Findings by UT Southwestern Medical Center researchers may suggest new strategies for successful donor adult stem cell transplants in patients with blood cancers such as leukemia, lymphoma and myeloma.
The study, published Aug. 5 in Cell Stem Cell, showed for the first time that adult blood stem cells can be regulated to overcome an immune response that leads to transplant rejection. It also opens up further studies in stem cell immunology, said Dr. Chengcheng “Alec” Zhang, assistant professor of physiology and developmental biology at UT Southwestern and senior author of the study.
“We speculate that a common mechanism exists to regulate immune inhibitors in different types of stem cells,” he said.
Nearly 1 million people in the U.S. are living with or in remission from blood cancers; more than 135,000 are expected to be diagnosed this year. Blood and bone marrow stem cell transplants are needed when a patient’s body stops making enough healthy blood cells.
In this current study, UT researchers developed a culture “cocktail” that successfully supported adult blood stem cells from humans and from mice, and found that they express immune inhibitors on their surfaces that protect them from immune attack. Using the increased number of cultured blood stem cells, the scientists were able to overcome the protein barrier that alerts the immune system to foreign material and significantly repopulated healthy cells in the rodent transplantation recipients.
“We revealed that the expansion of adult blood stem cells through culture and an increase in cell surface expression of an immune molecule are the keys for this to happen,” Dr. Zhang said.
Source: UT Southwestern Medical Center
Published on 4th August 2011
Got lots of fast food restaurants and other outlets that sell junk food in your neighborhood? Then your teen is more likely to nosh regularly on burgers and fries and wash them down with a soda.
That is the unpalatable finding of a new study from the UCLA Center for Health Policy Research that examined the effect of higher concentrations of less healthy food outlets on adolescent junk food consumption.
The upshot? Nearly three-quarters of California teenagers live or go to school in neighborhoods that are crowded with fast food restaurants and other outlets that sell unhealthy food — convenience stores, liquor stores, dollar stores and pharmacies — relative to the number of healthier food outlets, such as grocery stores, produce vendors and farmers markets. And unsurprisingly, teens who live or go to school in such neighborhoods are more likely to drink soda and eat fast food.
Research has shown that the consumption of fast food and soda has been linked to taking in excess calories and can contribute to diabetes and obesity.
“You are what you eat. You are, also, where you live,” said Susan Babey, a study co-author and a senior research scientist at the center. “And if you live in a place where there’s a fast food restaurant or convenience store on every block, with few healthier alternatives, you are likely to eat more junk.”
Many more unhealthy outlets
Using both the 2007 California Health Interview Survey and InfoUSA, a 2007 database of U.S. businesses, the study’s authors calculated a Home and School Retail Food Environment Index, which measured the number of less healthy food outlets relative to the number of healthier outlets surrounding the homes and schools of California teens, and compared that measurement to teen junk food consumption.
They found that the average California teen has more than seven times as many junk food outlets near home and school as healthier food outlets.
And teens in more unhealthy neighborhoods were 17 percent more likely to drink soda every day and 18 percent more likely to eat fast food at least twice a week than their peers in healthier neighborhoods.
“It is a travesty that our kids have better access to liquor stores and other unhealthy food outlets than a grocery store,” said Robert K. Ross, M.D., president and CEO of the California Endowment, which funded the study. “We have put our children and youth in harm’s way, and they are paying the price for our carelessness. If nothing is done, this will be the first generation to live shorter lives than their parents.”
Few counties immune
The research showed that few counties, whether rural or urban, were immune from the unhealthy effects of junk-food outlet density. In San Benito, Sutter, Merced and Fresno counties, more than 70 percent of teens consume at least one soda per day. In Tulare, Riverside, Ventura and Kern counties, more than 55 percent of teens eat fast food at least twice a week. In total, 13 counties across California had Home and School Retail Food Environment Index scores of more than 8 points — an indication of a relatively unhealthy food environment.
The authors recommended a number of policy options to improve the food environments where teens live and go to school, including better zoning, especially around schools, and farm-to-school programs that bring fresh produce into school cafeterias. They also noted that better incentives were needed to bring healthy food outlets, such as farmers markets and grocery stores, into underserved neighborhoods.
“The research shows that how we plan and zone our communities has a real impact on our health and quality of life,” Babey said. “Policymakers need to take this into account when deciding whether to zone a new grocery store or a fast food restaurant. Hopefully, they will make the healthy choice.”
Source: University of California – Los Angeles.
Published on 29th July 2011
Charles Stanish at excavation site in Taraco (Credit: Image courtesy of University of California – Los Angeles)
Warfare, triggered by political conflict between the fifth century B.C. and the first century A.D., likely shaped the development of the first settlement that would classify as a civilization in the Titicaca basin of southern Peru, a new UCLA study suggests.
Charles Stanish, director of UCLA’s Cotsen Institute of Archaeology, and Abigail Levine, a UCLA graduate student in anthropology, used archaeological evidence from the basin, home to a number of thriving and complex early societies during the first millennium B.C., to trace the evolution of two larger, dominant states in the region: Taraco, along the Ramis River, and Pukara, in the grassland pampas.
“This study is part of a larger, worldwide comparative research effort to define the factors that gave rise to the first societies that developed public buildings, widespread religions and regional political systems — or basically characteristics associated with ancient states or what is colloquially known as ‘civilization,'” said Stanish, who is also a professor of anthropology at UCLA. “War, regional trade and specialized labor are the three factors that keep coming up as predecessors to civilization.”
The findings appear online in the latest edition of Proceedings of the National Academy of Sciences.
Conducted between 2004 and 2006, the authors’ excavations in Taraco unearthed signs of a massive fire that raged sometime during the first century A.D., reducing much of the state to ash and architectural rubble. The authors compared artifacts dating from before and after the fire and concluded that agriculture, pottery and the obsidian industry, all of which had flourished in the state, greatly declined after the fire.
Based on the range and extent of the destruction and the lack of evidence supporting reconstruction efforts, the authors suggest that the fire was a result of war, not of an accident or a ritual.
Iconographic evidence of conflict in regional stone-work, textiles and pottery suggests that the destruction of Taraco had been preceded by several centuries of raids. This includes depictions of trophy heads and people dressed in feline pelts cutting off heads, among other evidence.
Because the downfall of Taraco, which was home to roughly 5,000 people, coincided with the rise of neighboring Pukara as a dominant political force in the region, the authors suggest that warfare between the states may have led to the raids, shaping the early political landscape of the northern Titicaca basin.
Inhabited between 500 B.C. and 200 A.D., Pukara was the first regional population center in the Andes highlands. During its peak, it covered more than 2 square kilometer and housed approximately 10,000 residents, including bureaucrats, priests, artisans, farmers, herders and possibly warriors.
The civilization’s ruins include impressive monolithic sculptures with a variety of geometric, zoomorphic and anthropomorphic images, plus intricate, multi-colored pottery in a variety of ritual and domestic forms.
War appears to have played a similar civilizing role in Mesoamerica, as well as Mesopotamia, Stanish said. To further test his theories on the origins of civilization, Stanish will begin a new project next year at a Neolithic site in Armenia.
Source: University of California – Los Angeles.
Published on 29th July 2011
An array of piezoelectrically modulated resistive memory (PRM) cells is shown being studied in an optical microscope. (Georgia Tech Photo: Gary Meek)
The piezotronic memory devices developed by Wang and graduate student Wenzhuo Wu take advantage of the fact that piezoelectric materials like zinc oxide produce a charge potential when they are mechanically deformed or otherwise put under strain. These PRM devices use the piezoelectric charge created by the deformation to control the current flowing through the zinc oxide nanowires that are at the heart of the devices — the basic principle of piezotronics. The charge creates polarity in the nanowires — and increases the electrical resistance much like gate voltage in a conventional transistor.
“We are replacing the application of an external voltage with the production of an internal voltage,” Wang explained. “Because zinc oxide is both piezoelectric and semiconducting, when you strain the material with a mechanical action, you create a piezopotential. This piezopotential tunes the charge transport across the interface — instead of controlling channel width as in conventional field effect transistors.”
The mechanical strain could come from mechanical activities as diverse as signing a name with a pen, the motion of an actuator on a nanorobot, or biological activities of the human body such as a heart beating.
“We control the charge flow across the interface using strain,” Wang explained. “If you have no strain, the charge flows normally. But if you apply a strain, the resulting voltage builds a barrier that controls the flow.”
The piezotronic switching affects current flowing in just one direction, depending on whether the strain is tensile or compressive. That means the memory stored in the piezotronic devices has both a sign and a magnitude. The information in this memory can be read, processed and stored through conventional electronic means.
Taking advantage of large-scale fabrication techniques for zinc oxide nanowire arrays, the Georgia Tech researchers have built non-volatile resistive switching memories for use as a storage medium. They have shown that these piezotronic devices can be written, that information can be read from them, and that they can be erased for re-use. About 20 of the arrays have been built so far for testing.
The zinc oxide nanowires, which are about 500 nanometers in diameter and about 50 microns long, are produced with a physical vapor deposition process that uses a high-temperature furnace. The resulting structures are then treated with oxygen plasma to reduce the number of crystalline defects — which helps to control their conductivity. The arrays are then transferred to a flexible substrate.
“The switching voltage is tunable, depending on the number of oxygen vacancies in the structure,” Wang said. “The more defects you quench away with the oxygen plasma, the larger the voltage that will be required to drive current flow.”
The piezotronic memory cells operate at low frequencies, which are appropriate for the kind of biologically-generated signals they will record, Wang said.
These piezotronic memory elements provide another component needed for fabricating complete self-powered nanoelectromechanical systems (NEMS) on a single chip. Wang’s research team has already demonstrated other key elements such as nanogenerators, sensors and wireless transmitters.
“We are taking another step toward the goal of self-powered complete systems,” Wang said. “The challenge now is to make them small enough to be integrated onto a single chip. We believe these systems will solve important problems in people’s lives.”
Wang believes this new memory will become increasingly important as devices become more closely connected to individual human activities. The ability to build these devices on flexible substrates means they can be used in the body — and with other electronic devices now being built on materials that are not traditional silicon.
“As computers and other electronic devices become more personalized and human-like, we will need to develop new types of signals, interfacing mechanical actions to electronics,” he said. “Piezoelectric materials provide the most sensitive way to translate these gentle mechanical actions into electronic signals that can be used by electronic devices.”
Source: Georgia Institute of Technology
Published on 28th July 2011
Preschool children consumed nearly twice as many vegetables and 11 percent fewer calories over the course of a day when researchers from Penn State added pureed vegetables to the children’s favorite foods.
“Childhood obesity rates are on the rise, and at the same time children are not eating the recommended amount of vegetables,” said Barbara Rolls, professor of nutritional sciences and holder of the Helen A. Guthrie chair in nutritional sciences in Penn State’s College of Health and Human Development. “Vegetables have been shown to help lower calorie intake. The problem is getting kids to eat enough vegetables.”
In their study, the researchers served vegetable-enhanced entrées to 39 children between the ages of 3 and 6 on three separate days. They tested three familiar foods — zucchini bread for breakfast, pasta with a tomato-based sauce for lunch and chicken noodle casserole for dinner. The team modified the standard recipes for these foods by adding a variety of puréed vegetables to reduce the calories in the entrées by 15 percent and 25 percent.
“We incorporated several vegetables into the dishes, including broccoli, cauliflower, zucchini, tomatoes and squash,” said Maureen Spill, a post-doctoral fellow in nutritional sciences and the study’s lead author. “We were pleased to find that the children found the vegetable-enhanced versions to be equally acceptable to the standard recipes.”
According to Spill, the children ate the same weight of food regardless of the vegetable content of the entrées. And when they ate the vegetable-enhanced entrées as opposed to the standard-recipe entrées, their daily vegetable intake nearly doubled while their calorie intake decreased by 11 percent. The team’s findings are online in the American Journal of Clinical Nutrition.
Rolls and Penn State colleagues Alexandria Blatt, a recent doctoral degree recipient and Liane Roe, a researcher, both in nutritional sciences, found similar results when they served vegetable-enhanced entrées to adults. That work appeared in the April 2011 issue of the American Journal of Clinical Nutrition.
“Regarding children, some people argue that hiding vegetables in foods is deceptive and that doing so suggests that whole vegetables are not acceptable,” said Rolls. “But I don’t agree. Parents modify recipes all the time. For example, it is well-accepted that applesauce can be used to replace oil in cake batter.”
Spill noted that serving vegetables both within entrées and as side dishes is a great way to increase daily vegetable intake even more. “Preparing vegetable-enhanced entrées is a technique that should be used with other strategies, such as providing vegetables as snacks and side dishes. Together these strategies can substantially increase children’s vegetable intake while also teaching them to like vegetables.”
The National Institute of Diabetes and Digestive and Kidney Diseases funded this research. Other authors on the paper include Leann Birch, distinguished professor of human development and family studies, and Liane Roe, researcher in nutritional sciences.
Source: Pennsylvania State University
Published on 28th July 2011
Researchers at the Georgia Institute of Technology have designed a multiple-compartment gel capsule that could be used to simultaneously deliver drugs of different types. The researchers used a simple “one-pot” method to prepare the hydrogel capsules, which measure less than one micron.
The capsule’s structure — hollow except for polymer chains tethered to the interior of the shell — provides spatially-segregated compartments that make it a good candidate for multi-drug encapsulation and release strategies. The microcapsule could be used to simultaneously deliver distinct drugs by filling the core of the capsule with hydrophilic drugs and trapping hydrophobic drugs within nanoparticles assembled from the polymer chains.
“We have demonstrated that we can make a fairly complex multi-component delivery vehicle using a relatively straightforward and scalable synthesis,” said L. Andrew Lyon, a professor in the School of Chemistry and Biochemistry at Georgia Tech. “Additional research will need to be conducted to determine how they would best be loaded, delivered and triggered to release the drugs.”
Details of the microcapsule synthesis procedure were published online on July 5, 2011 in the journal Macromolecular Rapid Communications.
Lyon and Xiaobo Hu, a former visiting scholar at Georgia Tech, created the microcapsules. As a graduate student at the Research Institute of Materials Science at the South China University of Technology, Hu is co-advised by Lyon and Zhen Tong of the South China University of Technology. Funding for this research was provided to Hu by the China Scholarship Council.
The researchers began the two-step, one-pot synthesis procedure by forming core particles from a temperature-sensitive polymer called poly(N-isopropylacrylamide). To create a dissolvable core, they formed polymer chains from the particles without a cross-linking agent. This resulted in an aggregated collection of polymer chains with temperature-dependent stability.
“The polymer comprising the core particles is known for undergoing chain transfer reactions that add cross-linking points without the presence of a cross-linking agent, so we initiated the polymerization using a redox method with ammonium persulfate and N,N,N’,N’-tetramethylethylenediamine. This ensured those side chain transfer reactions did not occur, which allowed us to create a truly dissolvable core,” explained Lyon.
For the second step in the procedure, Lyon and Hu added a cross-linking agent to a polymer called poly(N-isopropylmethacrylamide) to create a shell around the aggregated polymer chains. The researchers conducted this step under conditions that would allow any core-associated polymer chains that interacted with the shell during synthesis to undergo chain transfer and become grafted to the interior of the shell.
Cooling the microcapsule exploited the temperature sensitivities of the polymers. The shell swelled with water and expanded to its stable size, while the free-floating polymer chains in the center of the capsule diffused out of the core, leaving behind an empty space. Any chains that stuck to the shell during its synthesis remained. Because the chains control the interaction between the particles they store and their surroundings, the tethered chains can act as hydrophobic drug carriers.
Compared to delivering a single drug, co-delivery of multiple drugs has several potential advantages, including synergistic effects, suppressed drug resistance and the ability to tune the relative dosage of various drugs. The future optimization of these microcapsules may allow simultaneous delivery of distinct classes of drugs for the treatment of diseases like cancer, which is often treated using combination chemotherapy.
Source: Georgia Institute of Technology
Published on 13th July 2011
Purdue associate professor of biological sciences Zhao-Qing Luo, foreground, and graduate student Yunhao Tan identified a new way in which bacteria modify healthy cells during infection. Shown on the computer screen are cells infected with a mutant strain of the bacteria Legionella pneumophila used in their research. (Credit: Purdue University photo/Mark Simons)
Purdue University biologists identified a new way in which bacteria hijack healthy cells during infection, which could provide a target for new antibiotics.
Zhao-Qing Luo, the associate professor of biological sciences who led the study, said the team discovered a new enzyme used by the bacterium Legionella pneumophila – which causes Legionnaires’ disease – to control its host cell in order to take up residence.
“Legionnaires’ disease is a severe form of pneumonia, and this finding could lead to the design of a new therapy that saves lives,” Luo said. “At the same time it also provides great insight into a general mechanism of both bacterial infection and cell signaling events in higher organisms including humans.”
Successful infection by Legionella pneumophila requires the delivery of hundreds of proteins into the host cells that alter various functions to turn the naturally hostile environment into one tailor-made for bacterial replication. These proteins tap into existing communication processes within the cells in which an external signal, such as a hormone, triggers a cascade of slight modifications to proteins that eventually turns on a gene that changes the cell’s behavior, he said.
“Pathogens are successful because they know how information in our cells is relayed and they amplify some signals and block others in order to evade the immune system and keep the cell from defending itself,” Luo said. “Despite our understanding of this, we do not know much about how the proteins delivered by the bacteria accomplish this – how they work. This time we were able to pinpoint an enzyme and see how it disrupted and manipulated a specific signaling pathway in order to create a better environment for itself.”
The signaling pathway involved was only recently identified, and the discovery by Luo and graduate student Yunhao Tan also provides a key insight into its process. A paper detailing their National Institutes of Health-funded work is published online in the current issue of the journal Nature.
The signaling pathway involves a new form of protein modification called AMPylation in order to relay instructions to change cell behavior and has been found to be used by almost all organisms, Luo said.
The bacterial enzyme discovered by the Purdue team, named SidD, reverses or stops the AMPylation process, he said.
“It had not been known before if the AMPylation signaling process was reversible or if it was regulated by specific enzymes,” Luo said. “Now we know that it is, and we have a more complete picture that will allow us to use it as a scientific tool to learn more about complex cellular processes. By being able to turn the signaling on and off, we can control different activities and detect mechanisms we wouldn’t see under normal physiological conditions.”
The bacterium affects the host cell’s functions differently during different phases of the infection process, tapping into signaling pathways to turn on and off certain natural cellular activities. SidD stops the AMPylation process four hours after the start of infection in order to reverse an earlier modification that would be detrimental to the cell if left in place, he said.
“During its process of infection, the bacteria can trigger reactions that can lead to the death of the host cell,” Luo said. “Of course this is not in the best interest of the bacteria because it would no longer be able to replicate and continue infection, so it has evolved mechanisms to neutralize such reactions and keep the host cell alive.”
Luo said further investigation of the structure and function of the SidD enzyme is needed to better understand its role in the infection process and its involvement in other cellular processes.
“The more we can learn about an infectious agent, the better equipped we will be to design a therapy to fight it,” he said. “Before a new antibiotic therapy can be created, we must understand the enzyme enough to find chemicals to inhibit its activity. Further, because the bacteria have coevolved with us for millions of years, they provide some of the best tools for us to understand the intricacy of cellular processes.”
Luo plans to further study SidD and investigate other proteins used by Legionella pneumophila bacteria.
Source: Purdue University
Published on 13th July 2011
Engineers at UC San Diego are mimicking the movement of bird wings to help improve the maneuverability of unmanned aerial vehicles (UAVs).
UAVs are often used for surveillance of a fixed target in military and civilian applications. In order to observe a stationary target, a fixed wing UAV must remain airborne over the object, thus expending
energy for propulsion and reducing operational time. In addition, the aircraft may need to loiter at significant altitudes to avoid detection, and thus require complex sensors to observe the target far below. Rotary wing aircraft may be able to land on a perch for surveillance, but are generally less efficient for cruising flight than a fixed wing solution. A fixed wing aircraft capable of spot landing on a perch (top of a pole, building, fence, etc.) would be an ideal solution capable of efficient cruising and versatile landing for longer surveillance missions. Because the target is nearby, simple sensors could be used onboard the perched aircraft.
The problem of perching has already been solved by nature. Birds routinely land on small surfaces, using wing morphing and flapping techniques. The UC San Diego engineers, led by mechanical and aerospace engineering professor Tom Bewley and graduate student Kim Wright, analyzed in slow motion several videos of birds landing to generate a working hypotheses for how wing morphing and flapping can be used for spot landing.
“One of the key behaviors observed in the birds was their use of wing sweep for pitch control in both forward flight and stalled landing approaches,” she said. “Birds can move their wings in a myriad of ways, providing a level of aerodynamic control that is unmatched by UAVs,” Wright said.
To verify their hypotheses, Wright and her team built a small remote controlled UAV with variable wing sweep and tested it using computer modeling, and an onboard microcontroller as a flight data recorder. Their initial testing validated the concept of using wing sweep for pitch control of the aircraft.
The biologically-inspired aircraft design is similar in scale to the birds the engineers observed (barn owl, hawks, large parrots, crows) and has similar wing loading and airfoil characteristics. The fuselage and tail surfaces of the prototype UAV were primarily constructed from balsa wood and foam using standard hobby aircraft construction techniques. The wings were formed using composite construction utilizing carbon fiber, fiberglass, high density foam, and rip stop nylon. Carbon fiber tubing was used for the shoulder joint structure, and fiberglass reinforcement was used in heavily stressed areas on the fuselage.
Future research could address combining wing twist, flapping, or other wing morphing aspects of the perching problem that UAVs currently have. Being able to perch UAVs autonomously on features in the environment (tree tops, buildings, telephone poles, etc…), and then to take off again as required, is an immensely valuable and significantly increases mission duration.
“Combining these aspects into a fully actuated, intelligent UAV would be the ultimate goal,’ said Wright, who nabbed first place for this research under a poster titled “Investigating the use of wing sweep for pitch control of a small unmanned air vehicle,” during the Jacobs School’s Research Expo 2011. “A small UAV that could maneuver and land like a bird would be a valuable tool for surveillance and search and rescue. This project has brought the aerospace community a small step closer to that goal.”
UC San Diego aerospace and mechanical engineering graduate student Kim Wright studied the flight and movement of various types of birds to design a prototype UAV.(Credit: Image courtesy of University of California, San Diego)
Wright said the future of UAVs is diverse. UAVs are quickly becoming popular tools for the armed forces, but there are also a myriad of civilian applications, which are rapidly developing, such as wildfire monitoring, search and rescue, and traffic observation.
“The technology is out there, and once federal aviation regulations are able to safely accommodate UAVs, I believe we will start seeing a lot more of them,” she said.
Source: University of California, San Diego
Published on 10th June 2011
A clinical trial for a new technology to diagnose and treat prostate cancer marks the first time Purdue University has directed the entire pathway of a therapeutic product from early research to patient treatment.
Therapeutics developed from research at the university are typically licensed to a pharmaceutical
company that takes it through the pipeline of preclinical studies, manufacturing and then clinical trials, said Timothy Ratliff, the Robert Wallace Miller Director of the Purdue University Center for Cancer Research who is leading the project.
“Purdue has a long history of research that has been the basis of life-saving treatments, and now we’ve shown that we can take a therapeutic drug or technology through every step from concept to clinical trial,” Ratliff said. “By managing the process all the way through to a clinical trial, the scientists behind the advancement maintain control of its development as it goes through the trials and get the satisfaction of seeing their discovery impact patients and improve lives.”
Eventually most therapeutic treatments developed at Purdue will have to be sold to a company in order to be manufactured and widely distributed. The further along in the process a product is, the better it is for the university and the state, he said.
“The value of a potential treatment increases as it makes its way through each step of the process, which means the scientists and the university will receive more revenue to continue the research process,” he said. “Managing the design, development and testing also means more money stays in the state and more Indiana workers are involved in the process.”
The ongoing clinical trial is testing the combination of a radioimaging agent and a prostate cancer-targeting molecule developed by Philip Low, Purdue’s Ralph C. Corley Distinguished Professor of Chemistry.
Low and his research team designed a targeting molecule that seeks out and attaches to prostate-specific membrane antigen, or PSMA, a protein that is found on the outer membrane of the cells of more than 90 percent of all prostate cancers.
“The targeting molecule is in essence a homing device for prostate cancer that can link to a variety of therapeutic agents, including imaging agents and drugs,” said Low, who also is a member of the Purdue Center for Cancer Research. “PSMA acts as the homing signal for the molecule, which binds to the protein and then is carried inside the cancer cell. The molecule and its cargo go only to cancerous tissue and leave healthy tissue unharmed.”
Ratliff and Low are working with scientists and physicians at the Indiana University School of Medicine and the Indiana University Melvin and Bren Simon Cancer Center to perform the clinical trial.
The clinical trial is the first to test the technology in humans and will evaluate the targeting molecule’s ability to recognize prostate cancer and deliver an imaging agent. The patients included in the study have prostate cancer that can be seen by computerized tomography scan, or CT scan, so that it can easily be determined how well the radioimaging agent is reaching the cancerous tissue.
“If the new technology picks up the cancer that we know and can see, we will have more confidence that it can also pick up cancer that can’t be seen by a CT scan,” Low said. “If the trial goes well, we will begin a new imaging trial to determine if we can image prostate cancer well enough to help physicians stage the disease.”
Dr. Thomas Gardner, the urologist at the Indiana University Melvin and Bren Simon Cancer Center who treats the patients involved in the trial, said the technology may help reduce unnecessary procedures and allow other treatments to be given earlier.
“Treatment of prostate cancer depends on how far we think the disease has progressed, or its stage,” Gardner said. “If the cancer is confined to the prostate, we aggressively treat the organ itself, but if it has spread beyond the prostate a more systemic approach is necessary. It doesn’t make sense to put someone through focused treatments of their prostate and the side effects that go along with it if they will need to go through systemic treatments. Better detection would allow physicians to know that the cancer had spread at a much earlier point.”
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, so it 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 can much more easily penetrate a solid tumor to reach all of the cells inside, he said.
Three patients currently have been treated in the clinical trial that will include around 25 patients. The trial should be complete in about a year, Low said.
Dr. Song-Chu Ko, in the Department of Radiation Oncology at the IU School of Medicine and a member of the IU Melvin and Bren Simon Cancer Center, leads the clinical trial. In addition to Gardner and Ko, the IU team also includes Noah Hahn of the Department of Hematology and Oncology, Peter Johnstone of the Department of Radiation Oncology, James Fletcher of the Department of Nuclear Medicine, Michael Koch of the Department of Urology and Gary Hutchins of the Department of Radiology.
Source: Purdue University
Published on 7th July 2011
The chemically cleared leaf of Heteromeles arbutifolia shows its major and minor veins.(Credit: Christine Scoffoni/UCLA Ecology and Evolutionary Biology)
The size of leaves can vary by a factor of 1,000 across plant species, but until now, the reason why has remained a mystery. A new study by an international team of scientists led by UCLA life scientists goes a long way toward solving it.
In research federally funded by the National Science Foundation, the biologists found that smaller leaves are structurally and physiologically better adapted to dry soil because of their distinct vein systems.
The research will be published in an upcoming print issue of the journal Plant Physiology and is currently available in the journal’s online edition.
“A hike in dry areas, such as the Santa Monica Mountains, proves that leaves can be small. But if you are in the tropical forest, many leaves are enormous,” said Lawren Sack, a UCLA professor of ecology and evolutionary biology and senior author of the research.
This biogeographic trend — smaller leaves in drier areas — may be the best recognized in plant ecology, true at both the local and global scales, but it had evaded direct explanation, Sack said.
Sack and his research team focused on deciphering the meaning of the huge diversity in the patterns of veins across plants. They found that small leaves’ major veins — those you can see with the naked eye — are spaced more closely together and are of greater length, relative to the leaf’s size, than those of larger leaves.
This redundancy of major veins, the researchers say, protects the leaves from the effects of embolism — bubbles that form in their “water pipes” during drought — because it provides alternate routes for water to flow around vein blockages.
“Even with strong drought that forms embolism in the veins, a small leaf maintains function in its vein system and can keep functioning for water transport,” Sack said.
“Unlike people, plants don’t seem to have a complex hierarchy of needs — give them sun, water and nutrients, and they will be happy,” said Christine Scoffoni, a UCLA doctoral student in the department of ecology and evolutionary biology and lead author of the research. “But when one of these three fundamental resources becomes scarce, the plant will have to find a way to cope with it or die, because there is no escape. Coping with drought can be a strong selective factor on leaf form, especially on size and their venation.”
“When we ask our students in plant physiology class why plants need water, their first answer is for growth,” Sack said. “They are amazed to learn that the bulk of the water used by a plant is actually to make up for the water lost through transpiration, which would otherwise dry out the leaves. When the leaves open the small pores on their surface, the stomata, to capture carbon dioxide for photosynthesis, water is lost to the dry atmosphere. To stay moist inside, the plants need to replace the water lost by evaporation.”
To do this, plants need to maintain the continuity of water in their “pipe delivery system,” even as water is being pulled up by the leaves to replace water that has been lost to the air. This places tension on the water in the pipe system, known as the xylem, which runs through the roots and stem and into the leaf veins. And that continuity is challenged by dry soil, Sack explained.
“The less water in the soil, the more the leaves have to pull to get some out, so stronger tension starts building in the plant’s pipes,” Scoffoni said. “At a certain level of tension, an air bubble is pulled in from outside, blocking the flow of water. One way for a plant to withstand drought is to tolerate many of these embolisms.”
Having more major vein routes by which water can flow around the air bubble provides this ability. Smaller leaves, possessing more major veins spaced closely together in a given square centimeter, have this ability, Sack said.
To test this idea, the UCLA team collaborated with professor Hervé Cochard from France’s University of Clermont-Ferrand and a member of the Institut National de Recherche Agronomique, to construct three-dimensional computer models of leaves’ venation systems. They then simulated the impact of embolism on water transport for leaves of different sizes and vein architectures.
The biologists found a distinct difference in function between the major veins, which tend to show a branching pattern, and the minor veins, which form a grid embedded within the leaf and make up most of the leaf’s total vein length. Blocking the major veins had a huge impact on leaf function — but one that could be remedied by having additional, redundant major veins.
Scoffoni likens the major veins to a superhighway and the minor veins to sinuous city roads, where embolism is like an accident causing a major slowdown.
“If an air bubble forms in the leaf’s water pathway, the more alternate highways the vein system has to offer, the less the leaf will be affected by these accidents,” Scoffoni said.
The UCLA biologists — including co-authors Michael Rawls, an undergraduate student, and Athena McKown, a postdoctoral scholar in ecology and evolutionary biology — tested diverse leaves from very wet and dry areas, all planted near the UCLA campus. The leaves fit the pattern: The biologists found that smaller leaves indeed had more tightly packed major veins and were more resistant to the effects of embolism in the major veins. The were better able to maintain water transport, even during extreme drying, Sack said.
While the trend of smaller leaves in drier areas is so striking that it appears in textbooks, and the trend is used by scientists to estimate rainfall in the distant past from the size of fossil leaves, the mechanism had never been explained. The previous theory proposed an indirect linkage, arguing that smaller leaves have a thinner layer of still air around them, which allows them to cool off faster in hotter places. According to this theory, because many dry places are also warmer, this might lead to the evolution of smaller leaves in such environments.
As Sack noted, however, “this is indirect and does not explain the trend of smaller leaves in drier places when temperature is similar. This trend appears across species, and even within individual species, when plants are grown in moister and drier soil.”
The team expects that this mechanism, which points to a new role of vein architecture and leaf size in drought tolerance, will generate new interest in plant diversity and adaptation to environments. In addition, Sack said, the discovery shows that even very well-known biogeographic trends are open to new scientific explanation.
Source: University of California – Los Angeles
Published on 7th July 2011