четверг, 26 мая 2011 г.

Proteins' 'Breaking Point' Found, UK

Scientists from Oxford University have discovered the watery secrets of what makes proteins unstable.

Their fundamental research into the 'critical condition' at which the biological function of proteins is destroyed could have a profound impact on many areas of science - including biology, materials science and medicine: In particular it could give fresh insights into diseases caused by proteins misfolding and how to mimic the properties of tissues such as cartilage and collagen.


The discovery comes from quantum mechanics simulations developed by Dr David Porter and Professor Fritz Vollrath of Oxford's Department of Zoology. 'The interaction of water with proteins is central to all biology, and the point at which water-protein interactions become unstable is arguably nature's most important 'critical condition',' said Dr David Porter. 'We can use these simulations to examine the physics and chemistry of hydrogen bonding between water and amide groups in a specific protein. The predictions from our models can then be translated into real biological stress conditions - of temperature, mechanical load and chemistry - that will cause this protein to become unstable and stop functioning.'


The new research also sheds light on how the amount of water in a protein tissue affects its relative 'softness' and overall structural properties. Proteins with relatively little water will be stiff but tough - like a hard plastic - whereas a larger fraction of water (above 30 per cent) makes tissues such as elastin highly flexible and strong.


Dr Porter and Professor Vollrath originally created the simulations to try to understand how spiders 'tease' a normally stable protein solution into a solid silk thread using a combination of stress mechanisms; temperature, mechanical load and chemistry. 'It soon became clear that our silk model could be applied to many other protein stability problems,' said Professor Fritz Vollrath. 'A key innovation is that our models can map how instability develops over a time period of anything from a few seconds to a hundred years. Understanding the role of water in biological materials will be very important as we try to create new materials with predictable properties.'


The innovative use of new ways to extract critical conditions from their quantum simulations could have many other important applications in materials science: They could be used to predict the conditions under which materials will melt or move between an ordered and a less ordered state. Professor Vollrath said: 'Clearly we can learn much more from spider silk than how to make a tough material.'


Notes:


- A report of the research, 'The role of kinetics of water and amide bonding in protein instability', is published in a forthcoming issue of the RSC journal Soft Matter, an advance copy of the article is available online here.




Oxford University

News From The Journal Of The National Cancer Institute, Sept. 9 JNCI

Bias Correction of Familial Risk Estimates Increases Estimated Melanoma Risk But Not Risk of Other Common Cancers



The relative risk of familial melanoma increases substantially when researchers account for a known potential bias in a large cohort study. The relative risk of familial lung, breast, prostate, and colorectal cancer do not change substantially with the correction.



Researchers have used the Swedish Cancer Registry and the Swedish MultiGenerational Register to estimate the relative risk of cancers for individuals who have an affected first-degree relative. However, Kamila Czene, Ph.D., of the Karolinksa Institute and colleagues recently determined that such database analyses may underestimate the risk because cancers that occur before the start of registration are not included.



In the current study, Czene and colleagues adjusted for the bias by using data from a simulated population and applying that information to the Swedish cohort.



The relative risk of familial melanoma increased from 2.68 to 3.18 following the adjustment for the bias. The impact was even greater when an affected parent was diagnosed at a young age, increasing the relative risk to 4.07. The relative risks for colorectal, lung, breast, and prostate cancer remained close to 2.



"The lack of bias for most of these cancers is due to the relatively low familial risk…and/or relatively low incidence in the population, combined with a reasonably high sensitivity of the observed family history," the authors write. "Because sensitivity depends on age at onset, it is not surprising that the lowest sensitivity was observed for melanoma, a cancer with relatively young age at onset."



Experts Call for Renewed Efforts in Gastroenteropancreatic Neuroendocrine Tumors



During a September 2007 summit on neuroendocrine and carcinoid tumor, clinicians and researchers presented the current standards of care and identified key areas that require investigation and development.



Over the last 30 years, the incidence of these tumors has steadily increased in the United States, but there have been no substantial improvements in survival during that same time period.



At a National Cancer Institute-sponsored meeting, basic science and clinical researchers identified specific areas in the field that need to be addressed, which are summarized in a commentary by Irvin M. Modlin, M.D., Ph.D., D.Sc., of Yale University in New Haven, Conn., and colleagues. Those issues include increased public and physician education, identification of molecular markers for diagnosis and disease monitoring during therapy, standardization of pathology classifications, creation of regional centers of excellence, and improved in vitro and animal models of disease.
















"The group of experts at the meeting considered that the increasing incidence and prevalence of neuroendocrine disease in the United States was of considerable concern, particularly in light of the lack of evidence of improvement of outcome and the lack of any tangible evidence of the development of demonstrably effective novel therapies," the authors write.



Confirmation of Association with Chromosome 15 Locus and Familial Lung Cancer



Two single-nucleotide polymorphism (SNP) variants on the short arm of chromosome 15 appear to be associated with familial lung cancer.



Several research groups recently reported an association between the 15q24-25.1 locus and sporadic lung cancer risk.



To confirm that association with familial lung cancer, Ming You, M.D., Ph.D., of Washington University in St. Louis and colleagues performed a genome-wide association study using SNPs on 194 case patients with familial lung cancer and 219 cancer-free individuals.



You and colleagues found a strong association between the 15q24-25.1 locus and familial lung cancer. Two SNP variants were associated with the risk of lung cancer, although the identity of a causal gene was not identified.



"Determination of a likely single candidate gene and further delineation of whether variants affect lung cancer directly or indirectly or both are warranted," the authors conclude.



Also in the September 9 JNCI:
Evaluation Of Quality Measure For Colon Cancer Care Suggests Considerable Improvements Needed


5- And 10-Year Survival Continues To Improve For US Children With Hematologic Malignancies


India: Breast Cancer Screening May Lower Mortality And Disease Burden





The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Visit the Journal online at jnci.oxfordjournals/.



Source: Liz Savage


Journal of the National Cancer Institute

Launch Of Stem Cell Study For Acute Stroke Patients, UT Houston

A first-of-its-kind stem cell study to treat acute stroke victims is being launched by investigators at The University of Texas Medical School at Houston.



The Phase I study, funded with a pilot grant from The National Institutes of Health, will use the patients' own stem cells. Researchers will enroll 10 patients who have just suffered a stroke and are being treated in the Emergency Center at Memorial Hermann - Texas Medical Center. Physicians will obtain permission from the patient or patient's surrogate.



"This will be our first attempt to look at the safety of using stem cells in acute stroke patients," said Sean I. Savitz, M.D., assistant professor of neurology at the medical school. "There's a lot of promise behind this but we want to do it in a slow, rigorous fashion. Because we are injecting them intravenously, these cells can disperse to lots of different parts of the body and that's why we're looking at safety parameters."



Stroke occurs when blood flow to the brain is interrupted by a blockage or a rupture in an artery, depriving brain tissue of oxygen. It is the third-leading cause of death behind heart disease and cancer. According to the American Stroke Association, nearly 800,000 Americans suffer a stroke each year - one every 40 seconds. On average, someone dies of stroke every three to four minutes.



The stem cells will be harvested from the bone marrow in the iliac crest of the leg, then separated and returned to the patient within three to six hours. Because they are the patient's own stem cells, rejection is not expected to be an issue.



"This study is the critical first step in translating laboratory work with stem cells into benefit for patients. If effective, this treatment could be helpful to a huge segment of stroke patients to reduce their disability," said James C. Grotta, M.D., Roy M. and Phyllis Gough Huffington Distinguished Professor of Neurology and chair of the Department of Neurology at the medical school. "We are fortunate here at UT Houston and the Texas Medical Center to have the resources needed to carry out this work, and to have attracted someone of Dr. Savitz's caliber to lead this study."



The clinical study builds on laboratory and animal research indicating that stem cells from bone marrow can migrate to the injured area of the brain and help repair the damage.



"Animal studies have shown that when you administer stem cells after stroke, the cells enhance the healing. We know that stem cells have some kind of guidance system and migrate to the area of injury," Savitz said. "They're not making new brain cells but they may be enhancing the repair processes and reducing damage."



A UT Medical School study involving acute brain-injured children using their own stem cells has been underway since 2006 at Children's Memorial Hermann Hospital. Principal investigator of the study is Charles Cox, M.D., The Children's Fund, Inc. Distinguished Professor in Pediatric Surgery and Trauma at the medical school. Co-investigator is James Baumgartner, M.D., research collaborator with the medical school and a pediatric neurosurgeon at Children's Memorial Hermann Hospital.



"It's beneficial for this study that we have precedence. Dr. Cox and Dr. Baumgartner have been great in guiding me. That study has served as a model for us," Savitz said.







Enrollment will begin mid-February. The study is only open to patients who are admitted to the Emergency Center at Memorial Hermann - TMC with symptoms of an immediate stroke.



Source: Deborah Mann Lake


University of Texas Health Science Center at Houston

Structure Of Protein That Mutates DNA Of The AIDS Virus HIV-1determined By U Of M Researchers

Understanding the structure of proteins involved in inhibiting HIV-1 infection could help in the battle against AIDS, and University of Minnesota researchers have taken a crucial step in that direction.



Hiroshi Matsuo, Ph.D., and Reuben Harris, Ph.D., co-investigators of the research and assistant professors in the Department of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota have determined the structure of APOBEC3G - a protein that inhibits the AIDS virus, HIV. This discovery is the first to shed light on the atomic structure of the protein.



The research was released online Feb. 20, 2008 on the Nature Web site and it will be featured in an upcoming print publication of the journal.



Proteins could be compared to miniature machines, each of which carries out a specific function. The APOBEC3G "machine" is capable of modifying HIV DNA so that the virus is no longer infectious.



HIV-1, however, has unfortunately developed a way to evade this potent cellular protein with its own protein called Vif, which literally triggers the destruction of APOBEC3G.



The discovery will help researchers manipulate APOBEC3G to make it effective in combating HIV. Current studies also will help develop methods to neutralize Vif before it has a chance to destroy the protein.



"This new information is a crucial step toward understanding how APOBEC3G and Vif talk to each other," Harris said. "Furthermore this new information will undoubtedly help researchers identify candidate drugs for future novel HIV-1/AIDS therapies."







This research was funded by grants from the National Institutes of Health and from the Minnesota Partnership for Biotechnology and Medical Genomics and the Medica Foundation.



Source: Nick Hanson


University of Minnesota

Cost-Effective Technology For Disease Diagnosis And Biological Research Developed By Singapore Scientists

A novel electronic sensor array for more rapid, accurate and cost-efficient testing of DNA for disease diagnosis and biological research has been developed by scientists at Singapore's Institute of Bioengineering and Nanotechnology (IBN).



In a recent Journal of the American Chemical Society, IBN scientists reported that based on laboratory results, their Nanogap Sensor Array has shown "excellent" sensitivity at detecting trace amounts of DNA.



"By saving time and lowering expenses, our newly developed Nanogap Sensor Array offers a scalable and viable alternative for DNA testing," said Zhiqiang Gao, Ph.D., Group Leader at IBN, the world's first bioengineering and nanotechnology research institute.



The biosensor translates the presence of DNA into an electrical signal for computer analysis. The distinctively designed sensor chip has the ability to detect DNA more efficiently by "sandwiching" the DNA strands between the two different surfaces.



"The novel vertical nanostructure design and two different surfaces of the sensor allow ultrasensitive detection of DNA," added Dr. Gao. "This sensitivity is best-in-class among electrical DNA biosensors. The design of the sensor also took into consideration the feasibility of mass production in a cost-effective way for expanded usage."



Conventionally, human DNA is detected through the use of polymerase chain reaction (PCR), which while effective, is also expensive, cumbersome and time-consuming for widespread use. The PCR technique amplifies a single piece of DNA across several orders of magnitude, duplicating millions or more copies of a particular DNA sequence, in order to detect the genetic material more easily.



Although effective, tests involving PCR may not be optimal for situations such as a pandemic outbreak, where results are needed quickly because PCR devices tend to be bulky and costly.



The Nanogap Sensor Array has a unique, vertically aligned nanostructure design and a two-surface configuration based on electronic transduction. The sensor comes with a pair of micro-sized metal electrodes separated by a nanogap (5 - 20 nm or about 1/50,000 the width of a human hair).



Another distinctive feature of the biosensor is its ability to capture DNA strands more effectively. This is possible because the two surfaces of the sensor are coated with a chemically treated "capture probe" solution through an electrochemical technique specially developed by IBN. This allows DNA strands to "stick" more easily to the sensor, resulting in a faster and more accurate analysis.



"This new biosensor holds significant promise to speed up on-going efforts in the detection and diagnosis of debilitating diseases such as cancer, cardiovascular problems and infectious viruses. We aim to make healthcare accessible to the masses with early disease diagnosis as the critical driving force behind the research we undertake here at IBN," added Jackie Y. Ying, Ph.D., Executive Director of IBN, one of the research institutes of Singapore's Agency for Science, Technology and Research (A*STAR).



The research was published on Aug. 5, 2009, in a paper titled, "Mass-Produced Nanogap Sensor Arrays for Ultrasensitive Detection of DNA," in Journal of the American Chemical Society.



Source:
Elena Tan


Nidyah Sani


Cathy Yarbrough


Agency for Science, Technology and Research (A*STAR), Singapore

Birds Could Teach Us A Thing Or Two About Healthy Eating

Want to know what kinds of foods prevent disease? Then watch what migratory birds eat during their stopovers on Block Island.



Two University of Rhode Island scientists believe that birds choose certain berries because they offer protection against oxidative stress that occurs during long flights. Oxidative stress can lead to inflammation and a variety of diseases in birds and humans.



The team's preliminary findings show that birds stopping over on Block Island favor the arrow-wood berry, which contains more anti-oxidants and pigments than the 11 other island berries studied by the researchers.



Navindra Seeram, assistant professor of pharmacy and head of the Bioactive Botanical Research Laboratory at URI, and Scott McWilliams, URI professor of wildlife ecology and physiology, have teamed up to research migratory birds' eating habits and how their diets might be used to understand the role of berries rich in anti-oxidants in human health. Research has shown a diet rich in anti-oxidants can help prevent cancer and other serious illnesses.



Seeram reported the findings at the American Chemical Society's 239th national meeting in San Francisco.



"We're suggesting that birds choose deeply colored berry fruits in part because of their anti-oxidant properties," Seeram said.



About 11 years before Seeram arrived at URI, McWilliams began laying the foundation for the recent study.



"When I started studying birds during their migratory stopover on Block Island, I was impressed that most of the migratory birds ate berry fruits even though they usually eat insects or seeds at other times of the year," said McWilliams, who came to URI in 1999. "I began studying the relationship between the nutritional qualities of fruits and how those nutrients might fuel migration."



When Seeram arrived at URI two years ago, McWilliams saw a University story online that detailed Seeram's research interests.



"I saw the story about Navindra and in it he was talking about oxidative stress and inflammation and the effects berry fruits can have on reducing those impacts on people."



So McWilliams, who does his research and teaches in the College of the Environment and Life Sciences, tracked down Seeram, who works in the College of Pharmacy. They developed their mutual research interests into a successful collaboration that included URI graduate student Jessica Bolser and post-doctoral researcher Liya Li, who works in Seeram's lab.



Called the lynchpin between McWilliams and Seeram, Bolser spent months in the field on Block Island observing the birds' nutritional patterns and collecting batches of 12 different kinds of berries for their analysis of anti-oxidant levels.



The research indicates that birds prefer to eat certain fruits that have more antioxidants and key nutrients. In return, the seeds in the berries are dispersed by the birds. "It's the way plants ensure their survival. Birds eat the berries, digest them and defecate the seeds over wide areas," McWilliams said.



"Meanwhile, the birds are attracted to the berries because of their rich color, which we believe is a plant's response to the stress of constant exposure to the sun and other stresses. Berry color could be a plant's way of fighting oxidative stress. It's a partnership that benefits plant and bird."



The Seeram-McWilliams partnership will continue. "We've only measured a few of these anti-oxidants," Seeram said. "Our next step is to determine how birds can detect these compounds."



"Whenever we exercise, we undergo oxidative stress, and the same is true for birds," McWilliams said. "We're flying birds in wind tunnels to produce oxidative stress, and then we are going to see if anti-oxidants found in these berries alleviate that stress," McWilliams said.



The research may benefit human health as well as bird conservation. If further research shows the direct link between bird health and diet, then the findings will play a critical role in habitat protection for migratory birds, McWilliams said.



"That's what is so great about URI," Seeram said. "Because the University is small, without the usual bureaucratic walls, we can create these partnerships. This collaboration between professors in two separate colleges would not have happened so easily in other universities and produced results so quickly."



Source:

Dave Lavallee


University of Rhode Island

Union Of Chemistry And Nanotechnology Should Improve Identification And Treatment Of Bacterial Infections

A new technique developed by a University of Central Florida chemist will help physicians more quickly identify the bacterial infections patients have so they can be treated in hours instead of days.



As more bacterial strains resistant to many drugs emerge, it becomes more critical to quickly identify infections and the antibiotics that would most effectively treat them. Such quick identifications become even more important during epidemics because large numbers of samples would have to be tested at once.



Assistant Professor J. Manuel Perez's new technique also promises to give research institutes and pharmaceutical companies a quicker and cheaper way of developing new antibiotics to combat super bugs.



The results of Perez's study were recently published online in Analytical Chemistry. The research was funded in part by the National Institutes of Health.



"The method really gives doctors quicker access to test results so they can treat their patients more quickly," Perez said from his lab at the Nanoscience Technology Center at UCF. "But there are more applications. This method can also be used by research facilities and big pharmaceutical companies for the high throughput screening of drugs for antibacterial activity."



Perez uses gold nanoparticles coated with a sugar and a protein that binds to sugars. Meanwhile, a variety of antibiotics are placed in the same solution. A spectrophotometer reads optical variations in the gold nanoparticle solution as the sugar and protein shift , which in turn demonstrate which antibiotics effectively halt bacteria growth and which ones do not. Results can be obtained within a couple of hours, in contrast to the traditional methods, which can take days to complete. And hundreds of samples can be tested at once using this technique because the amount of bacteria and antibiotic needed is small.



Pharmaceutical companies can use existing equipment to read the variations, which means they do not have to buy new equipment. Perez's study also shows that the technique is as sensitive and accurate as the traditional, more time-consuming approach.



"We're very excited and very pleased with the results," Perez said.







The research was completed with the help of the UCF Chemistry Department and the Burnett School of Biomedical Sciences. Nanoscience Technology Center post-doctoral fellow Sudip Nath and graduate student Charalambos Kaittanis are co-authors of the study, as is Alisa Tinkham, formerly of the Burnett School.



UCF Stands for Opportunity -- Established in 1963, the University of Central Florida is a diverse metropolitan research university that ranks as the 6th-largest in the country with more than 48,000 students. Located in Orlando, Fla., UCF offers high-quality undergraduate and graduate education, student development, and continuing education, while conducting cutting-edge research that powers the region's economic development.



Source: Zenaida Gonzalez Kotala


University of Central Florida