Landscape Is Still Scarred by World War I

(Michael St. Maur Sheil )

Ten thousand men were killed within seconds when the British exploded 19 mines under German lines during the Battle of Messines in Belgium. (Michael St. Maur Sheil )

100 years after the Battle of Verdun, its land—once a quiet stretch of French farmland—remains scarred from explosions. (Michael St. Maur Sheil)

On the Chemin des Dames, German soldiers took refuge in a former limestone quarry, which they called the Dragon’s Cavern. (Michael St. Maur Sheil)

Nearly 70 feet deep, the Lochnagar Crater was formed after an explosive-packed mine was detonated during the Battle of the Somme. (Michael St. Maur Sheil)

The tiny village of Butte de Vaquois once stood on a hilltop, and was destroyed after three years of furious mining blew away its summit. (Michael St. Maur Sheil)

A series of 12 bloody battles were fought between Austro-Hungrarian and Italian troops along the Isonzo River in Italy. (Michael St. Maur Sheil)