A new technique using near-infrared images, obtained with ESO’s 3.58-metre New Technology Telescope (NTT), allows astronomers to see through the opaque dust lanes of the giant cannibal galaxy Centaurus A, unveiling its “last meal” in unprecedented detail — a smaller spiral galaxy, currently twisted and warped. This amazing image also shows thousands of star clusters, strewn like glittering gems, churning inside Centaurus A.

Comparison between a visible-light image (left) of Centaurus A, as seen with the Wide-Field Imager on the MPG/ESO 2.2-metre telescope, and a near-infared view (right) obtained with the SOFI instrument on ESO’s New Technology Telescope, also at La Silla. (ESO)

Centaurus A (NGC 5128) is the nearest giant, elliptical galaxy, at a distance of about 11 million light-years. One of the most studied objects in the southern sky, by 1847 the unique appearance of this galaxy had already caught the attention of the famous British astronomer John Herschel, who catalogued the southern skies and made a comprehensive list of nebulae.

Herschel could not know, however, that this beautiful and spectacular appearance is due to an opaque dust lane that covers the central part of the galaxy. This dust is thought to be the remains of a cosmic merger between a giant elliptical galaxy and a smaller spiral galaxy full of dust.

Between 200 and 700 million years ago, this galaxy is indeed believed to have consumed a smaller spiral, gas-rich galaxy — the contents of which appear to be churning inside Centaurus A’s core, likely triggering new generations of stars.

First glimpses of the “leftovers” of this meal were obtained thanks to observations with the ESA Infrared Space Observatory , which revealed a 16 500 light-year-wide structure, very similar to that of a small barred galaxy. More recently, NASA’s Spitzer Space Telescope resolved this structure into a parallelogram, which can be explained as the remnant of a gas-rich spiral galaxy falling into an elliptical galaxy and becoming twisted and warped in the process. Galaxy merging is the most common mechanism to explain the formation of such giant elliptical galaxies.

The new SOFI images, obtained with the 3.58-metre New Technology Telescope at ESO’s La Silla Observatory, allow astronomers to get an even sharper view of the structure of this galaxy, completely free of obscuring dust. The original images, obtained by observing in the near-infrared through three different filters (J, H, K) were combined using a new technique that removes the dark, screening effect of the dust, providing a clear view of the centre of this galaxy.

What the astronomers found was surprising: “There is a clear ring of stars and clusters hidden behind the dust lanes, and our images provide an unprecedentedly detailed view toward it,” says Jouni Kainulainen, lead author of the paper reporting these results. “Further analysis of this structure will provide important clues on how the merging process occurred and what has been the role of star formation during it.”

The research team is excited about the possibilities this new technique opens: “These are the first steps in the development of a new technique that has the potential to trace giant clouds of gas in other galaxies at high resolution and in a cost-effective way,” explains co-author João Alves. “Knowing how these giant clouds form and evolve is to understand how stars form in galaxies.”

This image of the central parts of Centaurus A reveals the parallelogram-shaped remains of a smaller galaxy that was gulped down about 200 to 700 million years ago. The image is based on data collected with the SOFI instrument on ESO’s New Technology Telescope at La Silla.(ESO)

Looking forward to the new, planned telescopes, both on the ground and in space, “this technique is very complementary to the radio data ALMA will collect on nearby galaxies, and at the same time it poses interesting avenues of research for extragalactic stellar populations with the future European Extremely Large Telescope and the James Webb Space Telescope, as dust is omnipresent in galaxies,” says co-author Yuri Beletsky.

Previous observations done with ISAAC on the VLT (ESO 04/01) have revealed that a supermassive black hole lurks inside Centaurus A. Its mass is about 200 million times the mass of our Sun, or 50 times more massive than the one that lies at the centre of our Milky Way. In contrast to our own galaxy, the supermassive black hole in Centaurus A is continuously fed by material falling onto into it, making the giant galaxy a very active one. Centaurus A is in fact one of the brightest radio sources in the sky (hence the “A” in its name). Jets of high energy particles from the centre are also observed in radio and X-ray images.

The new image of Centaurus A is a wonderful example of how frontier science can be combined with aesthetic aspects. Fine images of Centaurus A have been obtained in the past with ESO’s Very Large Telescope (ESO PR Photo 05b/00) and with the Wide Field Imager on the MPG/ESO 2.2-metre telescope at La Silla.

This research was presented in a paper in Astronomy and Astrophysics (vol. 502): “Uncovering the kiloparsec-scale stellar ring of NGC5128”, by J.T. Kainulainen et al.

The team is composed of J. T. Kainulainen (University of Helsinki, Finland, and MPIA, Germany), J. F. Alves (Calar Alto Observatory, Spain and University of Vienna, Austria), Y. Beletsky (ESO), J. Ascenso (Harvard-Smithsonian Center for Astrophysics, USA), J. M. Kainulainen (TKK/Department of Radio Science and Engineering, Finland), A. Amorim, J. Lima, F. D. Santos, and A. Moitinho (SIM-IDL, University of Lisbon, Portugal), R. Marques and J. Pinhão (University of Coimbra, Portugal), and J. Rebordão (INETI, Amadora, Portugal).

SOFI (Son of ISAAC) is an infrared spectro-imager attached to ESO’s 3.58-metre New Technology Telescope (NTT) and a simplified version of the Short Wavelength arm of ISAAC on the Very Large Telescope.

- ESO, The European Southern Observatory -

IU Kelley School research pinpoints tactics that drive sales without eroding brand equity.

BLOOMINGTON, Ind. – Retailers beware. Some tried-and-true discounting tactics for pepping up holiday season sales can be a boon for some products — but a bust for others.

Photo by Paul Keleher

First-of-its kind research from the Indiana University Kelley School of Business confirms that certain kinds of point-of-purchase discounts can effectively attract more buyers in the short-term but for some products can tarnish sales and brand equity over time.

Researchers invited study participants — more than 100 university students — into an imaginary local grocery store where they were asked to shop “as they do in real life.” The researchers manipulated discount prices of common items and interviewed participants to determine how this might have influenced purchases. They found that for some products, placing discount messages in close proximity to discounted items was the most effective way to build sales.

Applying this knowledge to the marketplace, the researchers indicated that, for example, holiday shoppers looking for gift ideas in electronics stores would be more inclined to buy items like digital cameras flanked by “$50 Off, Limited Time Only” than they would be if they received the same message via regular mail.

Quick computing translates into sales

The study, titled “The Effects of Discount Location and Frame on Consumers’ Price Estimates,” also demonstrated that buyers are more inclined to make purchases when stores communicate discounts in ways that are instantly computable.

“Retailers should understand that most customers aren’t willing to calculate savings if they have to think too hard about the math and thus might not buy the product,” said H. Shanker Krishnan, professor of marketing at the Kelley School and co-author of the study. “Highlighting price reductions in simple, real dollar terms is a more compelling sales inducement than, say ‘25 percent off.”

However, the study noted that closely associating products with discounts can have negative implications over time.

“People come to associate certain prices with certain products,” said Krishnan. “If the discount message disappears, buyers may be put off and seek out discount prices on other, related products.”

Frequently purchased items, like music and clothing, are particularly susceptible to buyer resistance when discounts are removed. “The discounted prices are much more likely to become fixed and expected in shoppers’ minds,” said Krishnan.

On the other hand, the study showed that less frequently purchased items, like TVs, may be more immune to consumer price expectations. “The lifespan of durable items is such that shoppers forget what they last paid for them,” he said.

Luxury brands are special case

Then there is the issue of protecting brand equity. The study pointed out that point-of-purchase discounting requires a strategic, highly selective approach to ensure that certain products maintain their long-term sales potential.

H. Shanker Krishnan (Indiana University)

“It is particularly important that shoppers don’t come to associate luxury items with lower prices,” Krishnan said. “Otherwise, they’ll experience severe sticker-shock their next go-around — and brand loyalty can suffer.”

For luxury brands, the best bet might be to offer discounts via percentages and to physically separate the discount message from the product by using coupons, ads, general in-store promotions and other tactics. The price reductions may have a less telling, short-term impact on sales, but the brand equity will be protected.

Overall, said Krishnan, discounting can work very favorably for retailers if they make the effort to understand the complexities and make knowledgeable decisions.

“This seems like common sense,” he said, “but so often you see retailers seeking to maximize short-term sales while shooting themselves in the foot down the road.”

The study appeared in the September issue of Journal of Retailing. It was coauthored by Devon DelVecchio at Miami University in Ohio and Arun Lakshmanan at University of Buffalo, SUNY.

Indiana University

Researchers at Washington University School of Medicine in St. Louis have shed new light on a process that fixes breaks in the genetic material of the body’s cells. Their findings could lead to ways of enhancing chemotherapy drugs that destroy cancer cells by damaging their DNA.

An illustration of two proteins involved in DNA repair by artist Amy VanDonsel

Using yeast cells, the scientists studied protein molecules that have an important role in homologous recombination, which is one way that cells repair breaks in the DNA double helix. The process in yeast is similar to that in humans and other organisms.

Earlier research had established that a protein molecule named Srs2 regulates homologous recombination by counteracting the work of another protein, Rad51. Reporting in the July 10 issue of the journal Molecular Cell, the research team reveals the mechanism of how Srs2 removes Rad51 from DNA and thereby prevents it from making repairs to broken strands.

“Our findings may make it possible to uncover ways to augment the effect of DNA-damaging agents that are used for cancer chemotherapy,” says senior author Tom Ellenberger, D.V.M, Ph.D., the Raymond H. Wittcoff Professor and head of the Department of Biochemistry and Molecular Biophysics. “Many chemotherapeutic agents work by causing DNA damage in cancer cells, leading to their death, and tumors can become resistant to chemotherapy by using DNA repair mechanisms to keep the cells alive. Drugs that inhibit the DNA repair process could help increase the efficiency of chemotherapeutic agents.”

Ellenberger is also co-director of the Pharmacology Core at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University. The facility aids in the development of anti-cancer agents.

Srs2 is a helicase molecule — a motor protein that’s able to walk or slide along a strand of DNA and remove other proteins from DNA or separate the two strands of the twisted double helix. For studies of Srs2, Ellenberger’s laboratory collaborated with Timothy Lohman, Ph.D., the Marvin A. Brennecke Professor of Biochemistry and Molecular Biophysics, a prominent expert in the biochemistry of motor proteins like Srs2.

Rad51’s job in the cell is to promote the exchange of sequences between two related DNA molecules, which can be used to repair breaks in DNA where both strands of the double helix are compromised. As a DNA matchmaker, Rad51 forms long filaments on DNA. Srs2 can remove these to prevent unwanted exchanges of DNA sequences. Without Srs2, cells lose their ability to maintain the normal structure of chromosomes, and DNA sequences become shuffled.

The biochemists found that Srs2 possesses a small arm that interacts with Rad51 and triggers a chemical reaction within the Rad51 protein causing it to fall off the DNA.

“Scientists had assumed that as Srs2 moved along the DNA strand, it just pushed off everything in its path,” says lead author Edwin Antony, Ph.D., a postdoctoral research associate in biochemistry and molecular biophysics. “This isn’t the case — we showed that Srs2 has a specialized structure that allows it to interact specifically with Rad51.”

This finding shows how a motor protein like Srs2 can perform the specialized task of remodeling a protein-DNA complex without interference by other similar helicases, he adds.

Because they now know more precisely the nature of this interaction between Srs2 and Rad51, the researchers can narrow their search for drugs that will block DNA repair by Rad51. This type of drug could make a lower dose of a DNA-damaging drug effective in treating cancer.

The research team is now trying to identify the Srs2 homologue in human cells and will study its structure in combination with Rad51. That will allow a more rational approach to understanding how cells cope with DNA damage and how some tumors evade cancer therapeutics, they say.

“In the long-term, my laboratory will look for drug-like molecules that influence this interaction,” Ellenberger says. “We are using the Chemical Genetics Screening Center here at the University (http://htc.wustl.edu). It has vast libraries of molecules that may have the activity we want. Edwin’s work on Srs2 and Rad51 will allow us to develop an assay to screen for agents that augment or supersede Srs2’s interference with DNA repair.”

Antony E, Tomko EJ, Xiao Q, Krejci L, Lohman TM, Ellenberger T. Srs2 disassembles Rad51 filaments by a protein-protein interaction triggering ATP turnover and dissociation of Rad51 from DNA. Molecular Cell. 2009;35(1):105-115.

Funding from the National Institutes of Health and the Young Scientist Program at Washington University supported this research.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Siteman Cancer Center is the only federally designated Comprehensive Cancer Center within a 240-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine. Siteman has satellite locations in West County and St. Peters, in addition to its full-service facility at Washington University Medical Center on South Kingshighway.

By Gwen Ericson – Washington University in St. Louis, School of Medicine

WEST LAFAYETTE, Ind. – A new prostate cancer “homing device” could improve detection and allow for the first targeted treatment of the disease.

A new prostate cancer “homing device” could improve detection and allow for the first targeted treatment of the disease.

This image depicts transporter molecules carrying therapeutic drugs to PSMA targets on a prostate cancer cell. A Purdue research team designed a molecule that finds and penetrates prostate cancer cells and can transport drugs or imaging agents into the cell. (Image courtesy of Low laboratory)

A team of Purdue University researchers has synthesized a molecule that finds and penetrates prostate cancer cells and has created imaging agents and therapeutic drugs that can link to the molecule and be carried with it as cargo.

A radioimaging application used for body scans is expected to enter clinical trials this fall, and an optical imaging application used to measure prostate cancer cells in blood samples is already in clinical trials.

Philip Low, the Ralph C. Corley Distinguished Professor of Biochemistry who led the team, said a targeted treatment could be much more effective in treating cancer and would greatly reduce the harmful side effects associated with current treatments.

“Currently none of the drugs available to treat prostate cancer are targeted, which means they go everywhere in the body as opposed to only the tumor, and so are quite toxic for the patient,” said Low, who is a member of the Purdue Cancer Center. “By being able to target only the cancer cells, we could eliminate toxic side effects of treatments. In addition, the ability to target only the cancer cells can greatly improve imaging of the cancer to diagnose the disease, determine if it has spread or is responding to treatment.”

Prostate cancer is the most common cancer, other than skin cancers, and is the second leading cause of cancer death in American men, according to the American Cancer Society. It is estimated that about 192,280 new cases will be diagnosed and 27,360 men will die of prostate cancer in the United States this year.

The molecule Low’s team created attaches to prostate-specific membrane antigen, or PSMA, a protein that is found on the membrane of more than 90 percent of all prostate cancers. It also is found on the blood vessels of most solid tumors and could provide a way to cut off the tumor blood supply, Low said.

“A lot of new drugs are being designed to destroy the vasculature of solid tumors, and, if they could be linked to this new targeting molecule, we could have a two-pronged attack for prostate cancer,” he said. “We could not only kill the prostate cancer cells directly, we could also destroy the vasculature that feeds the tumors.”

There also is potential for the targeting molecule to be used to attack the vasculature of solid tumors of other types of cancers, Low said.

Two papers detailing the work of the Purdue team were published in the June 1 issue of Molecular Pharmaceutics. Endocyte Inc. funded the work.

The team’s animal study data shows an ability to eliminate human prostate cancer cells in mice with no evidence of collateral toxicity in normal tissue.

Sumith Kularatne, a graduate student in Purdue’s chemistry department and first author of both papers, compared the targeting molecule to a homing device.

“The molecule acts like a homing device for prostate cancer,” he said. “PSMA, which is found only on prostate cancer cells and tumor blood vessels, acts as the homing signal that the molecule targets. The molecule and its cargo go only to cancerous tissue, leaving healthy tissue unharmed.”

Philip Low, the Ralph C. Corley Distinguished Professor of Biochemistry at Purdue, and graduate student Sumith Kularatne, in foreground, examine the uptake of an imaging agent in prostate cancer cells. Low led a research team that designed a molecule to find and penetrate prostate cancer cells and has created imaging agents and therapeutic drugs that can link to the molecule and be carried with it as cargo. (Purdue University photo/Andrew Hancock)

Once the molecule reaches the PSMA protein, it binds to it. The molecule is designed with a specific shape that fits with the protein like a key to a lock, Kularatne said. The molecule and its cargo are then carried inside the cell with the protein as it goes through its normal cycle.

In 1995 Low developed a similar method to infiltrate cancer cells by attaching treatments to the vitamin folate, which many cancers rapidly consume. This method provided a “Trojan Horse” entry of large treatment molecules that otherwise would not be able to enter cancer cells.

Low was inspired to find a similar way to target prostate cancer, which does not have the same appetite for folate, he said.

A clinical trial of the radioimaging application is expected to begin at the Indiana University Medical Center in the fall through a collaboration between the Purdue Cancer Center and the Indiana University Cancer Center with additional support from Endocyte Inc.

A radioimaging agent linked to the targeting molecule will be injected into prostate cancer patients and pictures will be taken using a special camera that detects radioactivity. The pictures show where the cancer is present to help doctors determine if it has metastasized, or spread, to any other areas of the body. It also will help doctors decide on the best course of treatment, Low said.

There is currently only one radioimaging agent for prostate cancer approved by the Food and Drug Administration.

“The current imaging capabilities available for prostate cancer are very poor,” Low said. “The existing imaging agent is limited because of its large size, which is difficult to get into a solid tumor. Also it seeks out a target located inside the cancer cell and is only able to mark injured cells that are falling apart as opposed to actively growing cancer cells.”

The targeting molecule and radioimaging agent combination designed by Low’s group is more than 150 times smaller than the existing agent and has much easier penetration through a solid tumor to reach all of the cells inside, he said. It also has the advantage of targeting an area of PSMA exposed on the outside of cancer cells.

Already in clinical trials is an optical imaging application that involves attaching a fluorescent dye to the targeting molecule and mixing it with a patient’s blood sample. Circulating prostate cancer cells in the sample fluoresce and are easily measured to help in diagnosing patients with prostate cancer. Researchers also are investigating whether this could be used to evaluate a patient’s response to therapy, Low said.

Low’s research group modeled the targeting molecule after a naturally occurring molecule that strongly binds to PSMA, called DUPA. Several alterations were necessary to create a molecule that fit the needs of a homing device and delivery vehicle, Kularatne said. The team created an area on the molecule that would link to various imaging or therapeutic agents to bring them along as cargo and created a spacer that would stretch the molecule so that its cargo would not keep it from properly fitting into the binding site. The spacer also was designed to improve binding of the targeting molecule to PSMA.

In addition to Low and Kularatne, co-authors of the papers include Endocyte researchers Kevin Wang and Hari-Krishna R. Santhapuram, graduate student in medicinal chemistry Zhigang Zhou, graduate student in chemistry Jun Yang, and professor of medicinal chemistry and molecular pharmacology Carol B. Post.

Low is the chief science officer for Endocyte, a Purdue Research Park-based company that develops receptor-targeted therapeutics for the treatment of cancer and autoimmune diseases. Endocyte holds the license to many of Low’s drug-targeting technologies.

Papers:

Prostate-Specific Membrane Antigen Targeted Imaging and Therapy of Prostate Cancer Using a PSMA Inhibitor as a Homing Ligand
Sumith A. Kularatne, Kevin Wang, Hari-Krishna R. Santhapuram, and Philip S. Low

Design, Synthesis, and Preclinical Evaluation of Prostate-Specific Membrane Antigen Targeted ^99mTc-Radioimaging Agents
Sumith A. Kularatne, Zhigang Zhou, Jun Yang, Carol B. Post, and Philip S. Low

By Elizabeth K. Gardner – Purdue University

Baltimore, MD—Scientists working at the Carnegie Institution’s Department of Embryology, with colleagues, have overturned previous research that identified critical genes for making muscle stem cells. It turns out that the genes that make muscle stem cells in the embryo are surprisingly not needed in adult muscle stem cells to regenerate muscles after injury. The finding challenges the current course of research into muscular dystrophy, muscle injury, and regenerative medicine, which uses stem cells for healing tissues, and it favours using age-matched stem cells for therapy.  The study is published in the June 25 advance on-line edition of Nature.

This cross section of hind limb muscle tissue is from a mouse five days after injury. The uninjured cells are at top and stained red. The blue cells below are regenerating muscles cells. They were labeled with a blue stain and formed from muscle stem cells. Image courtesy Christoph Lepper

Previous studies have shown that two genes Pax3 and Pax7, are essential for making the embryonic and neonatal muscle stem cells in the mouse. Lead researcher Christoph Lepper, a predoctoral fellow in Carnegie’s Chen-Ming Fan’s lab and a Johns Hopkins student, for the first time looked at these two genes in promoting stem cells at varying stages of muscle growth in live mice after birth.

As Christoph explained: “The paired-box genes, Pax3 and Pax7 are involved in the development of the skeletal muscles. It is well established that both genes are needed to produce muscle stem cells in the embryo. A previous student, Alice Chen, studied how these genes are turned on in embryonic muscle stem cells (also published in Nature). I thought that if they are so important in the embryo, they must be important for adult muscle stem cells.  Using genetic tricks, I was able to suppress both genes in the adult muscle stem cells. I was totally surprised to find that the muscle stem cells are normal without them.”

The researchers then looked at whether the same was true upon injury, after which the repair process requires muscle stem cells to make new muscles. For this, they injured the leg muscles between the knee and ankle. They were again surprised that these muscle stem cells, without the two key embryonic muscle stem cell genes, could generate muscles as well as normal muscle stem cells. They even performed a second round of injury and found that the stem cells were still active.

The scientists then wondered when these genes become unnecessary for muscle stem cells to regenerate muscles. It turned out that these embryonic genes are important to muscle stem cell creation up to the first three weeks after birth. What makes the muscle stem cells different after three weeks? The scientist believe that these two embryonic muscle stem cell genes also tell the stem cells to become quiet as the organism matures. After that time is reached, they “hand over” their jobs to a different set of genes. The researchers suggest that since the adult muscle stem cells are only activated when injury occurs (by trauma or exercise), they use a new set of genes from those used during embryonic development, which proceeds without injury. The scientists are eager to find these adult muscle stem cell genes.

“We are just beginning to learn the basics of stem cell biology, and there are many surprises,” remarked Allan Spradling, director of Carnegie’s Department of Embryology. “This work illustrates the importance of carrying out basic research using animal models before rushing into the clinic with half-baked therapies.”

Listen to the scientist in his own words at this link: http://www.ciw.edu/publications_online/embedded_video/stem_cell_surprise.html

Carnegie Institution For Science

HOUSTON – (June 22, 2009) – Researchers at The University of Texas School of Public Health have developed a game for HIV-positive youth, +CLICK, designed to reduce secondary transmission of the virus.

+CLICK. (The University of Texas School of Public Health)

+CLICK was developed by Christine Markham, Ph.D., and Ross Shegog, Ph.D., assistant professors of behavioral sciences. The game’s usability and credibility were assessed by HIV-positive (HIV+) youth at a Texas Children’s Hospital clinic. Results from the study were published in the May issue of AIDS Care.

According to the World Health Organization, adolescents and young adults ages 13-24 account for 40 percent of new HIV infections worldwide and almost half of all HIV infections in the United States. Many HIV+ youth engage in risky sexual behaviors, according to Markham.

“We wanted to create +CLICK so that we could help educate youth on the importance of making proper, healthy decisions to protect their relationships and themselves as well as help to reduce transmission of the HIV virus,” said Markham, lead investigator of the study.

The game was developed as an adjunct to the youths’ traditional clinic-based self-management education.

The small sample size of 32 study participants included 62.5 percent females and 37.5 percent males. Of those participants, 56.2 percent contracted the virus through birth and 43.8 percent became infected through sexual contact.

Markham and Shegog worked with Mary Paul, M.D., associate professor of pediatrics at Baylor College of Medicine, and Amy Leonard, M.P.H., research coordinator at Baylor College of Medicine, to develop the material presented in the interactive lessons.

Replicating a shopping mall, study participants travel through lessons on abstinence, condoms and contraception, and also watch video clips from experts and peers who are also HIV+. +CLICK is designed to target four behaviors: choosing not to have sex; disclosing HIV status to a potential partner; using condoms correctly and consistently; and using an effective method of birth control along with condoms.

Participants were able to play several of the game’s lessons in approximately 15 minutes during their regularly scheduled clinic visits. “Participants were very receptive and enthusiastic about playing the game,” said Leonard. “They also liked that they were able to ask the clinicians questions about what they learned on the lessons.” Credibility of the game was trusted by 93.8 percent of the participants and 84.4 percent of users found the game to be very easy to use and would tell others about +CLICK, according to the study.

A prototype of the game was used for the study. The game, which is in the last stages of development, is tentatively scheduled to be available to the public in approximately six months. In addition, the research team is working to create a similar web-based game that will focus on medication adherence for HIV+ youth.

This study was funded by the Baylor College of Medicine-University of Texas at Houston Center for AIDS Research.

The University of Texas
Health Science Center
At Houston

Vaseline, a known molecule from apples and a gene network encapsulated in algal gelatin are the components of a possible gene therapy which literally gets under the skin. This is what a research group in the Department of Biosystems (D-BSSE) in Basle managed to achieve.

New way to gene therapy: first implant a capsule with a particular gene under the skin, apply skin cream in order to stimulate the gene into action, which expresses an active principle which is able to escape from the capsule. (Image: P. Rüegg/ ETH Zürich)

“An apple a day keeps the doctor away”. This English proverb now has a new meaning. Marc Gitzinger from the research group of Martin Fussenegger, Professor of Biotechnology and Bioengineering Science in the Department of Biosystems (D-BSSE) in Basle, has developed a prototype for gene therapy through the skin. An important part in this is played by phloretin, an antioxidant found in apples which makes cell walls more permeable and is used in cosmetics as an anti-wrinkle agent. The researchers have presented their new therapeutic approach online in the current edition of PNAS.

Capsules and cream

The method of administration sounds very simple: first implant a capsule with a particular gene under the skin and then apply skin cream in order to stimulate the gene into action, which finally expresses an active principle which is able to escape from the capsule in a precise dose.

Fussenegger’s group has managed to do something which sounds like science fiction. The researchers have produced alginate capsules with living cells containing a specially designed genetic network. This network produces the protein SEAP. The capsules were implanted under the skin of test mice which were then coated with an ointment. This skin cream consists of commercial milk fat mixed with phloretin according to a particular formula.

And it worked. Phloretin penetrated the skin, the gel capsules and the cells contained within. As hoped for by the researchers, the antioxidant from the apples reduced the production of protein. With a large dose of phloretin in the cream, the production of SEAP could be stopped altogether.

“When developing the principle we had no particular clinical picture in mind”, emphasised the ETH professor. “We were concentrating on the route of administration through the skin”. A genetic network such as this can also be designed in such a way that when activated correctly, insulin or growth factors are produced. The researcher can imagine that certain metabolic diseases might be treatable by this method. The D-BSSE scientists have already had the method patented and hope that the pharmaceutical industry will be interested in further developing this principle.

Liver spared

This form of gene therapy has several advantages, stressed the ETH professor. It puts no strain on the liver because it has a very local action and phloretin is a molecule which can be found in everyday foodstuffs and undergoes rapid degradation in the body. Furthermore, the network can be precisely controlled and the therapy is well tolerated by the liver, adds Fussenegger. The disadvantage of orally administered therapeutic agents is that the liver, as the detoxifying organ, destroys most of the active agent before it reaches the target site.

Fussenegger is also convinced that implants are well accepted by the public. Implants can be stored in the body for a relatively long time and are easily removed after the end of therapy or in the event of complications.

This new genetic network is a typical example of progress in synthetic biology. Researchers use known and well-characterised biological components to construct artificial networks which in turn are able to produce gene products such as specific proteins. Researchers can also use certain components to make biological switches which in turn allow such systems to be switched on or off.

Reference:

Gitzinger M, Kemmer C, El-Baba MD, Weber W, Fussenegger M. Controlling Transgene Expression in Subcutaneous Implants Using a Skin Lotion Containing the Apple Metabolite Phloretin. PNAS, online publication 22 June 200. doi:10.1073/pnas.0901501106

By Peter Rüegg – ETH Zürich

A discovery by a team of Canadian and American researchers could provide new ways to fight HIV-AIDS. According to a new study published in Nature Medicine, HIV-AIDS could be treated through a combination of targeted chemotherapy and current Highly Active Retroviral (HAART) treatments. This radical new therapy would make it possible to destroy both the viruses circulating in the body as well as those playing hide-and-seek in immune system cells.

(Université de Montréal)

The study was led by Dr. Rafick-Pierre Sékaly, of the Université de Montréal. Dr. Jean-Pierre Routy of the Research Institute of the McGill University Health Centre (RI-MUHC) and scientists from the National Institutes of Health (NIH) and the University of Minnesota in the United States also collaborated on the investigation. To date, anti-AIDS treatments have been stymied by “HIV reservoirs” – immune system cells where the virus hides and where existing HAART treatments cannot reach. The researchers successfully identified the cells where HIV hides and the “stealth” mechanisms that allow the virus to escape existing treatments. This breakthrough opens the way towards innovative therapies that are completely different from current approaches.

“Our results argue in favour of a strategy similar to the one used against leukemia, which is targeted chemotherapy, associated with a targeted immune treatment. This would make it possible to destroy the cells containing a virus, while giving the immune system time to regenerate with healthy cells,” says Dr. Rafick-Pierre Sékaly, a professor at the Université de Montréal, researcher at the Centre Hospitalier de Université de Montréal (CHUM), director of INSERM 743 and scientific director of the Vaccine and Gene Therapy Institute of Florida.

“For the first time, this study proves that the HIV reservoirs are not due to a lack of potency of the antiretroviral drugs, but to the virus hiding inside two different types of long life CD4 memory immune cells,” explains Dr. Jean-Pierre Routy, a hematologist with the MUHC, researcher in infection and immunity at the RI-MUHC and professor of hematology at McGill University. “There are several types of HIV reservoirs, each necessitating a different treatment to eliminate them.”

Nicolas Chomont and Rafick-Pierre Sékaly of the Université de Montréal with McGill University’s Jean-Pierre Routy. (Université de Montréal)

Indeed, once the virus is hidden in these reservoir cells, it becomes dependent on them: if the cell lives, the virus lives, but if the cell dies, so does the virus. As such, destroying these immune cells will allow for the elimination of the resilient or hidden parts of the virus. Existing HAART treatments destroy the viruses circulating in the body, yet cannot reach those hidden in reservoir cells.

“We now have brand-new options to fight HIV,” concludes Nicolas Chomont, a postdoctoral intern at the Université de Montréal’s Department of Microbiology and Immunology and one of the co-authors of this study. “The combination of fundamental and clinical approaches led to amazing results that allow us to elucidate another mystery of this virus of a thousand faces.”

These new therapeutic options will require many more years of research before they are validated and become a reality for patients. However, this study represents an invaluable work plan that will provide a map for many laboratories around the world.

Partners in research
This study was funded by the American Foundation for AIDS Research (amfAR), the National Institutes of Health, the Canadian Institutes of Health Research and the FRSQ-AIDS and Infectious Diseases Network.

About the study
The study, “HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation,” published in Nature Medicine, was coauthored by Rafick-Pierre Sékaly, Elias K. Haddad, Nicolas Chomont, Mohamed El Far, Petronela Ancuta, Lydie Trautmann, Francesco A. Procopio, Bader Yassine-Diab and Geneviève Boucher of the Université de Montréal and Centre Hospitalier de Université de Montréal (CHUM), Jean-Pierre Routy, Mohamed-Rachid Boulassel and Georges Ghattas of the McGill University Health Centre (MUHC) and McGill University, Brenna J. Hill, Daniel C. Douek and Jason M. Brenchley of the National Institutes of Health, U.S.A., and Timothy W. Schacker of the University of Minnesota, U.S.A.

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About the Université de Montréal’s Faculty of Medicine
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Université de Montréal

The next generation of instruments for ground-based telescopes took a leap forward with the development of a new ultra-fast camera that can take 1500 finely exposed images per second even when observing extremely faint objects. The first 240×240 pixel images with the world’s fastest high precision faint light camera were obtained through a collaborative effort between ESO and three French laboratories from the French Centre National de la Recherche Scientifique/Institut National des Sciences de l’Univers (CNRS/INSU). Cameras such as this are key components of the next generation of adaptive optics instruments of Europe’s ground-based astronomy flagship facility, the ESO Very Large Telescope (VLT).

The CCD220 detector at the core of the OCam camera has 240 x 240 pixels and has a readout noise ten times smaller than detectors in current use, making it ideal for the faint light camera systems to be used on the second generation of Very Large Telescope instruments. It was developed by the British manufacturer e2v technologies. Source: ESO

“The performance of this breakthrough camera is without an equivalent anywhere in the world. The camera will enable great leaps forward in many areas of the study of the Universe,” says Norbert Hubin, head of the Adaptive Optics department at ESO. OCam will be part of the second-generation VLT instrument SPHERE. To be installed in 2011, SPHERE will take images of giant exoplanets orbiting nearby stars.

A fast camera such as this is needed as an essential component for the modern adaptive optics instruments used on the largest ground-based telescopes. Telescopes on the ground suffer from the blurring effect induced by atmospheric turbulence. This turbulence causes the stars to twinkle in a way that delights poets, but frustrates astronomers, since it blurs the finest details of the images.

Adaptive optics techniques overcome this major drawback, so that ground-based telescopes can produce images that are as sharp as if taken from space. Adaptive optics is based on real-time corrections computed from images obtained by a special camera working at very high speeds. Nowadays, this means many hundreds of times each second. The new generation instruments require these corrections to be done at an even higher rate, more than one thousand times a second, and this is where OCam is essential.

“The quality of the adaptive optics correction strongly depends on the speed of the camera and on its sensitivity,” says Philippe Feautrier from the LAOG, France, who coordinated the whole project. “But these are a priori contradictory requirements, as in general the faster a camera is, the less sensitive it is.” This is why cameras normally used for very high frame-rate movies require extremely powerful illumination, which is of course not an option for astronomical cameras.

OCam and its CCD220 detector, developed by the British manufacturer e2v technologies, solve this dilemma, by being not only the fastest available, but also very sensitive, making a significant jump in performance for such cameras. Because of imperfect operation of any physical electronic devices, a CCD camera suffers from so-called readout noise. OCam has a readout noise ten times smaller than the detectors currently used on the VLT, making it much more sensitive and able to take pictures of the faintest of sources.

OCam is the world’s fastest high precision faint light camera. Developed in Europe, the camera is highly sensitive and able to take 1500 images per second. OCam has been specially designed and built by a team of French engineers from LAM, LAOG and the OHP and uses the CCD220 detector developed by e2v technologies. The technology developed with OCam has been transferred to ESO for use with the second generation instruments of ESO’s Very Large Telescope. Source: ESO

“Thanks to this technology, all the new generation instruments of ESO’s Very Large Telescope will be able to produce the best possible images, with an unequalled sharpness,” declares Jean-Luc Gach, from the Laboratoire d’Astrophysique de Marseille, France, who led the team that built the camera.

“Plans are now underway to develop the adaptive optics detectors required for ESO’s planned 42-metre European Extremely Large Telescope, together with our research partners and the industry,” says Hubin.

Using sensitive detectors developed in the UK, with a control system developed in France, with German and Spanish participation, OCam is truly an outcome of a European collaboration that will be widely used and commercially produced.

More information

The three French laboratories involved are the Laboratoire d’Astrophysique de Marseille (LAM/INSU/CNRS, Université de Provence; Observatoire Astronomique de Marseille Provence), the Laboratoire d’Astrophysique de Grenoble (LAOG/INSU/CNRS, Université Joseph Fourier; Observatoire des Sciences de l’Univers de Grenoble), and the Observatoire de Haute Provence (OHP/INSU/CNRS; Observatoire Astronomique de Marseille Provence).

OCam and the CCD220 are the result of five years work, financed by the European commission, ESO and CNRS-INSU, within the OPTICON project of the 6th Research and Development Framework Programme of the European Union. The development of the CCD220, supervised by ESO, was undertaken by the British company e2v technologies, one of the world leaders in the manufacture of scientific detectors. The corresponding OPTICON activity was led by the Laboratoire d’Astrophysique de Grenoble, France. The OCam camera was built by a team of French engineers from the Laboratoire d’Astrophysique de Marseille, the Laboratoire d’Astrophysique de Grenoble and the Observatoire de Haute Provence. In order to secure the continuation of this successful project a new OPTICON project started in June 2009 as part of the 7th Research and Development Framework Programme of the European Union with the same partners, with the aim of developing a detector and camera with even more powerful functionality for use with an artificial laser star. This development is necessary to ensure the image quality of the future 42-metre European Extremely Large Telescope.

ESO, the European Southern Observatory, is the foremost intergovernmental astronomy organisation in Europe and the world’s most productive astronomical observatory. It is supported by 14 countries: Austria, Belgium, the Czech Republic, Denmark, France, Finland, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, Switzerland and the United Kingdom. ESO carries out an ambitious programme focused on the design, construction and operation of powerful ground-based observing facilities enabling astronomers to make important scientific discoveries. ESO also plays a leading role in promoting and organising cooperation in astronomical research. ESO operates three unique world-class observing sites in Chile: La Silla, Paranal and Chajnantor. At Paranal, ESO operates the Very Large Telescope, the world’s most advanced visible-light astronomical observatory. ESO is the European partner of a revolutionary astronomical telescope ALMA, the largest astronomical project in existence. ESO is currently planning a 42-metre European Extremely Large optical/near-infrared Telescope, the E-ELT, which will become “the world’s biggest eye on the sky”.

ESO European Organisation for Astronomical Research in the Southern Hemisphere

C.S. Mott Children’s Hospital National Poll on Children’s Health finds that in areas where no helmet laws exist, half of children never wear helmets while riding bikes.

ANN ARBOR, Mich.—Studies have shown wearing a helmet while riding a bicycle reduces one’s risk of death by more than 50 percent, yet every three days, a child in the United States is killed while riding a bicycle, and every day at least 100 children are treated in emergency rooms due to bicycle-related head injuries.

Source: University of Michigan Health System

A report released today by the University of Michigan C.S. Mott Children’s Hospital National Poll on Children’s Health reveals that in areas where no bicycle helmet laws exist, nearly one-half of children, ages 4 – 17, never wear a helmet.

“These statistics underscore the importance of helmet laws to help prevent death and injury from children not wearing helmets while riding their bikes,” says Matthew M. Davis, M.D., director of the National Poll on Children’s Health. “Yet only twenty one states have helmet use laws for children.”

Data from the National Highway Traffic Safety Administration indicate universal bicycle helmet use by children, ages 4 – 15, would prevent about 40,000 head injuries and about 50,000 scalp and face injuries every year.

While the poll shows helmet use is better in areas where helmet laws exist (54 percent of parents report their children always wear a helmet while riding a bike), the poll also measured adults’ awareness of helmet laws in their communities and whether or not they would support new laws if none existed.

Forty-one percent of parents said they were unsure about helmet use laws in their communities. Overall, 86 percent of respondents would support helmet laws for children in their communities.

The poll also shows that other barriers to helmet use exist for some parents whether or not laws exist in their areas. Among parents who report their child never wears a helmet, 32 percent believe they are too expensive. One in two children in the lowest income families making less than $30,000 per year never wear a helmet.

As children age, self concept and image may play a role in their decisions about whether or not they will wear a helmet. Among children who never use helmets, 59 percent of parents report that their children do not like wearing helmets.

“Wearing a bicycle helmet is essentially a health behavior,” Davis says. “It is not yet a fashion statement. For many kids – especially older kids – there is a tension between this healthy behavior and being seen as cool or acceptable by their peers. There is a challenge here for health care providers and public health officials to communicate that wearing a helmet is actually the cool thing to do besides being the healthy thing to do.”

The poll also finds:

• . 78 percent of parents report children ages 4 – 17 ride bicycles.
• . 27 percent never wear their helmets while riding their bikes.
• . Among children ages 4 – 11, 53 percent always wear helmet while riding bikes, while only 29 percent of children ages 12 – 17 always wear helmets while riding bikes.
• . In states and communities that have bicycle laws, 54 percent of children 14-17 always wear a helmet, while only 24 percent of children always wear a helmet in places without a bicycle helmet law for children.

“To try to increase helmet use across the country, there are at least three ways we can proceed. One way is to pass more helmet laws,” Davis says. “There is also a group of parents out there who really want their children to wear helmets but can’t afford them. We should be better at sharing information about the very successful state and local programs that provide free or cheap helmets for kids. The third opportunity here is to change how families view helmets in terms of how important it is to use them regularly. That is going to be perhaps the toughest because it involves communicating the benefits of the health behavior and really trying to make a longstanding difference in the attitudes of parents and in the communities that may not yet be on board with the use of bicycle helmets.”

Resources:

C.S. Mott Children’s Hospital National Poll on Children’s Health: www.med.umich.edu/mott/npch

National Highway Traffic Safety Administration:

Bicycle Helmet Use Laws: www.nhtsa.dot.gov/people/injury/TSFLaws/PDFs/810886.pdf
Cyclist safety facts: www-nrd.nhtsa.dot.gov/Pubs/810986.pdf

American College of Emergency Physicians: www.acep.org/pressroom.aspx?LinkIdentifier=id&id=25986&fid=3496&Mo=No

Clinical Pediatrics

Bicycle-Related Injuries Among Children and Adolescents in the United States: http://cpj.sagepub.com/cgi/content/abstract/48/2/166

Methodology: For its report, the National Poll on Children’s Health used data from a national online survey conducted in January 2009 in collaboration with Knowledge Networks, Inc. The survey was administered to a random sample of 2,125 adults, ages 18 and older, who are a part of Knowledge Network’s online KnowledgePanel®. The sample was subsequently weighted to reflect U.S. population figures from the U.S. Census Bureau. About three-fourths of the sample included households with children. The margin of sampling error is plus or minus 1 to 9 percentage points. For results based on subgroups, the margin of error is higher.

To learn more about Knowledge Networks, visit www.knowledgenetworks.com.

Purpose/Funding: The C.S. Mott Children’s Hospital National Poll on Children’s Health – funded by the Department of Pediatrics and Communicable Diseases and part of the CHEAR Unit at the U-M Health System – is designed to measure major health care issues and trends for U.S. children.

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Written by Jessica Soulliere – University of Michigan Health System