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  • richardmitnick 1:43 pm on March 25, 2015 Permalink | Reply
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    From NOVA: “Stems Cells Finally Deliver, But Not on Their Original Promise” 

    PBS NOVA

    NOVA

    25 Mar 2015
    Carrie Arnold

    To scientists, stem cells represent the potential of the human body to heal itself. The cells are our body’s wide-eyed kindergarteners—they have the potential to do pretty much anything, from helping us obtain oxygen, digest food, or pump our blood. That flexibility has given scientists hope that they can coax stem cells to differentiate into and replace those damaged by illness.

    Almost immediately after scientists learned how to isolate stem cells from human embryos, the excitement was palpable. In the lab, they had already been coaxed into becoming heart muscle, bone marrow, and kidney cells. Entire companies were founded to translate therapies into clinical trials. Nearly 20 years on, though, only a handful of therapies using stem cells have been approved. Not quite the revolution we had envisioned back in 1998.

    But stem cells have delivered on another promise, one that is already having a broad impact on medical science. In their investigations into the potential therapeutic functions of stem cells, scientists have discovered another way to help those suffering from neurodegenerative and other incurable diseases. With stem cells, researchers can study how these diseases begin and even test the efficacy of drugs on cells from the very people they’re intended to treat.

    Getting to this point hasn’t been easy. Research into pluripotent stem cells, the most promising type, has faced a number of scientific and ethical hurdles. They were most readily found in developing embryos, but in 1995, Congress passed a bill that eliminated funding on embryonic stem cells. Since adult humans don’t have pluripotent stem cells, researchers were stuck.

    That changed in 2006, when Japanese scientist Shinya Yamanaka developed a way to create stem cells from a skin biopsy. Yamanaka’s process to create induced pluripotent stem cells (iPS cells) won him and his colleague John Gurdon a Nobel Prize in 2012. After years of setbacks, the stem cell revolution was back on.

    1
    A cluster of iPS cells has been induced to express neural proteins, which have been tagged with fluorescent antibodies.

    Biomedical scientists in fields from cancer to heart disease have turned to iPS cells in their research. But the technique has been especially popular among scientists studying neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS) for two main reasons: One, since symptoms of these diseases don’t develop until rather late in the disease process, scientists haven’t had much knowledge about the early stages. IPS cells changed that by allowing scientists to study the very early stages of the disorder. And two, they provide novel ways of testing new drugs and potentially even personalizing treatment options.

    “It’s creating a sea change,” says Jeanne Loring, a stem cell biologist at the Scripps Research Institute in San Diego. “There will be tools available that have never been available before, and it will completely change drug development.”

    Beyond Animal Models

    Long before scientists knew that stem cells existed, they relied on animals to model diseases. Through careful breeding and, later, genetic engineering, researchers have developed rats, mice, fruit flies, roundworms, and other animals that display symptoms of the illness in question. Animal models remain useful, but they’re not perfect. While the biology of these animals often mimics humans’, they aren’t identical, and although some animals might share many of the overt symptoms of human illness, scientists can’t be sure that they experience the disease in the same way humans do.

    “Mouse models are useful research tools, but they rarely capture the disease process,” says Rick Livesey, a biologist at the University of Cambridge in the U.K. Many neurodegenerative diseases, like Alzheimer’s, he says, are perfect examples of the shortcomings of animal models. “No other species of animal actually gets Alzheimer’s disease, so any animal model is a compromise.”

    As a result, many drugs that seemed to be effective in animal models showed no benefit in humans. A study published in Alzheimer’s Research and Therapy in June 2014 estimated that 99.9% of Alzheimer’s clinical trials ended in failure, costing both money and lives. Scientists like Ole Isacson, a neuroscientist at Harvard University who studies Parkinson’s disease, were eager for a method that would let them investigate illnesses in a patient’s own cells, eliminating the need for expensive and imperfect animal models.

    Stem cells appeared to offer that potential, but when Congress banned federal funding in 1995 for research on embryos—and thus the development of new stem cell lines—scientists found their work had ground to a halt. As many researchers in the U.S. fretted over the future of stem cell research, scientists in Japan were developing a technique which would eliminate the need for embryonic stem cells. What’s more, it would allow researchers to create stem cells from the individuals who were suffering from the diseases they were studying.

    Cells in the body are able to specialize by turning on some sets of genes and switching off others. Every cell has a complete copy of the DNA, it’s just packed away in deep storage where the cell can’t easily access it. Yamanaka, the Nobel laureate, knew that finding the key to this storage locker and unpacking it could potentially turn any specialized cell back into a pluripotent stem cell. He focused in on a group of 24 genes that were active only in embryonic stem cells. If he could get adult, specialized cells to translate these genes into proteins, then they should revert to stem cells. Yamanaka settled on fibroblast cells as the source of iPS cells since these are easily obtained with a skin biopsy.

    Rather than trying to switch these genes back on, a difficult and time-consuming task, Yamanaka instead engineered a retrovirus to carry copies of these 24 genes to mouse fibroblast cells. Since many retroviruses insert their own genetic material into the genomes of the cells they infect, Yamanaka only had to deliver the virus once. All successive generations of cells inherited those 24 genes. Yamanaka first grew the fibroblasts in a dish, then infected them with his engineered retrovirus. Over repeated experiments, Yamanaka was able to narrow the suite of required genes from 24 down to just four.

    The process was far from perfect—it took several weeks to create the stem cells, and only around 0.01%–0.1% of the fibroblasts were actually converted to stem cells. But after Yamanaka published his results in Cell in 2006, scientists quickly began perfecting the procedure and developing other techniques. To say they have been successful would be an understatement. “The technology is so good now that I have the undergraduates in my lab doing the reprogramming,” Loring says.

    Accelerating Disease

    When he heard of Yamanaka’s discovery, Isacson, the Harvard neuroscientist studying Parkinson’s disease, had been using fetal neurons to try to replace diseased and dying neurons. Isacson realized “very quickly” that iPS cells could yield new discoveries about Parkinson’s. At the time, scientists were trying to determine exactly when the disease process started. It wasn’t easy. A person has to lose around 70% of their dopamine neurons before the first sign of movement disorder appears and Parkinson’s can be diagnosed. By that point, it’s too late to reverse that damage, a problem that is found in many if not all neurodegenerative diseases. Isacson wanted to know what was causing the neurons to die.

    Together with the National Institute of Neurological Disorders and Stroke consortium on iPS cells, Isacson obtained fibroblasts from patients with genetic mutations linked to Parkinson’s. Then, he reprogrammed these cells to become the specific type of neurons affected by Parkinson’s disease. “To our surprise, in the very strong hereditary forms of disease, we found that cells showed very strong signs of distress in the dish, even though they were newborn cells,” Isacson says.

    These experiments, published in Science Translational Medicine in 2012, showed that the disease process in Parkinson’s started far earlier than scientists expected. The distressed, differentiated neurons Isacson saw under the microscope were still just a few weeks old. People generally didn’t start showing symptoms for Parkinson’s disease until middle age or beyond.

    2
    A clump of stem cells, seen here in green

    Isacson and his colleagues then tried to determine what was different between different cells with different mutations. The cells showed the most distress in their mitochondria, the parts of the cell that act as power plants by creating energy from oxygen and glucose. How that distress manifested, though, varied slightly depending on which mutation the patient carried. Neurons derived from an individual with a mutation in the LRRK2 gene consumed lower than expected amounts of oxygen, whereas the neurons derived from those carrying a mutation in PINK1 had much higher oxygen consumption. Neurons with these mutations were also more susceptible to a type of cellular damage known as oxidative stress.

    After exposing both groups of cells to a variety of environmental toxins, such as oligomycin and valinomycin, both of which affect mitochondria, Isacson and colleagues attempted to rescue the cells by using several compounds that had been found effective in animal models. Both the LRRK2 and the PINK1 cells responded well to the antioxidant coenzyme Q10, but had very different responses to the immunosuppressant drug rapamycin. Whereas LRRK2 showed beneficial responses to rapamycin, the PINK1 cells did not.

    To Isacson, the different responses were profoundly important. “Most drugs don’t become blockbusters because they don’t work for everyone. Trials start too late, and they don’t know the genetic background of the patient,” Isacson says. He believes that iPS cells will one day help researchers match specific treatments with specific genotypes. There may not be a single blockbuster that can treat Parkinson’s, but there may be several drugs that make meaningful differences in patients’ lives.

    Cancer biologists have already begun culturing tumor cells and testing anti-cancer drugs before giving these medications to patients, and biologists studying neurodegenerative disease hope that iPS cells will one day allow them to do something similar for their patients. Scientists studying ALS have recently taken a step in that direction, using iPS cells to create motor neurons from fibroblasts of people carrying a mutation in the C9orf72 gene, the most common genetic cause of ALS. In a recent paper in Neuron, the scientists identified a small molecule which blocked the formation of toxic proteins caused by this mutation in cultured motor neurons.

    Adding More Dimensions

    It’s one thing to identify early disease in iPS cells, but these cells are generally obtained from people who have been diagnosed. At that point, it’s too late, in a way; drugs may be much less likely to work in later stages of the disease. To make many potential drugs more effective, the disease has to be diagnosed much, much earlier. Recent work by Harvard University stem cell biologist Rudolph Tanzi and colleagues may have taken a step in that direction, also using iPS cells.

    Doo Yeon Kim, Tanzi’s co-author, had grown frustrated with iPS cell models of neurodegenerative disease. The cell cultures were liquid, and the cells could only grow in a thin, two-dimensional layer. The brain, however, was more gel-like, and existed in three dimensions. So Kim created a 3D gel matrix on which the researchers grew human neural stem cells that carried extra copies of two genes—one which codes for amyloid precursor protein and another for presenilin 1, both of which were previously discovered in Tanzi’s lab—which are linked to familial forms of Alzheimer’s disease.

    After six weeks, the cells contained high levels of the harmful beta-amyloid protein as well as large numbers of toxic neurofibrillary tangles that damage and kill neurons. Both of these proteins had been found at high levels in the neurons of individuals who had died from Alzheimer’s disease, but researchers didn’t know for certain which protein built up first and which was more central to the disease process. Further experiments revealed that drugs preventing the formation of amyloid proteins also prevented the formation of neurofibrillary tangles, indicating that amyloid proteins likely formed first during Alzheimer’s disease.

    “When you stop amyloid, you stop cell death,” Tanzi says. Amyloid begins to build up long before people show signs of altered cognition, and Tanzi believes that drugs which stop amyloid or prevent the buildup of neurofibrillary tangles could prevent Alzheimer’s before it starts.

    The results were hailed in the media as a “major breakthrough,” although Larry Goldstein, a neuroscientist at the University of California, San Diego, takes a more nuanced perspective. “It’s a nice paper and an important step forward, but things got overblown. I don’t know that I would use the word ‘breakthrough’ because these, like all results, often have a very long history to them,” Goldstein says.

    The scientists who spoke with NOVA Next about iPS cells noted that the field is moving forward at a remarkable clip, but they all talked at length about the issues that still remain. One of the largest revolves around differences between the age of the iPS cells and the age of the humans who develop these neurodegenerative diseases. Although scientists are working with neurons that are technically “mature,” they are nonetheless only weeks or months old—far from the several decades that the sufferers of neurodegenerative diseases have. Since aging remains the strongest risk factor for developing these diseases, neuroscientists worry that some disease pathology might be missed in such young cells. “Is it possible to study a disease that takes 70 years to develop in a person using cells that have grown for just a few months in a dish?” Livesey asks.

    So far, the answer has been a tentative yes. Some scientists have begun to devise different strategies to accelerate the aging process in the lab so researchers don’t have to wait several decades before they develop their answers. Lorenz Studer, director of the Center for Stem Cell Biology at the Sloan-Kettering Institute, uses the protein that causes progeria, a disorder of extreme premature aging, to successfully age neurons derived from iPS cells from Parkinson’s disease patients.

    Robert Lanza, a stem cell biologist at Advanced Cell Technology, takes another approach, aging cells by taking small amounts of mature neurons and growing them up in a new dish. “Each time you do this, you are forcing the cells to divide,” Lanza says. “And cells can only divide so many times before they reach senescence and die.” This process, Lanza believes, will mimic aging. He has also been experimenting with stressing the cells to promote premature aging.

    All of these techniques, Livesey believes, will allow scientists to study which aspects of the aging process—such as number of cell divisions and different types of environmental stressors—affect neurodegenerative diseases and how they do so. Adding to the complexity of the experimental system will improve the results that come out at the end. “You can only capture as much biology in iPS cells as you plug into it in the beginning,” Livesey says.

    But as Isacson and Loring’s work, has shown, even very young cells can show hallmarks of neurodegenerative diseases. “If a disease has a genetic cause, if there’s an actual change in DNA, you should be able to find something in those iPS cells that is different,” Loring says.

    For these experiments and others, scientists have been relying on iPS cells derived from individuals with hereditary or familial forms of neurodegenerative disease. These individuals, however, only represent about 5–15% of individuals with neurodegenerative disease; the vast majority of neurodegenerative diseases is sporadic and has no known genetic cause. Scientists believe that environmental factors may play a much larger role in the onset of these forms of neurodegenerative disease.

    That heterogeneity means it’s not yet clear whether the iPS cells from individuals with hereditary forms of disease are a good model for what happens in sporadic disease. Although the resulting symptoms may be the same, different forms of disease may use the same biological pathways to end up in the same place. Isacson is in the process of identifying the range of genes and proteins that are altered in iPS cells that carry Parkinson’s disease mutations. He intends to determine whether any of these pathways are also disturbed in sporadically occurring Parkinson’s disease to pinpoint any similarities in both forms of disease.

    Livesey’s lab just received a large grant to study people with an early onset, sporadic form of Alzheimer’s. “Although sporadic Alzheimer’s disease isn’t caused by a mutation in a single gene, the condition is still strongly heritable. The environment, obviously, has an important role, but so does genetics,” Livesey says.

    Because the disease starts earlier in these individuals, researchers believe that it has a larger genetic link than other forms of sporadic Alzheimer’s disease, which will make it easier to identify any genetic or biological abnormalities. Livesey hopes that bridging sporadic and hereditary forms of Alzheimer’s disease will allow researchers to reach stronger conclusions using iPS cells.

    Though it will be years before any new drugs come out of Livesey’s stem cell studies—or any other stem cell study for that matter—the technology has nonetheless allowed scientists to refine their understanding of these and other diseases. And, scientists believe, this is just the start. “There are an endless series of discoveries that can be made in the next few decades,” Isacson says.

    Image credit: Ole Isacson, McLean Hospital and Harvard Medical School/NINDS

    See the full article here.

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    NOVA is the highest rated science series on television and the most watched documentary series on public television. It is also one of television’s most acclaimed series, having won every major television award, most of them many times over.

     
  • richardmitnick 12:56 pm on March 25, 2015 Permalink | Reply
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    From phys.org: “Research team develops acoustic topological insulator idea to allow for hiding from sonar” 

    physdotorg
    phys.org

    March 25, 2015
    Bob Yirka

    1
    Around the bend. An acoustic topological insulator would guide sound waves around its edges, as shown in this simulation. Credit: Z. Yang et al., Phys. Rev. Lett. (2015)

    A team of researchers working in Singapore has come up with what they believe is a way to apply a topologic[al] insulator to an object to prevent sound waves from being bounced back and detected by a source. They have published their work in the journal Physical Review Letters.

    Scientists have developed ways to coat materials with other materials to causes electric current to remain on the surface, preventing damage to sensitive parts inside—such coatings are called topological insulators and are generally based on causing less scattering and creating a band gap. In this new effort, the research team has expanded on that idea to bring a similar result for insulating objects from sound waves.

    To make a topological insulator work against sonar would involve creating a coating or cover that could cause sound waves to propagate around an object (instead of scattering) rather than allowing them to be bounced back to a receiver. To make that happen, the researchers envision a cover made up of a lattice of spinning metal cylinders, each of which would be surrounded by a bit of fluid which would itself be contained within an acoustically transparent shell. The same fluid would be used to fill the spaces between the cylinders, but it would not move. Because of the spinning movement inside, a vortex would be created in the fluid that surrounds the cylinders. In this setup, sound waves would not be able to move through the center of the structure due to a periodic pattern that would produce a sonic band gap—but the rotating fluid around the center would allow for causing propagation to occur in a predefined direction—the edge states, the team notes, could guide sound waves with high precision. A submarine covered with such an insulator would be invisible to sonar because sound waves sent in its direction would be routed in a direction away from where they came from, preventing them from bouncing back to the source.

    The work thus far by the team is purely theoretical, but they suggest there is no reason to believe it would not work in practice. The most difficult part they note, would be dealing with irregular “bumps” on a surface, which could throw off the propagation if not handled properly.

    See the full article here.

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    About Phys.org in 100 Words

    Phys.org™ (formerly Physorg.com) is a leading web-based science, research and technology news service which covers a full range of topics. These include physics, earth science, medicine, nanotechnology, electronics, space, biology, chemistry, computer sciences, engineering, mathematics and other sciences and technologies. Launched in 2004, Phys.org’s readership has grown steadily to include 1.75 million scientists, researchers, and engineers every month. Phys.org publishes approximately 100 quality articles every day, offering some of the most comprehensive coverage of sci-tech developments world-wide. Quancast 2009 includes Phys.org in its list of the Global Top 2,000 Websites. Phys.org community members enjoy access to many personalized features such as social networking, a personal home page set-up, RSS/XML feeds, article comments and ranking, the ability to save favorite articles, a daily newsletter, and other options.

     
  • richardmitnick 11:47 am on March 25, 2015 Permalink | Reply
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    From UW: “UW scientists build a nanolaser using a single atomic sheet” 

    U Washington

    University of Washington

    March 23, 2015
    Jennifer Langston

    1
    The ultra-thin semiconductor, which is about 100,000 times thinner than a human hair, stretches across the top of the photonic cavity.U of Washington

    University of Washington scientists have built a new nanometer-sized laser — using the thinnest semiconductor available today — that is energy efficient, easy to build and compatible with existing electronics.

    Lasers play essential roles in countless technologies, from medical therapies to metal cutters to electronic gadgets. But to meet modern needs in computation, communications, imaging and sensing, scientists are striving to create ever-smaller laser systems that also consume less energy.

    The UW nanolaser, developed in collaboration with Stanford University, uses a tungsten-based semiconductor only three atoms thick as the “gain material” that emits light. The technology is described in a paper published in the March 16 online edition of Nature.

    “This is a recently discovered, new type of semiconductor which is very thin and emits light efficiently,” said Sanfeng Wu, lead author and a UW doctoral candidate in physics. “Researchers are making transistors, light-emitting diodes, and solar cells based on this material because of its properties. And now, nanolasers.”

    Nanolasers — which are so small they can’t be seen with the eye — have the potential to be used in a wide range of applications from next-generation computing to implantable microchips that monitor health problems. But nanolasers so far haven’t strayed far from the research lab.

    Other nanolaser designs use gain materials that are either much thicker or that are embedded in the structure of the cavity that captures light. That makes them difficult to build and to integrate with modern electrical circuits and computing technologies.

    The UW version, instead, uses a flat sheet that can be placed directly on top of a commonly used optical cavity, a tiny cave that confines and intensifies light. The ultrathin nature of the semiconductor — made from a single layer of a tungsten-based molecule — yields efficient coordination between the two key components of the laser.

    The UW nanolaser requires only 27 nanowatts to kickstart its beam, which means it is very energy efficient.

    Other advantages of the UW team’s nanolaser are that it can be easily fabricated, and it can potentially work with silicon components common in modern electronics. Using a separate atomic sheet as the gain material offers versatility and the opportunity to more easily manipulate its properties.

    “You can think of it as the difference between a cell phone where the SIM card is embedded into the phone versus one that’s removable,” said co-author Arka Majumdar, UW assistant professor of electrical engineering and of physics.

    “When you’re working with other materials, your gain medium is embedded and you can’t change it. In our nanolasers, you can take the monolayer out or put it back, and it’s much easier to change around,” he said.

    2
    This emission map of the nano-device shows the light is confined by and emitted from the photonic cavity.U of Washington

    The researchers hope this and other recent innovations will enable them to produce an electrically-driven nanolaser that could open the door to using light, rather than electrons, to transfer information between computer chips and boards.

    The current process can cause systems to overheat and wastes power, so companies such as Facebook, Oracle, HP, Google and Intel with massive data centers are keenly interested in more energy-efficient solutions.

    Using photons rather than electrons to transfer that information would consume less energy and could enable next-generation computing that breaks current bandwidth and power limitations. The recently proven UW nanolaser technology is one step toward making optical computing and short distance optical communication a reality.

    “We all want to make devices run faster with less energy consumption, so we need new technologies,” said co-author Xiaodong Xu, UW associate professor of materials science and engineering and of physics. “The real innovation in this new approach of ours, compared to the old nanolasers, is that we’re able to have scalability and more controls.”

    Still, there’s more work to be done in the near future, Xu said. Next steps include investigating photon statistics to establish the coherent properties of the laser’s light.

    Co-authors are John Schaibley of the UW, Liefeng Feng of the UW and Tianjin University in China, Sonia Buckley and Jelena Vuckovic of Stanford University, Jiaqiang Yan and David G. Mandrus of Oak Ridge National Laboratory and the University of Tennessee, Fariba Hatami of Humboldt University in Berlin and Wang Yao of the University of Hong Kong.

    Primary funding came from the Air Force Office of Scientific Research. Other funders include the National Science Foundation, the state of Washington through the Clean Energy Institute, the Presidential Early Award for Scientists and Engineers administered through the Office of Naval Research, the U.S. Department of Energy, and the European Commission.

    For more information, contact Xu at xuxd@uw.edu and Majumdar at arka@uw.edu.

    See the full article here.

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    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.

    So what defines us — the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
  • richardmitnick 11:37 am on March 24, 2015 Permalink | Reply
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    From Rockefeller: “Chemical tag marks future microRNAs for processing, study shows” 

    Rockefeller U bloc

    Rockefeller University

    March 24, 2015
    Zach Veilleux | 212-327-8982

    1
    Molecular sorting machine: Scientists found the enzyme METTL3 (green) tags a particular sequence within RNA molecules destined to become gene-regulating microRNAs. While this happens within cells’ nuclei (blue), METTL3 is also found outside the nucleus in cells’ cytoplasm, as shown above.

    Just as two DNA strands naturally arrange themselves into a helix, DNA’s molecular cousin RNA can form hairpin-like loops. But unlike DNA, which has a single job, RNA can play many parts — including acting as a precursor for small molecules that block the activity of genes. These small RNA molecules must be trimmed from long hairpin-loop structures, raising a question: How do cells know which RNA loops need to be processed this way and which don’t?

    New research at Rockefeller University, published March 18 in Nature, reveals how cells sort out the loops meant to encode small RNAs, known as microRNAs, by tagging them with a chemical group. Because microRNAs help control processes throughout the body, this discovery has wide-ranging implications for development, health and disease, including cancer, the entry point for this research.

    “Work in our lab and elsewhere has shown changes in levels of microRNAs in a number of cancers. To better understand how and why this happens, we needed to first answer a more basic question and take a closer look at how cells normally identify and process microRNAs,” says study author Sohail Tavazoie, Leon Hess Associate Professor, Senior Attending Physician and head of the Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology. “Claudio Alarcón, a research associate in my lab, has discovered that cells can increase or decrease microRNAs by using a specific chemical tag.”

    Long known as the intermediary between DNA and proteins, RNA has turned out to be a versatile molecule. Scientists have discovered a number of RNA molecules, including microRNAs that regulate gene expression. MicroRNAs are encoded into the genome as DNA, then transcribed into hairpin loop RNA molecules, known as primary microRNAs. These loops are then clipped to generate microRNA precursors.

    To figure out how cells know which hairpin loops to start trimming, Alarcón set out to look for modifications cells might make to the RNA molecules that are destined to become microRNAs. Using bioinformatics software, he scanned for unusual patterns in the unprocessed RNA sequences. The sequence GGAC, code for the bases guanine-guanine-adenine-cytosine, stood out because it appeared with surprising frequency in the unprocessed primary microRNAs. GGAC, in turn, led the researchers to an enzyme known as METTL3, which tags the GGAC segments with a chemical marker, a methyl group, at a particular spot on the adenine.

    “Once we arrived at METTL3, everything made sense. The methyl in adenosines (m6A tag) is the most common known RNA modification. METTL3 is known to contribute to stabilizing and processing messenger RNA, which is transcribed from DNA, but it is suspected of doing much more,” Alarcón says. “Now, we have evidence for a third role: the processing of primary microRNAs.”

    In series of experiments, the researchers confirmed the importance of methyl tagging, finding high levels of it near all types of unprocessed microRNAs, suggesting it is a generic mark associated with these molecules. When they reduced expression of METTL3, unprocessed primary microRNAs accumulated, indicating that the enzyme’s tagging action was important to the process. And, working in cell culture and in biochemical systems, they found primary microRNAs were processed much more efficiently in the presence of the methyl tags than without them.

    “Cells can remove these tags, as well as add them, so these experiments have identified a switch that can be used to ramp up or tamp down microRNA levels, and as a result, alter gene expression,” Tavazoie says. “Not only do we see abnormalities in microRNAs in cancer, levels of METTL3 can be altered as well, which suggests this pathway is could govern cancer progression.”

    See the full article here.

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    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 11:21 am on March 24, 2015 Permalink | Reply
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    From Nautilus: “What a 9,000-Year-Old Spruce Tree Taught Me” 

    Nautilus

    Nautilus

    March 19, 2015
    Rachel Sussman

    I had little idea of what I would discover when I set out to find and photograph the oldest living things in the world. I expected that researching, traveling, and photographing would stretch my perspective, and force me to learn a lot of science: biology, genetics, chemistry, geology, and so on. But what I didn’t expect to learn was that sometimes the right person for a scientific endeavor is an artist.

    The Oldest Living Things project was motivated not by a narrow interest or a traditional scientific question, but by the idea of something called deep time. Deep time is not a precise demarcation in the way that geologic eras and cosmological epochs are. Rather, it’s a framework in which to consider timescales too long for our shallow, physical experience, and too big for our brains to process meaningfully. And why should they be able to? The earliest modern humans had a life expectancy of around 32 years. What evolutionary need would they have had to comprehend what 10,000 years felt like? What I wanted to do was to find or forge something relatable, something to help process and internalize deep time in a meaningful way: to feel expanses of time that we were not designed to feel.

    2
    Antarctic moss: This 5,500-year-old moss bank lives right around the corner from where Ernest Shackleton’s aptly named Endurance Expedition was marooned 100 years ago on Elephant Island, Antarctica.

    When I first had my “light bulb” moment conceiving the Oldest Living Things—which I would eventually publish as a book in 2014—I thought I would find an evolutionary biologist to partner with me. After all, I was an artist with a background in photography whose highest science qualification was 11th grade physics. It hadn’t occurred to me that scientists might declare themselves unqualified for such a broad project.

    After a meeting in September of 2006 with an Assistant Curator at the New York Botanical Garden in the Bronx, I realized that the Oldest Living Things was, in a sense, at odds with scientific specialization. A bryologist might spend his or her career studying one species of moss, or even a single feature or genetic mutation of that moss. In comparison, by the time I’d finished the project, I’d researched 2 domains, 3 kingdoms, 12 classes, 21 orders, 31 families, and 39 species of living things, studied by mycologists, bryologists, astrobiologists, marine biologists, dendrochronologists, and climatologists, to name but a few. And while there are many studies on cell aging and death, there is not an established area of study that looks at longevity across species per se. So instead of partnering with a scientific overseer, I was going to have to step into that role myself.

    3
    Medusa kelp in Hercules Bay: This image made at South Georgia in the Antarctic Convergence is not of a specific ancient organism, but rather speaks to the idea of a landscape as a window into deep time.

    My first task was to begin to curate a collection of organisms to photograph, each a minimum of 2,000 years of age. However, aside from some helpful old-tree lists, there was no such compendium of ancient lives already in existence. This in itself spoke to the fact that I was wandering outside the lines of traditional scientific methodologies. A lot of creative Google searching ensued, as well as reading published scientific research papers and reaching out to authors. The list changed and grew over the years, with new organisms being added even as the book went to print. “New” old organisms were discovered during that time, such as the Siberian Actinobacteria, and others had their ages downgraded, as was the case when the 13,000-year-old box huckleberry in Pennsylvania lost about 5,000 years with the insight of updated glaciation data.

    To qualify for inclusion, each organism must have gone through at least 2,000 years of continuous life as an individual. I selected 2,000 years as my minimum age specifically to draw attention to the gentleman’s agreement of what “year zero” means. In other words, 2000 years serves both as an all-too-human start date, as well as the baseline age of my subjects. The requirement of endurance on an individual level was an important consideration, because we all innately relate to the idea of self. This was a purposeful anthropomorphization that would further imbue the organisms with a reflective quality in which we could glimpse ourselves.

    But once I started digging into the science, things were not so tidy. While unitary organisms such as a single tree are not hard to keep a handle on, things like “clonal colonies” are trickier. Sometimes referred to as “vegetative growth” or “self-propagating,” these individuals are able to generate new clones of themselves, as opposed to reproducing sexually like flowering plants do. They create new shoots, stems, or roots without the introduction of new outside genetic material, so that the new growth is genetically identical to—and part of—the original organism. This process can continue indefinitely, or for as long as the environment allows. This is what is meant when it’s said that clones are theoretically immortal.

    If I were a scientist, grouping unitary and clonal organisms together under the umbrella of “continuously living” would likely raise eyebrows, as this is simply too wide a view to produce a clean outcome. But this idiosyncratic taxonomy is something that I chose to do as an artist, leading to an idiosyncratic taxonomy. Collectively, its members live in some of the world’s harshest conditions, uniquely adapted to extreme temperatures, low moisture and nutrient availability, and high altitudes that would leave others bereft. Many, instead of exhibiting fast or robust growth, exhibit quite the opposite: slow and steady. They gracefully weather adversity, bear witness to long expanses of time, and make the most of difficult situations. As a result, we can’t help but infuse this ancient crew with sought-after human traits like patience and wisdom.

    Over the years I packed up my medium-format film camera again and again, eventually landing on every continent, as I went searching for 5,500-year-old moss in Antarctica, a 2,000-year-old brain coral in Tobago, an 80,000-year-old Aspen colony in Utah, a 2,000-year-old primitive Welwitschia in Namibia, and a 43,600-year-old shrub in Tasmania that’s the last of its kind on the planet, to name but a few. Scientists were more than willing to support my cause. I was sometimes invited to join them on their fieldwork expeditions, such as hunting lichens in Greenland or scuba diving amidst the seagrass meadows stretching between two Spanish Mediterranean islands. Sometimes they agreed to meet me on site and guide me to their subjects: the Palmer’s Oak in Riverside, California, the Baobab trees of South Africa, and the alien-looking llareta in Chile.

    4
    Welwitschia: The Welwitschia is a primitive, cone-bearing plant living only in parts of coastal Namibia and Angola where moisture from the sea meets the desert.

    Other times I was sent maps and directions and GPS coordinates and sent out on my own. Once I was handed a branch snapped off of a propagated sapling in a research garden by a conservation biologist, who instructed me to match the leaf shape with that of the clonal eucalyptus I was in search of. I set out from Perth and drove south a few hours in search of the more than 6,000-year-old Meelup Mallee, which survived a road bulldozed through its center and nearly succumbed to a parking lot before its importance was discovered, just in the nick of time. Guided by roadside markers and the relocated parking area, I took out the branch and dodged through thorny underbrush in the unremitting midday sun in search of my tree. Eventually I found a match to the leaf shape and structure—the Meelup Mallee stood just where I was told to look for it.

    Finally, there were times when there was no scientific connection to be made and I had to depend on cultural signposts. In Sicily, I learned of a legend describing how a queen got caught in a severe thunderstorm en route to Mount Etna. She and 100 of her knights—and, presumably, their horses—all took shelter under the expansive canopy of a certain chestnut tree sometime between 1035 and 1715. The so-called Chestnut of 100 Horses has pride of place in the community, and has long been protected by a fence after a gentleman attempted to grill sausages inside the tree and nearly burnt it down. I heard that story directly from the gatekeeper, Alfio, who allowed me enter on my visits to the site in 2010 and 2012. Likewise, on Crete, Sicily’s Mediterranean neighbor, an ancient olive keeps the town of Ano Vouves on the map. Branches are still culled from it to make wreathes to adorn the winning athletes at the Olympics. The tree is hollow, so it cannot be cored, but if the tree is in fact the 3,000 years it’s claimed to be, it would have already been 200 years old at the time of the first Games in Greece, in 776 B.C.E.

    Over the years, I discovered much that was beyond imagination. My favorite statistic in the whole project came from map lichens (Rhizocarpon geographicum) in Greenland that grow only one centimeter every 100 years—something both perfectly relatable and utterly foreign. Continents are drifting away from one another faster than that. Then there were the stromatolites in Western Australia, bound cyanobacteria combined with non-living sediments, allowing them to straddle biologic and geologic classification. Some were shaped into strangely bulbous forms, and others flat expanses of microbial mats. Some were above water, and others under it. They are understood to be among the earliest living organisms on Earth, and also just so happened to oxygenate our atmosphere, setting the stage for all life to come. It took 900 million years.

    5
    Stromatolites: Straddling the biologic and the geologic, stromatolites are bound cyanobacteria; organisms tied to the oxygenation of the planet that began 3.5 billion years ago, setting the stage for the rest of life on Earth to come.

    In some respects, what I was doing was not far from science. I was exploring and recording the world, and relying on the help of scientists and their tools and data. But my goals were also not solely—or even primarily—scientific. The Oldest Living Things is an eccentric archive and time capsule, constructed across disciplines, and at its heart a conceptual art project.

    I also financed it on my own. While curiosity and experimentation define the work of both artists and scientists, the money comes from different places. I have yet to encounter a wholly independent scientist, conducting research without institutional funding, whereas there are very few fully—or even partially—supported artists. As for me, I couldn’t not do the work, despite the fact that it came at great personal expense. I racked up credit card debt and student loans from an ill-fated foray into a Ph.D. program, bartered artwork for foreign travel immunizations and dentistry, accepted help from family, and borrowed money from friends.

    One of my primary goals with this work was to create a little jolt of recognition at the shallowness of human timekeeping and the blink that is a human lifespan. Does our understanding of time have to be tethered to our physiological experience of it? I don’t think so. Deep time is like deep water: We are constantly brought back to the surface, pulled by the wants and needs of the moment. But like exercising any sort of muscle, the more we access deep time, the more easily accessible it becomes, and the more likely we are to engage in long-term thinking. The more we embrace long-term thinking, the more ethical our decision-making becomes. It is not the job of traditional science to interpret and translate its findings. Art, on the other hand, is a great mediator.

    The dialogue with environmental conservation is a perfect example of the importance of blending art, science, and long-term thinking. Our eyes might glaze over at reading about CO2 levels at 400+ parts per million, as vital as that statistic is, because it is so hard to relate to such an abstraction. But take, for example, the 9,550-year-old spruce tree on a high mountain plateau in Sweden. For the first 9,500 years of its life it lived as a shrubby mass of branches, close to the ground. But around 50 years ago, a tall and spindly center trunk shot up: a direct effect of a warming climate. It is, in essence, a portrait of climate change. Perhaps by visualizing such impacts, by anthropomorphizing these ancient lives and activating the science that tells their stories through an artistic lens, we might engage more readily in the long-term thinking required to extend their lives, and by proxy, our own.

    Engagement with the sciences is part of how I measure the impact of the Oldest Living Things as well. Recently, a scientist that I’ve never met sent me an email saying that after reading my book, he is now approaching his work with a different, more open mindset. To me, that indicates something has been set into motion. After all, meaning is not made of lone facts, lone people, or lone disciplines, nor is it found in the valuing of the objective over the subjective. Rather, meaning comes by way of knitting together a bigger picture, filled with color and texture, and meant to be felt and understood. We most fully understand what we can internalize—that which becomes part of us. The importance of specializing can’t be discarded, but working only within one discipline and strictly adhering to its rules is likely only to generate one kind of work, one kind of result.

    We very well might end up missing the forest for the trees.

    6
    Chestnut of 100 Horses: The approximately 3,000-year-old Castagno dei Cento Cavalli in Sicily lives within the range of Mount Etna, seen here after a shower of lava.

    See the full article here.

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    Welcome to Nautilus. We are delighted you joined us. We are here to tell you about science and its endless connections to our lives. Each month we choose a single topic. And each Thursday we publish a new chapter on that topic online. Each issue combines the sciences, culture and philosophy into a single story told by the world’s leading thinkers and writers. We follow the story wherever it leads us. Read our essays, investigative reports, and blogs. Fiction, too. Take in our games, videos, and graphic stories. Stop in for a minute, or an hour. Nautilus lets science spill over its usual borders. We are science, connected.

     
  • richardmitnick 10:42 am on March 24, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , NC State University   

    From NC State: “Shrinking Habitats Have Adverse Effects on World Ecosystems” 

    NC State bloc

    North Carolina State University

    1
    A new study shows habitat fragmentation has harmful effects to world ecosystems. Researchers studied fragmentation at seven sites across five continents. Photo courtesy of Nick Haddad, NC State University

    An extensive study of global habitat fragmentation – the division of habitats into smaller and more isolated patches – points to major trouble for a number of the world’s ecosystems and the plants and animals living in them.

    The study shows that 70 percent of existing forest lands are within a half-mile of the forest edge, where encroaching urban, suburban or agricultural influences can cause any number of harmful effects – like the losses of plants and animals.

    The study also tracks seven major experiments on five continents that examine habitat fragmentation and finds that fragmented habitats reduce the diversity of plants and animals by 13 to 75 percent, with the largest negative effects found in the smallest and most isolated fragments of habitat.

    The study, led by a researcher from North Carolina State University and involving about two dozen researchers across the globe, is reported today in a paper published in Science Advances.

    The researchers assembled a map of global forest cover and found very few forest lands unencumbered by some type of human development.

    “It’s no secret that the world’s forests are shrinking, so this study asked about the effects of this habitat loss and fragmentation on the remaining forests,” said Dr. Nick Haddad, William Neal Reynolds Distinguished Professor of Biological Sciences at NC State and the corresponding author of the paper.

    “The results were astounding. Nearly 20 percent of the world’s remaining forest is the distance of a football field – or about 100 meters – away from a forest edge. Seventy percent of forest lands are within a half-mile of a forest edge. That means almost no forest can really be considered wilderness.”

    The study also examined seven existing major experiments on fragmented habitats currently being conducted across the globe; some of these experiments are more than 30 years old.

    Covering many different types of ecosystems, from forests to savannas to grasslands, the experiments combined to show a disheartening trend: Fragmentation causes losses of plants and animals, changes how ecosystems function, reduces the amounts of nutrients retained and the amount of carbon sequestered, and has other deleterious effects.

    “The initial negative effects were unsurprising,” Haddad said. “But I was blown away by the fact that these negative effects became even more negative with time. Some results showed a 50 percent or higher decline in plant and animals species over an average of just 20 years, for example. And the trajectory is still spiraling downward.”

    Haddad points to some possible ways of mitigating the negative effects of fragmentation: conserving and maintaining larger areas of habitat; utilizing landscape corridors, or connected fragments that have shown to be effective in achieving higher biodiversity and better ecosystem function; increasing agricultural efficiency; and focusing on urban design efficiencies.

    “The key results are shocking and sad,” Haddad said. “Ultimately, habitat fragmentation has harmful effects that will also hurt people. This study is a wake-up call to how much we’re affecting ecosystems – including areas we think we’re conserving.”

    The study was supported by the National Science Foundation.

    See the full article here.

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    NC State Campus

    As a land-grant institution, NC State itself was born as an idea: that higher education should bring economic, societal and intellectual prosperity to the masses. From our origins teaching the agricultural and mechanical arts, we’ve grown to become a pre-eminent research enterprise that advances knowledge in science, technology, engineering, math, design, the humanities and social sciences, textiles and veterinary medicine.

     
  • richardmitnick 6:24 pm on March 23, 2015 Permalink | Reply
    Tags: Applied Research & Technology, high-intensity focused ultrasound therapy,   

    From New Scientist: “Ultrasound killed the surgical star” 2014 But Valuable 

    NewScientist

    New Scientist

    06 January 2014
    Helen Thomson

    1
    From brain to prostate, focused waves of sound can reach places a scalpel can’t, putting us on the brink of a surgical shake-up.
    (Image: Patrick George)

    PHYLLIS is having brain surgery. But she is wide awake. There are no scalpels and no blood, sliced flesh or bone in sight. Instead, the surgeon carefully places a cap on top of Phyllis’s head and flicks a switch. Deep inside her brain, a tiny region of tissue heats up and begins to burn, while surrounding brain cells are left unscathed. Later that day, Phyllis is able to go home, free from the neurological disorder that for the past 30 years has made her right hand tremble violently whenever she tried to use it.

    She has a form of ultrasound to thank for her remarkable recovery. Just as the sun’s rays can be focused by a magnifying glass to burn a piece of paper, high-intensity ultrasound waves can be concentrated to burn human tissue. The waves are harmless until they converge at the focal point, so a surgeon can operate deep inside the body without harming the surrounding tissue.

    This high-intensity focused ultrasound (HIFU) requires no cuts to be made, and many operations don’t even need an anaesthetic, so the patient can be in and out of hospital within a day. “When you’re dealing with a lot of very sick people, that’s a huge advantage,” says Gail ter Haar, who studies ultrasound at the Institute of Cancer Research in London.

    After promising trials treating prostate cancer, it is now looking as if HIFU could become a medical Swiss army knife for all kinds of procedures. And even in parts of the body where the focused waves can’t burn away tissue directly, they can still boost the uptake of drugs in specific organs. The method has even been used to prevent severe illness in fetuses in the womb.

    Phyllis’s success story is the latest step of a journey that began 70 years ago. John Lynn and his colleagues at Columbia University in New York were the first to try targeting ultrasound waves to destroy biological tissue, in the 1940s. Although they managed to create lesions in cat brains with minimal disruption to non-targeted areas, the need for a craniotomy – in which a bone flap is removed from the skull – together with a lack of sophisticated imaging technologies, meant there was limited interest in the technology for general surgery. Now, with more advanced transmitters that can focus beams behind hard tissue like bone, and imaging technology such as MRI, doctors can operate more accurately, targeting areas of tissue sometimes just fractions of a millimetre across.

    That precision looks set to revolutionise the treatment of prostate cancer. Conventionally, when tumours need to be eliminated, the entire prostate is removed, which can damage nerves and the muscles that control the ability to relieve yourself on demand. The result is that 70 per cent of patients lose the ability to get erections, and about 15 per cent become incontinent. A less-invasive option is radiotherapy, but it can still cause some damage to surrounding nerves. What’s more, radiotherapy is unlikely to be repeated if the cancer returns, because the risk becomes too great that DNA damage from the radiation will cause secondary tumours.

    With focused ultrasound, however, surgeons can burn away tumours bit by bit, targetting areas the size of a grain of rice (see “No blood, sweat or tears”). Trial results so far have been impressive: in a 2012 study of about 40 men receiving HIFU, 90 per cent could maintain an erection by the end of the study, and no man was left incontinent. One year later, 95 per cent showed no signs of the disease (Lancet Oncology, vol 13, p 622).

    The recovery times are particularly notable. “We’ve had some people who’ve said they’ve been shopping the same day as the procedure,” says Louise Dickinson at University College London, who is investigating the long-term outcomes of using the therapy for prostate cancer. “One man said it was easier than going to the dentist for a filling.” Widespread clinical trials of ultrasound treatment for prostate cancer are now under way, but further evidence of its long-term effectiveness will be needed before it is a recommended treatment.

    Buoyed by the promising results for prostate cancer, a range of trials are now investigating using sound to treat other disorders, including pancreatic cancer and lumps that form in the thyroid gland that can lead to cancer. One of the more ambitious ideas is to use HIFU to tackle problems deep in the brain. The technique has huge advantages, not least because you avoid cracking into the skull. What’s more, you can bypass the healthy layers of brain, preserving normal functions.

    That’s not to say it is simple. The rate at which ultrasound passes through different tissue types varies – bone absorbs a lot of sound, whereas the jelly-like tissue of the brain takes in much less. To make matters worse, our skulls are not a uniform thickness all the way around. So surgeons have to use CAT scans to measure the bone density at thousands of points around the scalp. Later, a cap full of ultrasound emitters, called transducers, will be placed on the patient’s head. Each transducer is tuned using information about the bone density underneath so that it emits just the right frequency, for just the right amount of time, to focus the waves at the desired point in the brain.

    Last year, the technique was used to treat 15 people with essential tremor, Phyllis among them (New England Journal of Medicine, vol 369, p 640). To do so, the doctors singed a tiny area of the thalamus that relays motor signals to the cortex – thus blocking some of the abnormal neuronal activity that would otherwise be transmitted to the muscles and cause shaking. “The whole procedure probably took less than 2 hours, and apart from a strange buzzing sensation, it was completely painless,” says Phyllis. Because the trial was designed to test the safety of the procedure, they only aimed to treat the movements in her right hand. The results were immediate. “As soon as I came out of hospital, my handwriting was perfect, like it used to be,” she says. “It’s got a little worse over time but it’s so much better than my left hand.” The other 14 patients in the trial experienced similar improvements, and although side effects included temporary problems with speech, and for four patients, minor but persistent alterations to sensations in their face or fingers, all agreed that it significantly improved their quality of life.

    The hope is that we might be on the cusp of a new wave of non-invasive brain surgery. “Soon, we’ll be starting a trial that will attempt to reduce movement problems in Parkinson’s and treat brain tumours,” says Neal Kassell, director of the Focused Ultrasound Foundation in Charlottesville, Virginia.

    Despite these successes, HIFU has its limitations. Bone cancer, for instance, is almost untouchable, because skeletal tissue quickly absorbs the ultrasound waves. “It’s hard to get any energy deep into the bone,” says Wladyslaw Gedroyc, a consultant radiologist at St Mary’s Hospital in London. Conventional surgery, too, struggles to remove this kind of cancer, because it is difficult to bypass vital nerves, and any bone that is removed has to be reconstructed with a graft or prosthesis.
    Bursting bubbles

    Focused ultrasound may be much more than a replacement for the scalpel, however. It could open doors to procedures that would be impossible by conventional methods. Of particular interest is using ultrasound to direct the delivery of drugs. One approach would be to create medicines that are injected in an inert form, and then activated near to a tumour using heat from HIFU. The idea is to boost the dose where it is most needed while reducing side effects in the rest of the body.

    In other instances, the treatment could be aided by “microbubbles”. This phenomenon was discovered by accident, or so the legend goes, says Eleanor Stride at the University of Oxford. “They used to be made just by shaking blood about and putting it back in.” Now, you can buy ready-made microbubbles that are between 1 and 10 micrometres across. They are comprised of a bubble filled with gas, supported by an outer shell made of lipids, proteins or polymers. The bubbles are often used during ultrasound scans, since they increase the contrast of the blood supply compared with the surrounding tissue. Once they are placed in the path of an ultrasound wave of the right frequency and intensity, however, they expand and contract until they suddenly collapse, creating a shockwave.

    Do this in the brain, and you could perforate the blood-brain barrier – the layer of membranes around capillaries that separate the blood from the extracellular fluid that flows around the brain. This barrier makes it difficult to deliver drugs into the brain during chemotherapy, for instance – but puncturing it is a tricky procedure, because permanent damage would weaken the brain’s defences against bacteria. A 2012 study in macaques, however, identified the specific frequency necessary to induce a reversible disruption to this barrier for just a few hours – enough time to allow drugs to be delivered to the brain with a minimal risk of infection (PLoS One, doi.org/p9n).

    Elsewhere in the body, it might be possible to place traditional chemotherapy agents into microbubbles and direct their implosion at the site you want destroyed. “It’s not been done yet, but we’re getting very close,” says Stride. Her colleague Constantin Coussios is about to take the first step. This year, his team will inject a chemotherapy drug into people with liver cancer. The drug will be encased in a lipid wrapper that can be broken down using ultrasound. If that works, they will then try to use microbubbles, filled with gas and the drug, as a vehicle – with the added advantage that the shockwave of the imploding bubbles would drive its chemical load deeper into the tumour, where it can do more damage. A similar approach would be particularly useful to push drugs into the bone cancers that are so difficult to reach with traditional surgery.

    Focused sound can even help doctors to treat patients at times when they were thought to be untouchable – such as when they are still in the womb. This was demonstrated for the first time in 2013, with a condition known as “twin reversed arterial perfusion”. This rare disorder involves two fetuses – one of which develops normally, while the other fails to develop a head, arms or heart. The two fetuses are connected by an umbilical cord that passes through the placenta, and the twin without a heart relies on blood pumped from its twin to stay alive. As a result, the healthy twin has to work extra hard to sustain both, which often results in heart failure and death.

    Surgeons used HIFU, between 13 and 17 weeks after conception, to sever the abnormal fetus from the placenta and release the healthy twin of this burden. The baby boy was later delivered successfully (Ultrasound in Obstetrics & Gynecology, vol 42, p 112).

    The success of such a delicate procedure offers a glimpse of what the future might hold. Kassell, for one, is sure that we are only just beginning to understand the potential of this technology. “It’s a stick that we’re still working out how to wield,” he says.

    Gedroyc agrees. “You have here a very powerful tool,” he says. “Once you start thinking about it, you’re really only limited by how imaginative you are.”

    This article appeared in print under the headline “Surgery’s new sound”

    See the full article here.

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  • richardmitnick 12:43 pm on March 23, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , Ohio State University   

    From OSU: “Landmark study proves that magnets can control heat and sound” 

    OSU

    Ohio State University

    March 23, 2015
    Pam Frost Gorder

    1
    Researchers at The Ohio State University have discovered how to control heat with a magnetic field. An experiment proved that the phonon—the elementary particle that carries heat and sound—has magnetic properties. Here Joseph Heremans, Ohio Eminent Scholar in Nanotechnology, holds an artist’s rendering of a phonon heating solid material. Artist’s rendering by Renee Ripley. Photo by Kevin Fitzsimons, courtesy of The Ohio State University

    Researchers at The Ohio State University have discovered how to control heat with a magnetic field.

    In the March 23 issue of the journal Nature Materials, they describe how a magnetic field roughly the size of a medical MRI reduced the amount of heat flowing through a semiconductor by 12 percent.

    The study is the first ever to prove that acoustic phonons—the elemental particles that transmit both heat and sound—have magnetic properties.

    “This adds a new dimension to our understanding of acoustic waves,” said Joseph Heremans, Ohio Eminent Scholar in Nanotechnology and professor of mechanical engineering at Ohio State. “We’ve shown that we can steer heat magnetically. With a strong enough magnetic field, we should be able to steer sound waves, too.”

    1
    Joseph Heremans

    People might be surprised enough to learn that heat and sound have anything to do with each other, much less that either can be controlled by magnets, Heremans acknowledged. But both are expressions of the same form of energy, quantum mechanically speaking. So any force that controls one should control the other.

    “Essentially, heat is the vibration of atoms,” he explained. “Heat is conducted through materials by vibrations. The hotter a material is, the faster the atoms vibrate.

    “Sound is the vibration of atoms, too,” he continued. “It’s through vibrations that I talk to you, because my vocal chords compress the air and create vibrations that travel to you, and you pick them up in your ears as sound.”

    The name “phonon” sounds a lot like “photon.” That’s because researchers consider them to be cousins: Photons are particles of light, and phonons are particles of heat and sound. But researchers have studied photons intensely for a hundred years—ever since Einstein discovered the photoelectric effect. Phonons haven’t received as much attention, and so not as much is known about them beyond their properties of heat and sound.

    2
    Hyungyu Jin

    This study shows that phonons have magnetic properties, too.

    “We believe that these general properties are present in any solid,” said Hyungyu Jin, Ohio State postdoctoral researcher and lead author of the study.

    The implication: In materials such as glass, stone, plastic—materials that are not conventionally magnetic—heat can be controlled magnetically, if you have a powerful enough magnet. The effect would go unnoticed in metals, which transmit so much heat via electrons that any heat carried by phonons is negligible by comparison.

    There won’t be any practical applications of this discovery any time soon: 7-tesla magnets like the one used in the study don’t exist outside of hospitals and laboratories, and the semiconductor had to be chilled to -450 degrees Fahrenheit (-268 degrees Celsius)—very close to absolute zero—to make the atoms in the material slow down enough for the phonons’ movements to be detectible.

    That’s why the experiment was so difficult, Jin said. Taking a thermal measurement at such a low temperature was tricky. His solution was to take a piece of the semiconductor indium antimonide and shape it into a lopsided tuning fork. One arm of the fork was 4 mm wide and the other 1 mm wide. He planted heaters at the base of the arms.

    The design worked because of a quirk in the behavior of the semiconductor at low temperatures. Normally, a material’s ability to transfer heat would depend solely on the kind of atoms of which it is made. But at very low temperatures, such as the ones used in this experiment, another factor comes into play: the size of the sample being tested. Under those conditions, a larger sample can transfer heat faster than a smaller sample of the same material. That means that the larger arm of the tuning fork could transfer more heat than the smaller arm.

    Heremans explained why.

    “Imagine that the tuning fork is a track, and the phonons flowing up from the base are runners on the track. The runners who take the narrow side of the fork barely have enough room to squeeze through, and they keep bumping into the walls of the track, which slows them down. The runners who take the wider track can run faster, because they have lots of room.

    “All of them end up passing through the material—the question is how fast,” he continued. “The more collisions they undergo, the slower they go.”

    In the experiment, Jin measured the temperature change in both arms of the tuning fork and subtracted one from the other, both with and without a 7-tesla magnetic field turned on.

    In the absence of the magnetic field, the larger arm on the tuning fork transferred more heat than the smaller arm, just as the researchers expected. But in the presence of the magnetic field, heat flow through the larger arm slowed down by 12 percent.

    So what changed? Heremans said that the magnetic field caused some of the phonons passing through the material to vibrate out of sync so that they bumped into one another, an effect identified and quantified through computer simulations performed by Nikolas Antolin, Oscar Restrepo and Wolfgang Windl, all of Ohio State’s Department of Materials Science and Engineering.

    In the larger arm, the freedom of movement worked against the phonons—they experienced more collisions. More phonons were knocked off course, and fewer—12 percent fewer—passed through the material unscathed.

    The phonons reacted to the magnetic field, so the particles must be sensitive to magnetism, the researchers concluded. Next, they plan to test whether they can deflect sound waves sideways with magnetic fields.

    Co-authors on the study included Stephen Boona, a postdoctoral researcher in mechanical and aerospace engineering; and Roberto Myers, an associate professor of materials science and engineering, electrical and computer engineering and physics.

    Funding for the study came from the U.S. Army Research Office, the U.S. Air Force Office of Scientific Research and the National Science Foundation (NSF), including funds from the NSF Materials Research Science and Engineering Center at Ohio State. Computing resources were provided by the Ohio Supercomputer Center.

    See the full article here.

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  • richardmitnick 10:27 am on March 22, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , ,   

    From Science 2.0: “Early Kidney Cancer Detection With Urine Test” 

    Science 2.0 bloc

    Science 2.0

    March 22nd 2015
    News Staff

    80 percent of patients survive when kidney cancer is detected early – but it is often not easy. However, finding it early has been among the disease’s greatest challenges.

    Kidney cancer is the seventh most common cancer in men and the 10th most common in women, affecting about 65,000 people each year in the United States. About 14,000 patients die of the disease annually. Like most cancers, kidney tumors are easier to treat when diagnosed early. But symptoms of the disease, such as blood in the urine and abdominal pain, often don’t develop until later, making early diagnosis difficult.

    Now, researchers have developed a noninvasive method to screen for kidney cancer that involves measuring the presence of proteins in the urine. They found that the protein biomarkers were more than 95 percent accurate in identifying early-stage kidney cancers. In addition, there were no false positives caused by non-cancerous kidney disease.

    1
    Evan D. Kharasch, M.D., Ph.D., (left) and Jeremiah J. Morrissey, Ph.D. Credit: Elizabethe Holland Durando

    “These biomarkers are very sensitive and specific to kidney cancer,” said senior author Evan D. Kharasch, MD, PhD, of Washington University School of Medicine in St. Louis. “The most common way that we find kidney cancer is as an incidental, fortuitous finding when someone has a CT or MRI scan. It’s not affordable to use such scans as a screening method, so our goal has been to develop a urine test to identify kidney cancer early.”

    When kidney cancer isn’t discovered until after it has spread, more than 80 percent of patients die within five years.

    With researchers from the Siteman Cancer Center, the Mallinckrodt Institute of Radiology and the Division of Urologic Surgery, Kharasch and principal investigator Jeremiah J. Morrissey, PhD, professor of anesthesiology, analyzed urine samples from 720 patients at Barnes-Jewish Hospital who were about to undergo abdominal CT scans for reasons unrelated to a suspicion of kidney cancer. Results of the scans let the investigators determine whether or not patients had kidney cancer. As a comparison, they also analyzed samples from 80 healthy people and 19 patients previously diagnosed with kidney cancer.

    The researchers measured levels of two proteins in the urine — aquaporin-1 (AQP1) and perlipin-2 (PLIN2). None of the healthy people had elevated levels of either protein, but patients with kidney cancer had elevated levels of both proteins.

    In addition, three of the 720 patients who had abdominal CT scans also had elevated levels of both proteins. Two of those patients were diagnosed subsequently with kidney cancer, and the third patient died from other causes before a diagnosis could be made.

    “Each protein, or biomarker, individually pointed to patients who were likely to have kidney cancer, but the two together were more sensitive and specific than either by itself,” said Morrissey. “When we put the two biomarkers together, we correctly identified the patients with kidney cancer and did not have any false positives.”

    Even when patients had other types of non-cancerous kidney disease, levels of the two proteins in the urine were not elevated and did not suggest the presence of cancer.

    “Patients with other kinds of cancer or other kidney diseases don’t have elevations in these biomarkers,” Kharasch said. “So in addition to being able to detect kidney cancer early, another advantage of using these biomarkers may be to show who doesn’t have the disease.”

    Not all kidney masses found by CT scans turn out to be cancerous, he said. In fact, about 15 percent are not malignant.

    “But a CT scan can only tell you whether there is a mass in the kidney, not whether it’s cancer,” Kharasch said. “Currently, the only way to know for sure is to have surgery, and unfortunately, 10 to 15 percent of kidneys removed surgically turn out to be normal.”

    Kharasch and Morrissey are working to develop an easy-to-use screening test for kidney cancer, much like mammograms, colonoscopies or other tests designed to identify cancer at early, more treatable stages before patients have symptoms.

    “By and large, patients don’t know they have kidney cancer until they get symptoms, such a blood in the urine, a lump or pain in the side or the abdomen, swelling in the ankles or extreme fatigue,” Morrissey said. “And by then, it’s often too late for a cure. Metastatic kidney cancer is extremely difficult to treat, and if the disease is discovered after patients have developed symptoms, they almost always have metastases. So we’re hoping to use the findings to quickly get a test developed that will identify patients at a time when their cancer can be more easily treated.”

    Funded by the Barnes-Jewish Hospital Frontier Fund and The Department of Anesthesiology at Washington University School of Medicine in St. Louis, with additional support from the Bear Cub Fund of Washington University, Barnes-Jewish Hospital Foundation and Washington University Institute of Clinical and Translational Science, with additional funding from the National Cancer Institute (NCI) of the National Institutes of Health (NIH). NIH grant numbers R01CA141521 and UL1 TR000448.

    Morrissey JJ, Mellnick VM, Luo J, Siegel MJ, Figenshau RS, Bhayani S, Kharasch ED. Evaluation of urine aquaporin 1 and perilipin 2 concentrations as biomarkers to screen for renal cell carcinoma. JAMA Oncology, published online March 19, 2015.

    See the full article here.

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  • richardmitnick 7:54 am on March 22, 2015 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From MedicalXpress: “Vitamin D may keep low-grade prostate cancer from becoming aggressive” 

    Medicalxpress bloc

    MedicalXpress

    Taking vitamin D supplements could slow or even reverse the progression of less aggressive, or low-grade, prostate tumors without the need for surgery or radiation, a scientist will report today.

    1

    His team will describe the approach in one of nearly 11,000 presentations at the 249th National Meeting & Exposition of the American Chemical Society (ACS).

    If a tumor is present in a prostate biopsy, a pathologist grades its aggressiveness on a scale known as the Gleason grading system.

    2
    Gleason grade Lower grades are associated with small, closely packed glands. Cells spread out and lose glandular architecture as grade increases.

    Tumors with Gleason scores of 7 and above are considered aggressive and likely to spread, requiring surgical removal of the prostate gland (prostatectomy) or radiation therapy. In contrast, prostate tumors with Gleason scores of 6 and below are less aggressive, and in some cases may cause no symptoms or health problems for the duration of the man’s life.

    In cases of low-grade prostate cancer, many urologists do not treat the disease, but instead do what’s called “active surveillance,” says Bruce Hollis, Ph.D., who is at the Medical University of South Carolina. “The cure—meaning surgery or radiation—is probably worse than the disease, so they wait a year and then do another biopsy to see where the patient stands.”

    However, knowing that they have even low-grade prostate cancer can cause patients and their families excessive anxiety, which prompts some of the men to undergo an elective prostatectomy, despite the risk of complications such as infection, urinary incontinence and erectile dysfunction. But a man must wait 60 days from the time of his biopsy before he can undergo a prostatectomy, so that inflammation from the biopsy can subside.

    Hollis wondered if giving these men vitamin D supplements during the 60-day waiting period would affect their prostate cancer. His previous research had shown that when men with low-grade prostate cancer took vitamin D supplements for a year, 55 percent of them showed decreased Gleason scores or even complete disappearance of their tumors compared to their biopsies a year before (J. Clin. Endocrinol. Metab., 2012, DOI: 10.1210/jc.2012-1451).

    In a new randomized, controlled clinical trial, his team assigned 37 men undergoing elective prostatectomies either to a group that received 4,000 U of vitamin D per day, or to a placebo group that didn’t receive vitamin D. The men’s prostate glands were removed and examined 60 days later.

    Preliminary results from this study indicate that many of the men who received vitamin D showed improvements in their prostate tumors, whereas the tumors in the placebo group either stayed the same or got worse. Also, vitamin D caused dramatic changes in the expression levels of many cell lipids and proteins, particularly those involved in inflammation. “Cancer is associated with inflammation, especially in the prostate gland,” says Hollis. “Vitamin D is really fighting this inflammation within the gland.”

    The protein most strongly induced by vitamin D was one called growth differentiation factor 15 (GDF15). Previous studies by other groups showed that GDF15 dials down inflammation, and many aggressive prostate cancers make little or no GDF15.

    The new research suggests that vitamin D supplementation may improve low-grade prostate cancers by reducing inflammation, perhaps lessening the need for eventual surgery or radiation treatment. “We don’t know yet whether vitamin D treats or prevents prostate cancer,” says Hollis. “At the minimum, what it may do is keep lower-grade prostate cancers from going ballistic.”

    Hollis notes that the dosage of vitamin D administered in the study—4,000 U—is well below the 10,000-20,000 U that the human body can make from daily sun exposure. “We’re treating these guys with normal body levels of vitamin D,” he says. “We haven’t even moved into the pharmacological levels yet.”

    See the full article here.

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    Medical Xpress is a web-based medical and health news service that is part of the renowned Science X network. Medical Xpress features the most comprehensive coverage in medical research and health news in the fields of neuroscience, cardiology, cancer, HIV/AIDS, psychology, psychiatry, dentistry, genetics, diseases and conditions, medications and more.

     
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