Scientists Crack the Spiders' Web Code

Decorative white silk crosses are an ingenious tactic used by orb-weaving spiders to protect their webs from damage, a new study from the University of Melbourne has revealed.

The team, led by Dr Andre Walter and Professor Mark Elgar from the University of Melbourne's Department of Zoology, found that orb-weaving spiders respond to severe damage to their webs by building bigger silk crosses, but if the damage is mild they don't bother adding extra decoration.

Professor Mark Elgar said web damage is costly for spiders as a lot of nutritional resources are required to rebuild a web. "So they evolved this ingenious way to minimise unwanted damage," he said.

"It's much like we mark glass windows with tape to prevent people walking into them," he said.

The team collected a group of orb-weaving spiders and left them to build their webs in the laboratory. Some of the completed webs were severely damaged, others lightly damaged and the remainder left alone. The response of the spiders was then observed.

"The fact that spiders increased their decorating activity in response to severe damage but didn't increase their decorating following light damage suggests that the conspicuous building of silk crosses serves to make webs more visible to animals that might accidentally walk or fly into them," Professor Elgar said.

Adding silk decorations to spiders' orb-webs was first reported over a century ago but why these spiders decorate their webs has been the topic of controversial debate for decades.

"Our study helps unravel this mystery," Professor Elgar said.

The study was published in Behavioural Ecology and Sociobiology.

Journal Reference:

1. André Walter, Mark A. Elgar. Signals for damage control: web decorations in Argiope keyserlingi (Araneae: Araneidae). Behavioral Ecology and Sociobiology, 2011; DOI: 10.1007/s00265-011-1200-8

Courtesy: ScienceDaily

Preventing the Spread of HIV/AIDS With Humanized BLT Mice

The more than 2.7 million new HIV infections recorded per year leave little doubt that the HIV/AIDS epidemic continues to spread globally. That's why there's the need for safe, inexpensive and effective drugs to successfully block HIV transmission.

A new study from the University of North Carolina at Chapel Hill School of Medicine further validates the use of humanized BLT mice in the fight to block HIV transmission. The "BLT" name is derived from the fact that these designer mice are created one at a time by introducing human bone marrow, liver and thymus tissues into animals without an immune system of their own. Humanized BLT mice have a fully functioning human immune system and can be infected with HIV in the same manner as humans.

The pioneering developers of the humanized BLT mouse model are Paul Denton, PhD, instructor of medicine and J. Victor Garcia-Martinez, PhD, professor of medicine in the UNC Center for Infectious Diseases and the UNC Center for AIDS Research.

In the study published online May 18 in the Journal of Virology, Denton and colleagues provide data that validates humanized BLT mice as a preclinical experimental system that potentially can be used to develop and test the effectiveness of experimental HIV prevention approaches and topical microbicides.

The animal study reproduced the design and methods of a recent double-blind clinical study in 889 women of the topical microbicide tenofovir. That study, the CAPRISA 004 trial, tested topical pre-exposure prophylaxis (PrEP) with 1 percent tenofovir which participants were instructed to apply vaginally twice daily. The 2.5 year trial resulted in an overall 39 percent reduction in instances of vaginal HIV transmission. Among women who self-reported as strongly adhered to the recommended instructions the protection figure climbed to 54 percent.

The new topical PrEP study by Denton and coauthors in humanized BLT mice reproduced the CAPRISA experimental design with tenofovir. The researchers say they "observed "88 percent protection of vaginal HIV-1 transmission," which was further confirmed by lack of detectable virus anywhere in the animals.

The researchers then tested six additional microbicide drug candidates for their ability to prevent vaginal HIV transmission. These experimental compounds, not yet tested in people, interfere with the virus' ability to reproduce. Partial or complete protection was shown by all but one of these drug candidates. Based on these positive results, Denton said these inhibitor drugs warrant serious consideration for future testing in people.

"This animal model has great potential value for testing and predicting the HIV preventive benefits of the second generation of microbicide candidates that are aimed at preventing viral replication," Garcia said. "The results of these studies will help provide important information for current and future clinical trials."

Also involved in the study were researchers from the University of Texas Southwestern Medical Center, University of Utah School of Medicine, The Scripps Research Institute, National Cancer Institute, and Weill Cornell Medical College.

Journal Reference:

1. paul W. Denton, Florence Othieno, Francisco Martinez-Torres, Wei Zou, John F. Krisko, Elisa Fleming, Sima Zein, Daniel A. Powell, Angela Wahl, Youn Tae Kwak, Brett D. Welch, Michael S. Kay, Deborah A. Payne, Philippe Gallay, Ettore Appella, Jacob D. Estes, Min Lu, J. Victor Garcia. Topically Applied 1% Tenofovir in Humanized BLT Mice Using the CAPRISA 004 Experimental Design Demonstrates Partial Protection from Vaginal HIV Infection Validating the BLT Model for the Evaluation of New Microbicide Candidates. Journal of Virology, 2011; DOI: 10.1128/JVI.00537-11

Courtesy: ScienceDaily

Key to Fighting Drug-Resistant Leukemia Discovered

Doctors who treat children with the most common form of childhood cancer -- acute lymphoblastic leukemia -- are often baffled at how sometimes the cancer cells survive their best efforts and the most powerful modern cancer drugs.

Now a team of scientists led by researchers at the University of California, San Francisco has uncovered the basis for this drug resistance: BCL6, a protein that leukemia cells use to stay alive. Targeting this protein may be the key to fighting drug-resistant leukemia, a discovery that may make cancer drugs more powerful and help doctors formulate powerful drug cocktails to cure more children of leukemia.

"We believe this discovery is of immediate relevance to patient care," said Markus Müschen, MD, PhD, a professor of laboratory medicine at UCSF and the senior author on the study.

As described in the journal Nature this week, Müschen and his colleagues showed that mice with drug-resistant leukemia can be cured of the disease when given conventional cancer drugs in combination with a compound that disables the BCL6 protein. This compound was initially developed by Ari Melnick, a professor of pharmacology at the Weill Cornell College of Medicine in New York and a co-author of the study.

A Common Form Of Cancer In Children

Acute lymphoblastic leukemia is the most common form of cancer in children and accounts for about 23 percent of all cases of cancer in children under the age of 15, according to the National Cancer Institute.

In this form of cancer, leukemia cells in the bloodstream and bone marrow continuously multiply, crowding out other, healthy cells. The disease progresses rapidly, and the leukemia cells begin to infiltrate tissues in other parts of the body. Treatment is neither cheap nor easy -- but it can be miraculous. It usually involves a long course of drugs that can be physically and emotionally taxing for the children and their parents. Once finished, many enjoy complete remission and are able to live cancer-free, cured of the leukemia.

Still a large number of children are not cured and ultimately succumb to the disease. In those cases, some of the cancer cells resist the therapy and survive quietly in the body. When the cancer reemerges, it is no longer sensitive to the drugs.

In their new report, Müschen and his colleagues show that the key to this resistance is the protein BCL6, offering the first evidence of how the cancer cells managed to survive.

"It is something like an emergency mechanism whereby tumor cells try to evade drug-treatment," Müschen said.

One Among 22,000 Genes

The work started four years ago when Müschen wanted to figure out what happens to cancer cells during cancer treatments. He and his colleagues exposed leukemia cells in the petri dish to drugs and then looked at how they responded to the treatment. They analyzed how the expression of 22,000 different genes changed when different cancer cells were given different drugs, and they found that BCL6 levels always rocketed up following treatment.

The BCL6 protein was already known to cancer researchers because it is active in other forms of cancer. In lymphoma, for instance, BCL6 protects cancer cells from dying, and the protein has long been the target for research and drug design. But it had never been connected to leukemia.

Reasoning that blocking BCL6 would make leukemia cells more sensitive to chemotherapy, the scientists showed exactly that. Working with Melnick and colleagues at Weill-Cornell Medical College in New York City who had developed a biotech drug-like peptide that blocks BCL6, they showed that giving the peptide to mice along with anti-leukemia drugs increased the potency of conventional drugs and helped the mice survive the disease.

Now Müschen is looking for ways to do the same thing with small molecules, which are generally easier to formulate into an oral drug and cheaper to mass produce than biotech drugs like peptides.

Last year, he was awarded a $3.6 million grant from the California Institute for Regenerative Medicine (CIRM) to develop such a molecule.

The article was authored by Cihangir Duy, Christian Hurtz, Seyedmehdi Shojaee, Leandro Cerchietti, Huimin Geng, Srividya Swaminathan, Lars Klemm, Soo-mi Kweon, Rahul Nahar, Melanie Braig, Eugene Park, Yong-mi Kim, Wolf-Karsten Hofmann, Sebastian Herzog, Hassan Jumaa, H. Phillip Koeffler, J. Jessica Yu, Nora Heisterkamp, Thomas G. Graeber, Hong Wu, B. Hilda Ye, Ari Melnick and Markus Müschen.

In addition to scientists at UCSF and Weill Cornell Medical College in New York City, the team included researcher at the Children's Hospital Los Angeles and University of Southern California, Universitatsklinikum Hamburg-Eppendorf in Hamburg, Germany, Cedars Sinai Medical Center in Los Angeles, the Albert-Ludwigs-Universitat Freiburg and Max-Planck-Institute for Immunobiology in Freiburg, Germany, Universitat Heidelberg, Klinikum Mannheim, Mannheim, Germany, Albert Einstein College of Medicine in New York City, and the University of California, Los Angeles.

This work was supported by grants from the National Institutes of Health and the National Cancer Institute, grants from the Leukemia and Lymphoma Society, the California Institute for Regenerative Medicine, the William Laurence and BlancheHughes Foundation and a StandUp To Cancer-American Association for Cancer Research Innovative Research Grant. Markus Müschen and Ari Melnick are Scholars of the Leukemia and Lymphoma Society.

Journal Reference:

1. Cihangir Duy, Christian Hurtz, Seyedmehdi Shojaee, Leandro Cerchietti, Huimin Geng, Srividya Swaminathan, Lars Klemm, Soo-mi Kweon, Rahul Nahar, Melanie Braig, Eugene Park, Yong-mi Kim, Wolf-Karsten Hofmann, Sebastian Herzog, Hassan Jumaa, H. Phillip Koeffler, J. Jessica Yu, Nora Heisterkamp, Thomas G. Graeber, Hong Wu, B. Hilda Ye, Ari Melnick, Markus Müschen. BCL6 enables Ph acute lymphoblastic leukaemia cells to survive BCR–ABL1 kinase inhibition. Nature, 2011; 473 (7347): 384 DOI: 10.1038/nature09883

Courtesy: ScienceDaily

When Rising PSA Means Prostate Cancer Is in Patient's Future

A man's rising PSA (prostate-specific antigen) level over several years -- which had been seen as a possible warning sign of prostate cancer -- has recently come under fire as a screening test because it sometimes prompts biopsies that turn out to be normal.

A new study, however, shows nearly 70 percent of men who had rising PSA levels and subsequent normal biopsies were eventually diagnosed with prostate cancer, according to research from Northwestern University Feinberg School of Medicine. The trend of a PSA level over several years is called PSA velocity.

"Our findings show an elevated and rising PSA level or velocity should lead a clinician to follow a patient more closely, even if he has a negative biopsy," said lead investigator William Catalona, M.D., director of the clinical prostate cancer program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "One negative biopsy isn't the end of the road."

The findings were presented May 18 at the American Urological Association 2011 Annual Meeting. Catalona is a professor of urology at the Feinberg School and a urologist at Northwestern Memorial Hospital.

PSA is a substance whose elevated levels can indicate prostate cancer but can also be caused by prostate inflammation or enlargement or other conditions. Catalona, known as the father of the PSA screening, was the first to show in 1991 that a simple blood test measuring PSA levels could be used to detect prostate cancer.

For the study, Northwestern researchers looked in their database at the history of 97 patients with a rising PSA trend (or velocity) who had a subsequent negative biopsy. Researchers found 66 percent of patients were eventually diagnosed with prostate cancer, 20 percent had a benign prostate, 8 percent had protatitis and 6 percent had premalignant lesions.

"This underscores the importance of using a patient's individual PSA trend when deciding whether to pursue a prostate biopsy," said co-investigator Gregory Auffenberg, M.D., a resident in urology at the Feinberg School. "It's not enough to only look at an individual PSA value when historical data is also available."

The research was supported in part by the Urological Research Foundation, Prostate SPORE Grant and a Lurie Cancer Center grant.

Story Source:

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

Courtesy: ScienceDaily

Lack of 'Gatekeeper' Protein Linked to Skin Cancer

New research from North Carolina State University shows that a "gatekeeper" protein plays an important role in skin-cancer prevention in humans and lab mice.

The protein, C/EBP alpha, is normally abundantly expressed to help protect skin cells from DNA damage when humans are exposed to sunlight. The NC State research shows, however, that the protein is not expressed when certain human skin cancers are present.

Moreover, when the protein is inactivated in special lab mice exposed to small amounts of the UVB solar radiation, the mice become more susceptible to skin cancer.

Dr. Robert Smart, professor of environmental and molecular toxicology at NC State and the corresponding author of a paper in the Journal of Investigative Dermatology describing the research, says that C/EBP alpha serves as an important "pause button" in cells. If there is any DNA damage, C/EBP alpha halts the cell-replication process to allow time for cells to repair themselves to prevent DNA errors from occurring.

"Loss of C/EBP alpha expression is associated with some of the most common human cancers, including breast and colon cancer," Smart says. "We think it may also have a role in tumor suppression in these cancers via its gatekeeper function."

In the study, the researchers found that human skin expresses C/EBP alpha as does the pre-cancerous, benign lesion called actinic keratose -- the precursor to skin cancer.

"C/EBP alpha is expressed in normal human skin and in pre-cancerous actinic keratoses, but something happens when cancerous lesions appear -- the protein is not expressed," Smart says. "We then asked, 'Is the loss of C/EBP alpha contributing to tumor formation?' The answer seems to be yes."

Smart and colleagues exposed hairless, genetically modified mice -- bred with C/EBP alpha inactivated -- to low doses of the UVB solar radiation. The mice were highly susceptible to certain common types of skin cancer -- squamous cell carcinomas -- with these cancerous tumors developing and growing rapidly.

"If you can figure out how to keep C/EBP alpha turned on, maybe the tumor would stay in its pre-cancerous state," Smart says.

Smart adds that figuring out how the protein fulfills its gatekeeper role -- and how and why the protein is inactivated in cancerous cells -- marks the next step in his research.

The research was funded by the National Institute of Environmental Health Sciences and the National Cancer Institute. Colleagues from the University of Chicago and Columbia University contributed to the study, as did graduate students and postdocs in Smart's laboratory.

Journal Reference:

1. Elizabeth A. Thompson, Songyun Zhu, Jonathan R. Hall, John S. Hoose, Rakesh Ranjan, Jeanne A. Burr, Robert C. Smart, Yu-Ying He and David M. Owens. C/EBP alpha Expression is Downregulated in Human Nonmelanoma Skin Cancers and Inactivation of C/EBP alpha Confers Susceptibility to UVB-Induced Skin Squamous Cell Carcinomas. Journal of Investigative Dermatology, June 2011

Courtesy: ScienceDaily

Origami Not Just for Paper Anymore: DNA, Folded Into Complex Shapes, Could Have a Big Impact on Nanotechnology

While the primary job of DNA in cells is to carry genetic information from one generation to the next, some scientists also see the highly stable and programmable molecule as an ideal building material for nanoscale structures that could be used to deliver drugs, act as biosensors, perform artificial photosynthesis and more.

Trying to build DNA structures on a large scale was once considered unthinkable. But about five years ago, Caltech computational bioengineer Paul Rothemund laid out a new design strategy called DNA origami: the construction of two-dimensional shapes from a DNA strand folded over on itself and secured by short "staple" strands. Several years later, William Shih's lab at Harvard Medical School translated this concept to three dimensions, allowing design of complex curved and bent structures that opened new avenues for synthetic biological design at the nanoscale.

A major hurdle to these increasingly complex designs has been automation of the design process. Now a team at MIT, led by biological engineer Mark Bathe, has developed software that makes it easier to predict the three-dimensional shape that will result from a given DNA template. While the software doesn't fully automate the design process, it makes it considerably easier for designers to create complex 3-D structures, controlling their flexibility and potentially their folding stability.

"We ultimately seek a design tool where you can start with a picture of the complex three-dimensional shape of interest, and the algorithm searches for optimal sequence combinations," says Bathe, the Samuel A. Goldblith Assistant Professor of Applied Biology. "In order to make this technology for nanoassembly available to the broader community -- including biologists, chemists, and materials scientists without expertise in the DNA origami technique -- the computational tool needs to be fully automated, with a minimum of human input or intervention."

Bathe and his colleagues described their new software in the Feb. 25 issue of Nature Methods. In that paper, they also provide a primer on creating DNA origami with collaborator Hendrik Dietz at the Technische Universitaet Muenchen. "One bottleneck for making the technology more broadly useful is that only a small group of specialized researchers are trained in scaffolded DNA origami design," Bathe says.

Programming DNA

DNA consists of a string of four nucleotide bases known as A, T, G and C, which make the molecule easy to program. According to nature's rules, A binds only with T, and G only with C. "With DNA, at the small scale, you can program these sequences to self-assemble and fold into a very specific final structure, with separate strands brought together to make larger-scale objects," Bathe says.

Rothemund's origami design strategy is based on the idea of getting a long strand of DNA to fold in two dimensions, as if laid on a flat surface. In his first paper outlining the method, he used a viral genome consisting of approximately 8,000 nucleotides to create 2-D stars, triangles and smiley faces.

That single strand of DNA serves as a "scaffold" for the rest of the structure. Hundreds of shorter strands, each about 20 to 40 bases in length, combine with the scaffold to hold it in its final, folded shape.

"DNA is in many ways better suited to self-assembly than proteins, whose physical properties are both difficult to control and sensitive to their environment," Bathe says.

Bathe's new software program interfaces with a software program from Shih's lab called caDNAno, which allows users to manually create scaffolded DNA origami from a two-dimensional layout. The new program, dubbed CanDo, takes caDNAno's 2-D blueprint and predicts the ultimate 3-D shape of the design. This resulting shape is often unintuitive, Bathe says, because DNA is a flexible object that twists, bends and stretches as it folds to form a complex 3-D shape.

According to Rothemund, the CanDo program should allow DNA origami designers to more thoroughly test their DNA structures and tweak them to fold correctly. "While we have been able to design the shape of things, we have had no tools to easily design and analyze the stresses and strains in those shapes or to design them for specific purposes," he says.

At the molecular-level, stress in the double helix of DNA decreases the folding stability of the structure and introduces local defects, both of which have hampered progress in the scaffolded DNA origami field.

Postdoctoral researcher Do-Nyun Kim and graduate student Matthew Adendorff, both of the Bathe lab, are now furthering CanDo's capabilities and optimizing the scaffolded DNA origami design process.

Building nanoscale tools

Once scientists have a reliable way to assemble DNA structures, the next question is what to do with them. One application scientists are excited about is a "DNA carrier" that can transport drugs to specific destinations in the body such as tumors, where the carrier would release the cargo based on a specific chemical signal from the target cancer cell.

Another possible application of scaffolded DNA origami could help reproduce part of the light-harvesting apparatus of photosynthetic plant cells. Researchers hope to recreate that complex series of about 20 protein subunits, but to do that, components must be held together in specific positions and orientations. That's where DNA origami could come in.

"DNA origami enables the nanoscale construction of very precise architectural arrangements. Researchers are exploiting this unique property to pursue a number of applications at the nanoscale, including a synthetic photocell," Bathe says. "While applications such as this are still quite far off on the horizon, we believe that predictive engineering software tools are essential for progress in this direction."

Novel applications may also grow out of a new competition being held at Harvard this summer, called BIOMOD. Undergraduate teams from about a dozen schools, including MIT, Harvard and Caltech, will try to design nanoscale biomolecules for robotics, computing and other applications.

In the meantime, Bathe is focusing on further developing CanDo to enable automated DNA origami design. "Once you have an automated computational tool that allows you to design complex shapes in a precise way, I think we're in a much better position to exploit this technology for interesting applications," he says.

For DNA origami to have a broad impact, it needs to become routine to simply order up DNA parts to build any configuration you can dream up, Bathe says. He notes: "Once non-specialists can design arbitrary 3-D nanostructures using DNA origami, their imaginations can run free."

Journal Reference:

1. Carlos Ernesto Castro, Fabian Kilchherr, Do-Nyun Kim, Enrique Lin Shiao, Tobias Wauer, Philipp Wortmann, Mark Bathe, Hendrik Dietz. A primer to scaffolded DNA origami. Nature Methods, 2011; 8 (3): 221 DOI: 10.1038/nmeth.1570

Courtesy: ScienceDaily

Cardiac Arrest: Unique Life-Saving Device Give Heart a Second Chance

An invention by Rice University bioengineering students in collaboration with the Texas Heart Institute (THI) is geared toward giving immediate second chances to arrhythmia victims headed toward cardiac arrest.

For their capstone design project, a team of Rice seniors created a unique pad system for automated external defibrillators (AEDs), common devices that can shock a victim's heart back into a proper rhythm in an emergency.

Often, the first shock doesn't reset a heart and the procedure must be repeated, but the sticky pads on the chest must first be repositioned. The pads need to be in the right location to send current through the heart, and someone with no experience who tries to provide aid might miss the first time.

The Second-Chance AED Pads let rescuers try again without losing valuable time to remove the pads from the victim's chest. The pads incorporate three electrodes, two in a single pad with an A/B switch attached, and a third in its own pad.

If one shock doesn't restart the patient's heart, flipping the switch will change the jolt's path, just a little bit, for the second attempt.

The pads were developed by students on the DefibTaskForce -- Lisa Jiang, Joanna Nathan, Justin Lin, Carl Nelson and Brad Otto -- in tandem with Mehdi Razavi, director of electrophysiology clinical research at THI, and their adviser, Renata Ramos, a Rice lecturer in bioengineering.

The potential for their project was clear from the beginning. "We did some calculations that suggested we could save at least 13,000 lives per year," Otto said. "Cardiac defibrillation is very time-sensitive. Thirty seconds can be the difference between life and death in a lot of situations. The time it takes to flip the switch is negligible compared with the time it takes to remove the pads, shave and prep a new area on the body, reapply the pads and administer another shock. And a layman might not even know to try a second position."

Rather than try to build a new type of AED, the team decided early on that it was enough to simply design new pads that would fit devices that are already in use. Manufacturers generally require AED pads be replaced every two years, which provides a ready market for the students' invention. "But well over 100,000 AED units are produced every year, so even if our pads are only paired with new AEDs, we have a significant market," Lin said.

Getting the instructions right turned out to be just as important as the device itself and required a lot of illustrative trial and error. In tests for the final version at Rice's Oshman Engineering Design Kitchen, the team recruited students with no experience using an AED to shock a medical mannequin back to life. "We had 100 percent of the testers place the pads correctly, showing it was very intuitive to use," Jiang said.

All five team members, along with Razavi and Ramos, are listed on the provisional patent. They hope an AED manufacturer will pick up the rights to the Second-Chance pads for clinical trials and ultimately FDA approval.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Rice University.

Courtesy: ScienceDaily

Researchers Discover Mechanism That Could Convert Certain Cells Into Insulin-Making Cells

Simply put, people develop diabetes because they don't have enough pancreatic beta cells to produce the insulin necessary to regulate their blood sugar levels. But what if other cells in the body could be coaxed into becoming pancreatic beta cells? Could we potentially cure diabetes?

Researchers from UCLA's Larry L. Hillblom Islet Research Center have taken an important step in that direction. They report in the April issue of the journal Developmental Cell that they may have discovered the underlying mechanism that could convert other cell types into pancreatic beta cells.

While the current standard of treatment for diabetes -- insulin therapy -- helps patients maintain sugar levels, it isn't perfect, and many patients remain at high risk of developing a variety of medical complications. Replenishing lost beta cells could serve as a more permanent solution, both for those who have lost such cells due to an immune assault (Type 1 diabetes) and those who acquire diabetes later in life due to insulin resistance (Type 2).

"Our work shows that beta cells and related endocrine cells can easily be converted into each other," said study co-author Dr. Anil Bhushan, an associate professor of medicine in the endocrinology division at the David Geffen School of Medicine at UCLA and in the UCLA Department of Molecular, Cell and Developmental Biology.

It had long been assumed that the identity of cells was "locked" into place and that they could not be switched into other cell types. But recent studies have shown that some types of cells can be coaxed into changing into others -- findings that have intensified interest in understanding the mechanisms that maintain beta cell identity.

The UCLA researchers show that chemical tags called "methyl groups" that bind to DNA -- where they act like a volume knob, turning up or down the activity of certain genes -- are crucial to understanding how cells can be converted into insulin-secreting beta cells. They show that DNA methylation keeps ARX, a gene that triggers the formation of glucagon-secreting alpha cells in the embryonic pancreas, silent in beta cells.

Deletion of Dnmt1, the enzyme responsible for DNA methylation, from insulin-producing beta cells converts them into alpha cells.

These findings suggest that a defect in beta cells' DNA methylation process interferes with their ability to maintain their "identity." So if this "epigenetic mechanism," as the researchers call it, can produce alpha cells, there may be an analogous mechanism that can produce beta cells that would maintain blood sugar equilibrium.

"We show that the basis for this conversion depends not on genetic sequences but on modifications to the DNA that dictates how the DNA is wrapped within the cell," Bhushan said. "We think this is crucial to understanding how to convert a variety of cell types, including stem cells, into functional beta cells."

According to the American Diabetes Association, 25.8 million children and adults in the U.S. -- 8.3 percent of the population -- have diabetes.

The National Institute of Diabetes and Digestive and Kidney Diseases, the Juvenile Diabetes Research Foundation, and the Helmsley Trust funded this study.

Additional co-authors of the study are Sangeeta Dhawan, Senta Georgia, Shuen-ing Tschen and Guoping Fan, all of UCLA.

Journal Reference:

1. Sangeeta Dhawan, Senta Georgia, Shuen-ing Tschen, Guoping Fan, Anil Bhushan. Pancreatic β Cell Identity Is Maintained by DNA Methylation-Mediated Repression of Arx. Developmental Cell, 2011; 20 (4): 419 DOI: 10.1016/j.devcel.2011.03.012

Courtesy: ScienceDaily