Tagged: Biology Toggle Comment Threads | Keyboard Shortcuts

  • richardmitnick 1:37 pm on October 31, 2014 Permalink | Reply
    Tags: , Biology, ,   

    From NOVA: “Bioinspired Underwater Glue Could Soon Replace Stitches” 

    PBS NOVA

    NOVA

    Fri, 31 Oct 2014
    Sarah Schwartz

    It’s a sticky situation—in the best possible way. By combining proteins that mussels and bacteria use to stick to surfaces, scientists at the Massachusetts Institute of Technology have created a strong new underwater glue. This adhesive could tackle an important challenge in various fields, including surgery, where repairing wet surfaces is essential.

    For years, scientists have used marine organisms for insight in producing underwater glues. Water forms a “weak boundary” on surfaces it contacts, which prevents adhesives from attaching, says Dr. Herbert Waite, Professor of Molecular, Cellular, and Developmental Biology at the University of California, Santa Barbara. This becomes a challenge in fields where wet surfaces need to be repaired—marine salvage, dentistry, surgery, and more. But organisms like mussels and barnacles regularly overcome this obstacle, binding easily to wet rocks.

    The MIT team turned to these organisms for inspiration—and ingredients. “One of the promises in synthetic biology is to be able to mix and match and optimize biologically based materials,” says Dr. Timothy Lu, an associate professor in MIT’s Synthetic Biology group and an author of the study. Lu and his colleagues combined proteins from two different sources—the feet of mussels, and E. coli bacteria.

    mus
    By combining proteins that mussels and bacteria use to stick to surfaces, scientists at MIT have created a strong new underwater glue.

    A good adhesive has two properties, Waite says: It has to be able to stick to other surfaces, and it also has to bind to itself. DOPA, the protein mussels use to adhere to surfaces, can do both, but its behavior depends upon the conditions of its environment. Mussels use various “tricks” to control their DOPA that aren’t fully understood, Waite says. If you’re not a mussel, it can be hard to manage DOPA’s behavior.

    That’s where the second protein helps. Amyloids are also adhesive, water-resistant, and link strongly to one another. Barnacles, algae, and bacteria use them to stick to surfaces. Lu and his team saw an opportunity: “[W]e thought by combining the bacteria with the mussels, we might be able to get some synergistic behavior,” says Lu.

    The result was a glue stronger than any other bio-derived or bio-inspired adhesive made to date. Waite, who was not involved with the study, says the results “really impressed” him. The researchers only asked DOPA to work in the form where it adheres to surfaces, he explains, while the amyloid proteins held the glue together. This joint behavior gives the glue its strength.

    Lu believes that this is only the beginning. “We only looked at two of the proteins that are involved in mussel adhesion…If we could combine multiple proteins on top of that, maybe we can even get stronger performance,” he says. While the group has been focused on adhesion alone, in the future, the group plans to explore potential underwater and biomedical uses, says Lu.

    These biomedical applications could be profound, especially in surgery. Waterproof glues could help seal internal wounds, even when drenched in blood and other fluids. Sutures or staples are currently used to close such holes, but these are hard to affix and can damage tissues, says Dr. Jeffrey Karp, an associate professor at Brigham and Women’s Hospital and Harvard Medical School. Karp, who was not involved in the MIT study.

    “There’s a huge unmet need for better adhesives,” says Karp, who is also a co-founder of Gecko Biomedical, which is developing medical adhesives. “There’s really nothing available in the clinic that works well and doesn’t have its drawbacks,” he adds, calling Lu’s team’s work “excellent and very promising.” The next step, Karp says, is to test the glue at larger scales.

    To work inside the human body, an adhesive must be biocompatible, or “cell-friendly.” But strong glues are often toxic. “We really don’t have anything that is strong and biocompatible,” says Dr. Pedro del Nido, a specialist in cardiac surgery at Boston’s Children’s Hospital who was not involved with the MIT study.

    Lu says his group is interested in testing for biocompatibility and believes that natural sources will yield better biocompatible materials. Looking to nature for advice has served him well so far. “[N]ature has solved a lot of the same problems that we deal with in pretty creative ways…Often times, borrowing upon nature and then applying the tools that we have in our arsenal to improve those properties, I think, is a really powerful way to go.”

    See the full article here.

    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.

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 6:18 pm on October 29, 2014 Permalink | Reply
    Tags: , Biology,   

    From PNNL: “New Assay Platform Detects Largest Number of Known Biotoxins Simultaneously” 


    PNNL Lab

    October 2014
    No Writer Credit

    New Assay Platform Detects Largest Number of Known Biotoxins Simultaneously

    Rapid, inexpensive microarray increases ability to identify, treat toxin exposure

    Results: The largest panel of biotoxins to be simultaneously detected to date has been achieved using an assay platform developed by scientists at Pacific Northwest National Laboratory. The enzyme-linked immunosorbent assay (ELISA) microarray simultaneously detected 10 plant and microbial toxins in buffer and clinical and environmental samples. These included ricin, botulinum neurotoxins (BoNT), shiga (STX), and staphylococcal enterotoxin B (SEB). Previously, the largest number of toxins to be simultaneously detected has been six.

    ricin
    A molecule of ricin, one of the most deadly and common toxins discovered to date. An assay developed at Pacific Northwest National Laboratory can detect ricin and nine other biotoxins simultaneously, the largest panel to date.

    “Most assays to detect toxins target one or two toxins at a time, at best. In the event of a bioterrorist attack, it may not be obvious which agent was released, although this knowledge is critical for delivering appropriate medical treatment,” said Dr. Susan Varnum, a biologist at PNNL who led the study, which appears in Analyst.

    “There’s a pressing need for assays that analyze multiple toxins simultaneously so that in case of exposure, differentiation of multiple biothreat toxins can occur early enough for appropriate care to be given,” Varnum added.

    ELISAs are widely used to detect the presence of a single antigen-or biomarker-in biological samples. This new microarray ELISA platform allows the highly sensitive detection of up to 50 antigens simultaneously. Typically, commercially available antibodies are used in the development of these assays. However, to differentiate among six closely related BoNT serotypes, the scientists used high-affinity reagents generated in the laboratory of Dr. James Marks, University of California, San Francisco School of Medicine. The new, highly sensitive assay design developed by PNNL is rapid, specific, and simple enough for easy adoption by other research groups.

    Why It Matters: Protein toxins are considered to be potential biological threat agents because of their extreme toxicity, widespread availability, and ease of use. Biothreat toxins have been stockpiled for bioweapon use and even used in previous bioterrorism events. To treat exposure to these toxins, sensitive and specific detection systems that can quickly identify multiple biothreat toxins are needed. The new assay platform affords simultaneous detection of 10 biothreat toxins simultaneously in a diverse range of clinical and environmental samples, including blood, saliva, urine, stool, milk, and apple juice.

    Methods: The research team based their diagnostic assay on the antibody microarray approach. Antibody protein microarrays are miniaturized, solid-phase analytical assays for the detection of many proteins in parallel. This approach uses an array of high-affinity capture reagents, or antibodies, immobilized on a glass slide. These spatially arrayed antibodies bind a specific antigen from a sample added to the array. A second, labeled antibody that recognizes the same antigen as the first antibody then is used for detection to form a “sandwich” assay. This sandwich approach favors specificity in analyte detection.

    venn
    A Venn diagram outlining and contrasting some aspects of the fields of bio-MEMS, lab-on-a-chip, μTAS.

    The assay not only sensitively detected the biotoxins in buffer but also in complex clinical and environmental matrices at levels in the low picogram per mL-1 range and with a minimal sample volume of 20 microliters. The multiplex ELISA-based protein antibody microarray developed at PNNL demonstrates an excellent assay that can achieve some of the lowest detection limits and maintain sensitivity below the reported median lethal dose (LD50) in a wide range of biological fluids.

    Acknowledgments

    Sponsors: This research was supported by the National Institute of Allergy and Infectious Diseases.

    Research Team: Kathryn Jenko, Yanfang Zhang, Yulia Kostenko, and Susan Varnum (PNNL); Yongfeng Fan, Consuelo Garcia-Rodriguez, Jianlong Lou, and James Marks (UCSF).

    Research Area: Biological Systems Science

    Reference: Jenko K, Y Zhang, Y Kostenko, Y Fan, C Garcia-Rodriguez, J Lou, JD Marks, and SM Varnum. 2014. Development of an ELISA Microarray Assay for the Sensitive and Simultaneous Detection of Ten Biodefense Toxins. Analyst 139(20):5093-5102. DOI: 10.1039/c4an01270d.

    See the full article here.

    Pacific Northwest National Laboratory (PNNL) is one of the United States Department of Energy National Laboratories, managed by the Department of Energy’s Office of Science. The main campus of the laboratory is in Richland, Washington.

    PNNL scientists conduct basic and applied research and development to strengthen U.S. scientific foundations for fundamental research and innovation; prevent and counter acts of terrorism through applied research in information analysis, cyber security, and the nonproliferation of weapons of mass destruction; increase the U.S. energy capacity and reduce dependence on imported oil; and reduce the effects of human activity on the environment. PNNL has been operated by Battelle Memorial Institute since 1965.

    i1

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 3:20 pm on October 29, 2014 Permalink | Reply
    Tags: , Biology, , , ,   

    From LBL: “New Lab Startup Afingen Uses Precision Method to Enhance Plants” 

    Berkeley Logo

    Berkeley Lab

    October 29, 2014
    Julie Chao (510) 486-6491

    Imagine being able to precisely control specific tissues of a plant to enhance desired traits without affecting the plant’s overall function. Thus a rubber tree could be manipulated to produce more natural latex. Trees grown for wood could be made with higher lignin content, making for stronger yet lighter-weight lumber. Crops could be altered so that only the leaves and certain other tissues had more wax, thus enhancing the plant’s drought tolerance, while its roots and other functions were unaffected.

    By manipulating a plant’s metabolic pathways, two scientists at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), Henrik Scheller and Dominique Loqué, have figured out a way to genetically rewire plants to allow for an exceptionally high level of control over the spatial pattern of gene expression, while at the same time boosting expression to very high levels. Now they have launched a startup company called Afingen to apply this technology for developing low-cost biofuels that could be cost-competitive with gasoline and corn ethanol.

    two
    Henrik Scheller (left) and Dominique Loque hold a tray of Arabidopsis Thaliana plants, which they used in their research. (Berkeley Lab photo)

    “With this tool we seem to have found a way to control very specifically what tissue or cell type expresses whatever we want to express,” said Scheller. “It’s a new way that people haven’t thought about to increase metabolic pathways. It could be for making more cell wall, for increasing the stress tolerance response in a specific tissue. We think there are many different applications.”

    Cost-competitive biofuels

    Afingen was awarded a Small Business Innovation Research (SBIR) grant earlier this year for $1.72 million to engineer switchgrass plants that will contain 20 percent more fermentable sugar and 40 percent less lignin in selected structures. The grant was provided under a new SBIR program at DOE that combines an SBIR grant with an option to license a specific technology produced at a national laboratory or university through DOE-supported research.

    “Techno-economic modeling done at (the Joint BioEnergy Institute, or JBEI) has shown that you would get a 23 percent reduction in the price of the biofuel with just a 20 percent reduction in lignin,” said Loqué. “If we could also increase the sugar content and make it easier to extract, that would reduce the price even further. But of course it also depends on the downstream efficiency.”

    Scheller and Loqué are plant biologists with the Department of Energy’s Joint BioEnergy Institute (JBEI), a Berkeley Lab-led research center established in 2007 to pursue breakthroughs in the production of cellulosic biofuels. Scheller heads the Feedstocks Division and Loqué leads the cell wall engineering group.

    The problem with too much lignin in biofuel feedstocks is that it is difficult and expensive to break down; reducing lignin content would allow the carbohydrates to be released and converted into fuels much more cost-effectively. Although low-lignin plants have been engineered, they grow poorly because important tissues lack the strength and structural integrity provided by the lignin. With Afingen’s technique, the plant can be manipulated to retain high lignin levels only in its water-carrying vascular cells, where cell-wall strength is needed for survival, but low levels throughout the rest of the plant.

    The centerpiece of Afingen’s technology is an “artificial positive feedback loop,” or APFL. The concept targets master transcription factors, which are molecules that regulate the expression of genes involved in certain biosynthetic processes, that is, whether certain genes are turned “on” or “off.” The APFL technology is a breakthrough in plant biotechnology, and Loqué and Scheller recently received an R&D 100 Award for the invention.

    An APFL is a segment of artificially produced DNA coded with instructions to make additional copies of a master transcription factor; when it is inserted at the start of a chosen biosynthetic pathway—such as the pathway that produces cellulose in fiber tissues—the plant cell will synthesize the cellulose and also make a copy of the master transcription factor that launched the cycle in the first place. Thus the cycle starts all over again, boosting cellulose production.

    The process differs from classical genetic engineering. “Some people distinguish between ‘transgenic’ and ‘cisgenic.’ We’re using only pieces of DNA that are already in that plant and just rearranging them in a new way,” said Scheller. “We’re not bringing in foreign DNA.”

    Other licensees and applications

    This breakthrough technique can also be used in fungi and for a wide variety of uses in plants, for example, to increase food crop yields or to boost production of highly specialized molecules used by the pharmaceutical and chemical industries. “It could also increase the quality of forage crops, such as hay fed to cows, by increasing the sugar content or improving the digestibility,” Loqué said.

    Another intriguing application is for biomanufacturing. By engineering plants to grow entirely new pharmaceuticals, specialty chemicals, or polymer materials, the plant essentially becomes a “factory.” “We’re interested in using the plant itself as a host for production,” Scheller said. “Just like you can upregulate pathways in plants that make cell walls or oil, you can also upregulate pathways that make other compounds or properties of interest.”

    Separately, two other companies are using the APFL technology. Tire manufacturer Bridgestone has a cooperative research and development agreement (CRADA) with JBEI to develop more productive rubber-producing plants. FuturaGene, a Brazilian paper and biomass company, has licensed the technology for exclusive use with eucalyptus trees and several other crops; APFL can enhance or develop traits to optimize wood quality for pulping and bioenergy applications.

    “The inventors/founders of Afingen made the decision to not compete for a license in fields of use that were of interest to other companies that had approached JBEI. This allowed JBEI to move the technology forward more quickly on several fronts,” said Robin Johnston, Berkeley Lab’s Acting Deputy Chief Technology Transfer Officer. “APFL is a very insightful platform technology, and I think only a fraction of the applications have even been considered yet.”

    Afingen currently has one employee—Ai Oikawa, a former postdoctoral researcher and now the director of plant engineering—and will be hiring three more in November. It is the third startup company to spin out of JBEI. The first two were Lygos, which uses synthetic biology tools to produce chemical compounds, and TeselaGen, which makes tools for DNA synthesis and cloning.

    See the full article here.

    A U.S. Department of Energy National Laboratory Operated by the University of California

    University of California Seal

    DOE Seal

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 6:24 pm on October 21, 2014 Permalink | Reply
    Tags: , Biology, Brain Studies,   

    From Princeton: “Immune proteins moonlight to regulate brain-cell connections” 

    Princeton University
    Princeton University

    October 21, 2014
    Morgan Kelly, Office of Communications

    When it comes to the brain, “more is better” seems like an obvious assumption. But in the case of synapses, which are the connections between brain cells, too many or too few can both disrupt brain function.

    Researchers from Princeton University and the University of California-San Diego (UCSD) recently found that an immune-system protein called MHCI, or major histocompatibility complex class I, moonlights in the nervous system to help regulate the number of synapses, which transmit chemical and electrical signals between neurons. The researchers report in the Journal of Neuroscience that in the brain MHCI could play an unexpected role in conditions such as Alzheimer’s disease, type II diabetes and autism.

    MHCI proteins are known for their role in the immune system where they present protein fragments from pathogens and cancerous cells to T cells, which are white blood cells with a central role in the body’s response to infection. This presentation allows T cells to recognize and kill infected and cancerous cells.

    In the brain, however, the researchers found that MHCI immune molecules are one of the only known factors that limit the density of synapses, ensuring that synapses form in the appropriate numbers necessary to support healthy brain function. MHCI limits synapse density by inhibiting insulin receptors, which regulate the body’s sugar metabolism and, in the brain, promote synapse formation.

    Tangled web

    web
    Researchers from Princeton University and the University of California-San Diego recently found that an immune-system protein called MHCI, or major histocompatibility complex class I, moonlights in the nervous system to help regulate the number of synapses, which transmit chemical and electrical signals between neurons. Pictured is a mouse hippocampal neuron studded with thousands of synaptic connections (yellow). The number and location of synapses — not too many or too few — is critical to healthy brain function. The researchers found that MHCI proteins, known for their role in the immune system, also are one of the only known factors that ensure synapse density is not too high. The protein does so by inhibiting insulin receptors, which promote synapse formation. (Image courtesy of Lisa Boulanger, Department of Molecular Biology)

    Senior author Lisa Boulanger, an assistant professor in the Department of Molecular Biology and the Princeton Neuroscience Institute (PNI), said that MHCI’s role in ensuring appropriate insulin signaling and synapse density raises the possibility that changes in the protein’s activity could contribute to conditions such Alzheimer’s disease, type II diabetes and autism. These conditions have all been associated with a complex combination of disrupted insulin-signaling pathways, changes in synapse density, and inflammation, which activates immune-system molecules such as MHCI.

    Patients with type II diabetes develop “insulin resistance” in which insulin receptors become incapable of responding to insulin, the reason for which is unknown, Boulanger said. Similarly, patients with Alzheimer’s disease develop insulin resistance in the brain that is so pronounced some have dubbed the disease “type III diabetes,” Boulanger said.

    “Our results suggest that changes in MHCI immune proteins could contribute to disorders of insulin resistance,” Boulanger said. “For example, chronic inflammation is associated with type II diabetes, but the reason for this link has remained a mystery. Our results suggest that inflammation-induced changes in MHCI could have consequences for insulin signaling in neurons and maybe elsewhere.”

    green
    This image of a neuron from a mouse hippocampus shows insulin receptors (green) and the protein calbindin (red). In this area of the brain, calbindin is present in dentate granule cells, which form synapses on MHCI-expressing cells. The extensive overlap (yellow) suggests that this neuron, which expresses insulin receptors, is a dentate granule cell neuron. (Image courtesy of Lisa Boulanger, Department of Molecular Biology)

    MHCI levels also are “dramatically altered” in the brains of people with Alzheimer’s disease, Boulanger said. Normal memory depends on appropriate levels of MHCI. Boulanger was senior author on a 2013 paper in the journal Learning and Memory that found that mice bred to produce less functional MHCI proteins exhibited striking changes in the function of the hippocampus, a part of the brain where some memories are formed, and had severe memory impairments.

    “MHCI levels are altered in the Alzheimer’s brain, and altering MHCI levels in mice disrupts memory, reduces synapse number and causes neuronal insulin resistance, all of which are core features of Alzheimer’s disease,” Boulanger said.

    Links between MHCI and autism also are emerging, Boulanger said. People with autism have more synapses than usual in specific brain regions. In addition, several autism-associated genes regulate synapse number, often via a signaling protein known as mTOR (mammalian target of rapamycin). In their study, Boulanger and her co-authors found that mice with reduced levels of MHCI had increased insulin-receptor signaling via the mTOR pathway, and, consequently, more synapses. When elevated mTOR signaling was reduced in MHCI-deficient mice, normal synapse density was restored.

    Thus, Boulanger said, MHCI and autism-associated genes appear to converge on the mTOR-synapse regulation pathway. This is intriguing given that inflammation during pregnancy, which alters MHCI levels in the fetal brain, may slightly increase the risk of autism in genetically predisposed individuals, she said.

    “Up-regulating MHCI is essential for the maternal immune response, but changing MHCI activity in the fetal brain when synaptic connections are being formed could potentially affect synapse density,” Boulanger said.

    Ben Barres, a professor of neurobiology, developmental biology and neurology at the Stanford University School of Medicine, said that while it is known that both insulin-receptor signaling increases synapse density, and MHCI signaling decreases it, the researchers are the first to show that MHCI actually affects insulin receptors to control synapse density.

    “The idea that there could be a direct interaction between these two signaling systems comes as a great surprise,” said Barres, who was not involved in the research. “This discovery not only will lead to new insight into how brain circuitry develops but to new insight into declining brain function that occurs with aging.”

    cer
    This section of adult mouse cerebellum shows insulin receptors (green) and calbindin (red), which in this case is present in the cerebellar neurons known as Purkinje cells. Insulin receptors are highly expressed in fibers that form synapses onto Purkinje cells, which express MHCI. Thus both in the cerebellum and hippocampus (previous image), insulin receptors are highly expressed in cells that form synapses onto MHCI-expressing neurons, which suggests MHCI and insulin receptors could interact, either directly or indirectly, in the living brain. (Image courtesy of Lisa Boulanger, Department of Molecular Biology)

    Particularly, the research suggests a possible functional connection between type II diabetes and Alzheimer’s disease, Barres said.

    “Type II diabetes has recently emerged as a risk factor for Alzheimer’s disease but it has not been clear what the connection is to the synapse loss experienced with Alzheimer’s disease,” he said. “Given that type II diabetes is accompanied by decreased insulin responsiveness, it may be that the MHCI signaling becomes able to overcome normal insulin signaling and contribute to synapse decline in this disease.”

    Research during the past 15 years has shown that MHCI lives a prolific double-life in the brain, Boulanger said. The brain is “immune privileged,” meaning the immune system doesn’t respond as rapidly or effectively to perceived threats in the brain. Dozens of studies have shown, however, that MHCI is not only present throughout the healthy brain, but is essential for normal brain development and function, Boulanger said. A 2013 paper from her lab published in the journal Molecular and Cellular Neuroscience showed that MHCI is even present in the fetal-mouse brain, at a stage when the immune system is not yet mature.

    “Many people thought that immune molecules like MHCI must be missing from the brain,” Boulanger said. “It turns out that MHCI immune proteins do operate in the brain — they just do something completely different. The dual roles of these proteins in the immune system and nervous system may allow them to mediate both harmful and beneficial interactions between the two systems.”

    The paper, MHC Class I Limits Hippocampal Synapse Density by Inhibiting Neuronal Insulin Receptor Signaling, was published Aug. 27 in the Journal of Neuroscience. Boulanger worked with Carolyn Tyler, a postdoctoral research fellow in PNI; Julianna Poole, who received her master’s degree in molecular biology from Princeton in 2014; Princeton senior Joseph Park; and Lawrence Fourgeaud and Tracy Dixon-Salazar, both at UCSD. The work was supported by the Whitehall Foundation; the Sloan Foundation; Cure Autism Now; the Princeton Neuroscience Institute Innovation Fund; the Silvio Varon Chair in Neuroregeneration at UCSD; Autism Speaks; and the National Science Foundation.

    See the full article here.

    About Princeton: Overview

    Princeton University is a vibrant community of scholarship and learning that stands in the nation’s service and in the service of all nations. Chartered in 1746, Princeton is the fourth-oldest college in the United States. Princeton is an independent, coeducational, nondenominational institution that provides undergraduate and graduate instruction in the humanities, social sciences, natural sciences and engineering.

    As a world-renowned research university, Princeton seeks to achieve the highest levels of distinction in the discovery and transmission of knowledge and understanding. At the same time, Princeton is distinctive among research universities in its commitment to undergraduate teaching.

    Today, more than 1,100 faculty members instruct approximately 5,200 undergraduate students and 2,600 graduate students. The University’s generous financial aid program ensures that talented students from all economic backgrounds can afford a Princeton education.

    Princeton Shield
    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 4:42 pm on October 21, 2014 Permalink | Reply
    Tags: , , , Biology,   

    From astrobio.net: “Scientists create possible precursor to life” 

    Astrobiology Magazine

    Astrobiology Magazine

    Oct 21, 2014
    University of Southern Denmark
    Contact Professor, Head of FLINT Center, Steen Rasmussen. Email: steen@sdu.dk. Mobile: +45 60112507

    How did life originate? And can scientists create life? These questions not only occupy the minds of scientists interested in the origin of life, but also researchers working with technology of the future. If we can create artificial living systems, we may not only understand the origin of life – we can also revolutionize the future of technology.

    pro
    Model of a protocell. Image by Janet Iwasa

    Protocells are the simplest, most primitive living systems, you can think of. The oldest ancestor of life on Earth was a protocell, and when we see, what it eventually managed to evolve into, we understand why science is so fascinated with protocells. If science can create an artificial protocell, we get a very basic ingredient for creating more advanced artificial life.

    However, creating an artificial protocell is far from simple, and so far no one has managed to do that. One of the challenges is to create the information strings that can be inherited by cell offspring, including protocells. Such information strings are like modern DNA or RNA strings, and they are needed to control cell metabolism and provide the cell with instructions about how to divide.

    Essential for life

    If one daughter cell after a division has a slightly altered information (maybe it provides a slightly faster metabolism), they may be more fit to survive. Therefore it may be selected and an evolution has started.

    Now researchers from the Center for Fundamental Living Technology (FLINT), Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, describe in the journal Europhysics Letters, how they, in a virtual computer experiment, have discovered information strings with peculiar properties.

    Professor and head of FLINT, Steen Rasmussen, says: “Finding mechanisms to create information strings are essential for researchers working with artificial life.”

    auto
    An autocatalytic network is a network of molecules, which catalyze each other’s production. Each molecule can be formed by at least one chemical reaction in the network, and each reaction can be catalyzed by at least one other molecule in the network. This process will create a network that exhibits a primitive form of metabolism and an information system that replicates itself from generation to generation. Credit University of Southern Denmark.

    Steen Rasmussen and his colleagues know they face two problems:

    Firstly long molecular strings are decomposed in water. This means that long information strings “break” quickly in water and turn into many short strings. Thus it is very difficult to maintain a population of long strings over time.

    Secondly, it is difficult to make these molecules replicate without the use of modern enzymes, whereas it is easier to make a so-called ligation. A ligation is to connect any combination of two shorter strings into a longer string, assisted by another matching longer string. Ligation is the mechanism used by the SDU-researchers.

    “In our computer simulation – our virtual molecular laboratory – information strings began to replicate quickly and efficiently as expected. However, we were struck to see that the system quickly developed an equal number of short and long information strings and further that a strong pattern selection on the strings had occurred. We could see that only very specific information patterns on the strings were to be seen in the surviving strings. We were puzzled: How could such a coordinated selection of strings occur, when we knew that we had not programmed it. The explanation had to be found in the way the strings interacted with each other”, explains Steen Rasmussen.

    It is like society

    According to Steen Rasmussen, a so-called self-organizing autocatalytic network was created in the virtual pot, into which he and his colleagues poured the ingredients for information strings.

    “An autocatalytic network works like a community; each molecule is a citizen who interacts with other citizens and together they help create a society”, explains Steen Rasmussen.

    This autocatalytic set quickly evolved into a state where strings of all lengths existed in equal concentrations, which is not what is usually found. Further, the selected strings had strikingly similar patterns, which is also unusual.

    “We might have discovered a process similar to the processes that initially sparked the first life. We of course don’t know if life actually was created this way – but it could have been one of the steps. Perhaps a similar process created sufficiently high concentrations of longer information strings when the first protocell was created”, explains Steen Rasmussen.

    Basis for new technology

    The mechanisms underlying the formation and selection of effective information strings are not only interesting for the researchers who are working to create protocells. They also have value to researchers working with tomorrow’s technology, like they do at the FLINT Center.

    “We seek ways to develop technology that’s based on living and life-like processes. If we succeed, we will have a world where technological devices can repair themselves, develop new properties and be re-used. For example a computer made of biological materials poses very different – and less environmentally stressful – requirements for production and disposal”, says Steen Rasmussen.

    Ref: http://epljournal.edpsciences.org/articles/epl/abs/2014/14/epl16388/epl16388.html

    See the full article here.

    NASA

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 3:04 pm on October 20, 2014 Permalink | Reply
    Tags: , Biology, ,   

    From LLNL: “Supercomputers link proteins to drug side effects” 


    Lawrence Livermore National Laboratory

    10/20/2014
    Kenneth K Ma, LLNL, (925) 423-7602, ma28@llnl.gov

    New medications created by pharmaceutical companies have helped millions of Americans alleviate pain and suffering from their medical conditions. However, the drug creation process often misses many side effects that kill at least 100,000 patients a year, according to the journal Nature.

    Lawrence Livermore National Laboratory researchers have discovered a high-tech method of using supercomputers to identify proteins that cause medications to have certain adverse drug reactions (ADR) or side effects. They are using high-performance computers (HPC) to process proteins and drug compounds in an algorithm that produces reliable data outside of a laboratory setting for drug discovery.

    The team recently published its findings in the journal PLOS ONE, titled Adverse Drug Reaction Prediction Using Scores Produced by Large-Scale Drug-Protein Target Docking on High-Performance Computer Machines.

    “We need to do something to identify these side effects earlier in the drug development cycle to save lives and reduce costs,” said Monte LaBute, a researcher from LLNL’s Computational Engineering Division and the paper’s lead author.

    It takes pharmaceutical companies roughly 15 years to bring a new drug to the market, at an average cost of $2 billion. A new drug compound entering Phase I (early stage) testing is estimated to have an 8 percent chance of reaching the market, according to the Food and Drug Administration (FDA).

    A typical drug discovery process begins with identifying which proteins are associated with a specific disease. Candidate drug compounds are combined with target proteins in a process known as binding to determine the drug’s effectiveness (efficacy) and/or harmful side effects (toxicity). Target proteins are proteins known to bind with drug compounds in order for the pharmaceutical to work.

    While this method is able to identify side effects with many target proteins, there are myriad unknown “off-target” proteins that may bind to the candidate drug and could cause unanticipated side effects.

    Because it is cost prohibitive to experimentally test a drug candidate against a potentially large set of proteins — and the list of possible off-targets is not known ahead of time — pharmaceutical companies usually only test a minimal set of off-target proteins during the early stages of drug discovery. This results in ADRs remaining undetected through the later stages of drug development, such as clinical trials, and possibly making it to the marketplace.

    There have been several highly publicized medications with off-target protein side effects that have reached the marketplace. For example, Avandia, an anti-diabetic drug, caused heart attacks in some patients; and Vioxx, an anti-inflammatory medication, caused heart attacks and strokes among certain patient populations. Both therapeutics were recalled because of their side effects.

    “There were no indications of side effects of these medications in early testing or clinical trials,” LaBute said. “We need a way to determine the safety of such therapeutics before they reach patients. Our work can help direct such drugs to patients who will benefit the most from them with the least amount of side effects.”

    LaBute and the LLNL research team tackled the problem by using supercomputers and information from public databases of drug compounds and proteins. The latter included protein databases of DrugBank, UniProt and Protein Data Bank (PDB), along with drug databases from the FDA and SIDER, which contain FDA-approved drugs with ADRs.

    The team examined 4,020 off-target proteins from DrugBank and UniProt. Those proteins were indexed against the PDB, which whittled the number down to 409 off-proteins that have high-quality 3D crystallographic X-ray diffraction structures essential for analysis in a computational setting.

    mp

    The 409 off-target proteins were fed into a Livermore HPC software known as VinaLC along with 906 FDA-approved drug compounds. VinaLC used a molecular docking matrix that bound the drugs to the proteins. A score was given to each combination to assess whether effective binding occurred.

    The binding scores were fed into another computer program and combined with 560 FDA-approved drugs with known side effects. An algorithm was used to determine which proteins were associated with certain side effects.

    The Lab team showed that in two categories of disorders — vascular disorders and neoplasms — their computational model of predicting side effects in the early stages of drug discovery using off-target proteins was more predictive than current statistical methods that do not include binding scores.

    In addition to LLNL ADR prediction methods performing better than current prediction methods, the team’s calculations also predicted new potential side effects. For example, they predicted a connection between a protein normally associated with cancer metastasis to vascular disorders like aneurysms. Their ADR predictions were validated by a thorough review of existing scientific data.

    “We have discovered a very viable way to find off-target proteins that are important for side effects,” LaBute said. “This approach using HPC and molecular docking to find ADRs never really existed before.”

    The team’s findings provide drug companies with a cost-effective and reliable method to screen for side effects, according to LaBute. Their goal is to expand their computational pharmaceutical research to include more off-target proteins for testing and eventually screen every protein in the body.

    “If we can do that, the drugs of tomorrow will have less side effects that can potentially lead to fatalities,” Labute said. “Optimistically, we could be a decade away from our ultimate goal. However, we need help from pharmaceutical companies, health care providers and the FDA to provide us with patient and therapeutic data.”

    two
    LLNL researchers Monte LaBute (left) and Felice Lightstone (right) were part of a Lab team that recently published an article in PLOS ONE detailing the use of supercomputers to link proteins to drug side effects. Photo by Julie Russell/LLNL

    The LLNL team also includes Felice Lightstone, Xiaohua Zhang, Jason Lenderman, Brian Bennion and Sergio Wong.

    See the full article here.

    LLNL Campus

    Operated by Lawrence Livermore National Security, LLC, for the Department of Energy’s National Nuclear Security
    Administration
    DOE Seal
    NNSA
    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 1:45 pm on October 17, 2014 Permalink | Reply
    Tags: , Biology,   

    From AAAS: “Would-be drug mimics ‘good’ cholesterol” 

    AAAS

    AAAS

    16 October 2014
    Robert F. Service

    A new drug candidate designed to mimic the body’s “good” cholesterol shows a striking ability in mice to lower cholesterol levels in the blood and dissolve artery-clogging plaques. What’s more, the compound works when given orally, rather than as an injection. If the results hold true in humans—a big if, given past failures at transferring promising treatments from mice—it could provide a new way to combat atherosclerosis, the biggest killer in developed countries.

    Although doctors already have effective cholesterol-lowering agents, such as statins, at their disposal, there’s room for improvement. Statins have significant side effects in some people and don’t always reduce cholesterol enough in others. “There is still plenty of heart disease out there even among people who take statins,” says Godfrey Getz, an experimental pathologist at the University of Chicago in Illinois.

    For that reason, researchers around the globe are searching for novel drugs that affect cholesterol levels in one of two ways. The first has been to reduce levels of low-density lipoprotein (LDL), commonly known as bad cholesterol, which has been associated with higher heart disease risk. This is the goal of statins, which block an enzyme involved in cholesterol production. The second strategy is to increase levels of good cholesterol, or high-density lipoprotein (HDL), which seems to boost heart health in people who have a lot of it. But producing HDL-raising drugs that prevent heart disease has proven difficult. In the body, a large protein called apolipoprotein A-I (apoA-I) wraps around fatty lipid molecules to create HDL particles that sop up LDL and ferry it to the liver where it is eliminated. So for several decades researchers have been designing and testing small protein fragments called peptides to see if they could mimic the behavior of apoA-I. One such peptide, known as 4F, did not reduce serum cholesterol levels, but it did shrink arterial plaques in mice, rabbits, and monkeys. And in an early clinical trial by researchers at Bruin Pharma Inc. in Beverly Hills, California, that was designed only to measure its safety in people, 4F didn’t appear to show any beneficial effect.

    pro
    Multiple copies of a four-armed peptide wrap around lipids to create particles that mimic the behavior of HDL, the “good” cholesterol.
    Y.Zhao et al., J. Am. Chem. Soc

    M. Reza Ghadiri, a chemist at the Scripps Research Institute in San Diego, California, and his colleagues took a slightly different tack, creating a peptide that mimics another part of the apoA-I protein than 4F does. Initial in vitro studies suggested the peptide formed HDL-like particles and sopped up LDL, an encouraging result that prompted them to push it further. Ghadiri and his Scripps colleagues have now tested their compound in mice that develop artery clogging plaques when fed a Western-style high-fat diet. One group of animals received the peptide intravenously. For another group, the researchers simply added the compound to the animals’ water, a strategy they considered unlikely to work, because the gut contains high amounts of proteases designed to chop proteins apart. To their surprise, in both groups, serum cholesterol levels dropped 40% from their previous levels within 2 weeks of starting to take the drug. And by 10 weeks, the number of artery-clogging lesions had been reduced by half, the team reports in the October issue of the Journal of Lipid Research. What remains puzzling, however, is that Ghadiri and his colleagues did not detect their peptides in the blood of their test animal. Ghadiri says this suggests that the new peptide may work by removing cholesterol precursors in the gut before they enter the bloodstream.

    “It’s a very interesting result,” Getz says. But he cautions that the work has been tested only in animals, and many therapies—including the closely related 4F peptide—fail to transfer to humans. That said, Getz notes that some of the initial promising results with this peptide and other apoA-I mimics offer hope that researchers may soon come up with novel drugs capable of dissolving artery-clogging plaques before they can wreak their havoc.

    See the full article here.

    The American Association for the Advancement of Science is an international non-profit organization dedicated to advancing science for the benefit of all people.

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 8:38 am on October 17, 2014 Permalink | Reply
    Tags: , Biology, , ,   

    From UC Berkeley: “New front in war on Alzheimer’s, other protein-folding diseases” 

    UC Berkeley

    UC Berkeley

    October 16, 2014
    Robert Sanders

    A surprise discovery that overturns decades of thinking about how the body fixes proteins that come unraveled greatly expands opportunities for therapies to prevent diseases such as Alzheimer’s and Parkinson’s, which have been linked to the accumulation of improperly folded proteins in the brain.

    “This finding provides a whole other outlook on protein-folding diseases; a new way to go after them,” said Andrew Dillin, the Thomas and Stacey Siebel Distinguished Chair of Stem Cell Research in the Department of Molecular and Cell Biology and Howard Hughes Medical Institute investigator at the University of California, Berkeley.

    br
    A cell suffering heat shock is like a country besieged, where attackers first sever lines of communications. The pat-10 gene helps repair communication to allow chaperones to treat misfolded proteins. (Andrew Dillin graphic)

    Dillin, UC Berkeley postdoctoral fellows Nathan A. Baird and Peter M. Douglas and their colleagues at the University of Michigan, The Scripps Research Institute and Genentech Inc., will publish their results in the Oct. 17 issue of the journal Science.

    Cells put a lot of effort into preventing proteins – which are like a string of beads arranged in a precise three-dimensional shape – from unraveling, since a protein’s activity as an enzyme or structural component depends on being properly shaped and folded. There are at least 350 separate molecular chaperones constantly patrolling the cell to refold misfolded proteins. Heat is one of the major threats to proteins, as can be demonstrated when frying an egg – the clear white albumen turns opaque as the proteins unfold and then tangle like spaghetti.

    Heat shock

    For 35 years, researchers have worked under the assumption that when cells undergo heat shock, as with a fever, they produce a protein that triggers a cascade of events that field even more chaperones to refold unraveling proteins that could kill the cell. The protein, HSF-1 (heat shock factor-1), does this by binding to promoters upstream of the 350-plus chaperone genes, upping the genes’ activity and launching the army of chaperones, which originally were called “heat shock proteins.”

    Injecting animals with HSF-1 has been shown not only to increase their tolerance of heat stress, but to increase lifespan.

    Because an accumulation of misfolded proteins has been implicated in aging and in neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases, scientists have sought ways to artificially boost HSF-1 in order to reduce the protein plaques and tangles that eventually kill brain cells. To date, such boosters have extended lifespan in lab animals, including mice, but greatly increased the incidence of cancer.

    Dillin’s team found in experiments on the nematode worm C. elegans that HSF-1 does a whole lot more than trigger release of chaperones. An equal if not more important function is to stabilize the cell’s cytoskeleton, which is the highway that transports essential supplies – healing chaperones included – around the cell.

    “We are suggesting that, rather than making more of HSF-1 to prevent diseases like Huntington’s, we should be looking for ways to make the actin cytoskeleton better,” Dillin said. Such tactics might avoid the carcinogenic side effects of upping HSF-1.

    Dillin is codirector of the Paul F. Glenn Center for Aging Research, a new collaboration between UC Berkeley and UC San Francisco supported by the Glenn Foundation for Medical Research. Center investigators will study the many ways that proteins malfunction within cells, ideally paving the way for novel treatments for neurodegenerative diseases.

    A cell at war

    Dillin compares a cell experiencing heat shock to a country under attack. In a war, an aggressor first cuts off all communications, such as roads, train and bridges, which prevents the doctors from treating the wounded. Similarly, heat shock disrupts the cytoskeletal highway, preventing the chaperone “doctors” from reaching the patients, the misfolded proteins.

    chap
    Chaperones help newborn proteins (polypeptides) fold properly, but also fix misfolded proteins.

    “We think HSF-1 not only makes more chaperones, more doctors, but also insures that the roadways stay intact to keep everything functional and make sure the chaperones can get to the sick and wounded warriors,” he said.

    The researchers found specifically that HSF-1 up-regulates another gene, pat-10, that produces a protein that stabilizes actin, the building blocks of the cytoskeleton.

    By boosting pat-10 activity, they were able to cure worms that had been altered to express the Huntington’s disease gene, and also extend the lifespan of normal worms.

    Dillin suspects that HSF-1’s main function is, in fact, to protect the actin cytoskeleton. He and his team mutated HSF-1 so that it no longer boosted chaperones, demonstrating, he said, that “you can survive heat shock with the normal level of heat shock proteins, as long as you make your cytoskeleton work better.”

    He noted that the team’s results – that boosting chaperones is not essential to surviving heat stress – were so contradictory to current thinking that “I made my post-docs’ lives hell for three years” insisting on more experiments to rule out errors. Yet, when Dillin presented the results recently to members of the protein-folding community, he said the first reaction of many was, “That makes perfect sense.”

    Dillin’s colleagues include Milos S. Simic and Suzanne C. Wolff of UC Berkeley, Ana R. Grant of the University of Michigan in Ann Arbor, James J. Moresco and John R. Yates III of Scripps in La Jolla, Calif., and Gerard Manning of Genentech, South San Francisco, Calif. The work is funded by the Howard Hughes Medical Institute as well as by the National Institute of General Medical Sciences (8 P41 GM103533-17) and National Institute on Aging (R01AG027463-04) of the National Institutes of Health.

    See the full article here.

    Founded in the wake of the gold rush by leaders of the newly established 31st state, the University of California’s flagship campus at Berkeley has become one of the preeminent universities in the world. Its early guiding lights, charged with providing education (both “practical” and “classical”) for the state’s people, gradually established a distinguished faculty (with 22 Nobel laureates to date), a stellar research library, and more than 350 academic programs.

    UC Berkeley Seal

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 9:04 pm on October 16, 2014 Permalink | Reply
    Tags: , Biology, , ,   

    From LLNL: “Lab, UC Davis partner to personalize cancer medications” 


    Lawrence Livermore National Laboratory

    10/16/2014
    Stephen P Wampler, LLNL, (925) 423-3107, wampler1@llnl.gov

    Buoyed by several dramatic advances, Lawrence Livermore National Laboratory scientists think they can tackle biological science in a way that couldn’t be done before.

    Over the past two years, Lab researchers have expedited accelerator mass spectrometer sample preparation and analysis time from days to minutes and moved a complex scientific process requiring accelerator physicists into routine laboratory usage.

    Ken Turteltaub, the leader of the Lab’s Biosciences and Biotechnology Division, sees the bio AMS advances as allowing researchers to undertake quantitative assessments of complex biological pathways.

    “We are hopeful that we’ll be able to quantify the individual steps in a metabolic pathway and be able to measure indicators of disease processes and factors important to why people differ in responses to therapeutics, to diet and other factors,” Turteltaub said.

    Graham Bench, the director of the Lab’s Center for Accelerator Mass Spectrometry, anticipates the upgrades will enable Lab researchers “to produce high-density data sets and tackle novel biomedical problems that in the past couldn’t be addressed.”

    Ted Ognibene, a chemist who has worked on AMS for 15 years and who co-developed the technique that accommodates liquid samples, also envisions new scientific work coming forth.

    two
    Ted Ognibene (left), a chemist who co-developed the technique that accommodates liquid samples for accelerator mass spectrometry, peers with biomedical scientist Mike Malfatti at the new biological AMS instrument that has been installed in the Laboratory’s biomedical building. Photo by George Kitrinos

    “We previously had the capability to detect metabolites, but now with the ability to see our results almost immediately for a fraction of the cost, it’s going to enable a lot more fundamental and new science to be done,” Ognibene said.

    Biological AMS is a technique in which carbon-14 is used as a tag to study with extreme precision and sensitivity complex biological processes, such as cancer, molecular damage, drug and toxin behavior, nutrition and other areas.

    Among the biomedical studies that will be funded through the five-year, $7.8 million National Institutes of Health grant for biological AMS work is one to try to develop a test to predict how people will respond to chemotherapeutic drugs.

    Another research project seeks to create an assay that is so sensitive that it can detect one cancer cell among one million healthy cells. If this work is successful, it could be possible to evaluate the metastasis potential of different primary human cancer cells.

    Lab biomedical scientist Mike Malfatti and two researchers - Paul Henderson, an associate professor, and Chong-Xian Pan, a medical oncologist — from the University of California, Davis Comprehensive Cancer Center, are using the AMS in a human trial with 50 patients to see how cancer patients respond or don’t respond to the chemotherapeutic drug carboplatin. This drug kills cancer cells by binding to DNA, and is toxic to rapidly dividing cells.

    The three researchers have the patients take a microdose of carboplatin — about 1/100th of a therapeutic dose — that has no toxicity or therapeutic value to evaluate how effectively the drug will bind to a person’s DNA during full dose treatment.

    Within a few days of patients receiving the microdose, the degree of drug binding is checked by blood sample, in which the DNA is isolated from white blood cells, or by tumor biopsy, in which the DNA is isolated from the tumor cells.

    The carboplatin dose is prepared with a carbon-14 tag. The DNA sample is analyzed using AMS and the instrument quantifies the carbon-14 level, with a high level of carbon-14 indicating a high level of drug binding to the DNA.

    “A high degree of binding indicates that you have a high probability of a favorable response to the drug,” Malfatti said. “Conversely, a low degree of binding means it is likely the person’s body won’t respond to the treatment.

    “If we can identify which people will respond to which chemotherapeutic drug, we can tailor the treatment to the individual.

    “There are many negative side effects associated with chemotherapy, such as nausea, loss of appetite, loss of hair and even death. We don’t want someone to receive chemotherapy that’s not going to help them, yet leave them with these negative side effects,” he added.

    Malfatti, Henderson and Pan also are using the AMS in pre-clinical studies to investigate the resistance or receptivity of other commonly used chemotherapeutic agents such as cisplatin, oxaliplatin and gemcitabine.

    Another team of researchers, led by Gaby Loots, a Lab biomedical scientist and an associate professor at the University of California, Merced, wants to use AMS to measure cancer cells labeled with carbon-14 to study the cancer cells’ migration to healthy tissues to determine how likely they are to form metastatic tumors.

    While today’s standard methods can detect tumors that are comprised of thousands of cells, the team would like to develop an assay with a thousand-fold better resolution – to detect one cancer cell among one million healthy ones.

    “The sensitivity of AMS allows us to develop more accurate, quantitative assays with single-cell resolution. Is the cancer completely gone, or do we see one cell worth of cancer DNA?” Loots noted.

    Some of the questions the team would like to answer are: 1) why certain cells metastasize? 2) how do cells metastasize? 3) what new methods can be developed to prevent metastasis?

    “Tumors shed cells all the time that enter our circulation. We would like to find ways to prevent the circulating tumor cells from forming metastatic tumors,” Loots continued.

    As a part of their research, the team members hope to determine whether cancer cells with stem-cell-like properties form more aggressive tumors.

    “We’re going to separate the cancer cells into stem-cell-like and non-stem-cell-like populations and seek to determine if they behave differently,” said Loots, who is working with fellow Lab biomedical scientists Nick Hum and Nicole Collette.

    See the full article here.

    LLNL Campus

    Operated by Lawrence Livermore National Security, LLC, for the Department of Energy’s National Nuclear Security
    Administration
    DOE Seal
    NNSA
    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 6:09 pm on October 16, 2014 Permalink | Reply
    Tags: , , Biology, ,   

    From Johns Hopkins: “Chemical derived from broccoli sprouts shows promise in treating autism” 

    Johns Hopkins
    Johns Hopkins University

    October 13, 2014
    Catherine Kolf

    Many trial participants who received daily dose of sulforaphane show improvements in social interaction, verbal communication, researchers say

    Results of a small clinical trial suggest that a chemical derived from broccoli sprouts—and best known for claims that it can help prevent certain cancers—may ease classic behavioral symptoms in those with autism spectrum disorders.

    bro

    The study, a joint effort by scientists at MassGeneral Hospital for Children and the Johns Hopkins University School of Medicine, involved 40 teenage boys and young men, ages 13 to 27, with moderate to severe autism.

    In a report published online in the journal Proceedings of the National Academy of Sciences, the researchers say that many of those who received a daily dose of the chemical sulforaphane experienced substantial improvements in their social interaction and verbal communication, along with decreases in repetitive, ritualistic behaviors, compared to those who received a placebo.

    “We believe that this may be preliminary evidence for the first treatment for autism that improves symptoms by apparently correcting some of the underlying cellular problems,” says Paul Talalay, a professor of pharmacology and molecular sciences at the Johns Hopkins University School of Medicine who has researched these vegetable compounds for the past 25 years.

    “We are far from being able to declare a victory over autism, but this gives us important insights into what might help,” says co-investigator Andrew Zimmerman, a professor of pediatric neurology at UMass Memorial Medical Center.

    Autism experts estimate that the group of disorders affects 1 to 2 percent of the world’s population, with a much higher incidence in boys than in girls. Its behavioral symptoms, such as poor social interaction and verbal communication, are well known and were first described 70 years ago by Leo Kanner, the founder of pediatric psychiatry at Johns Hopkins University.

    Unfortunately, the root causes of autism remain elusive, though progress has been made, Talalay says, in describing some of the biochemical and molecular abnormalities that tend to accompany the disorders. Many of these are related to the efficiency of energy generation in cells. He says that studies show that the cells of those on the autism spectrum often have high levels of oxidative stress, the buildup of harmful, unintended byproducts from the cell’s use of oxygen that can cause inflammation, damage DNA, and lead to cancer and other chronic diseases.

    In 1992, Talalay’s research group discovered that sulforaphane has some ability to bolster the body’s natural defenses against oxidative stress, inflammation, and DNA damage. In addition, the chemical later turned out to improve the body’s heat-shock response—a cascade of events used to protect cells from the stress caused by high temperatures, including those experienced when people have fever.

    Intriguingly, he says, about 50% of parents report that their children’s autistic behavior improves noticeably when they have a fever, then reverts back when the fever is gone. In 2007, Zimmerman, a principal collaborator in the current study, tested this anecdotal trend clinically and found it to be true, though a mechanism for the fever effect was not identified.

    Because fevers, like sulforaphane, initiate the body’s heat-shock response, Zimmerman and Talalay wondered if sulforaphane could cause the same temporary improvement in autism that fevers do. The current study was designed to find out.

    Before the start of the trial, the patients’ caregivers and physicians filled out three standard behavioral assessments: the Aberrant Behavior Checklist (ABC), the Social Responsiveness Scale (SRS), and the Clinical Global Impressions-Improvement scale (CGI-I). The assessments measure sensory sensitivities, ability to relate to others, verbal communication skills, social interactions, and other behaviors related to autism.

    Twenty-six of the subjects were randomly selected to receive, based on their weight, 9 to 27 milligrams of sulforaphane daily, and 14 received placebos. Behavioral assessments were again completed at four, 10, and 18 weeks while treatment continued. A final assessment was completed for most of the participants four weeks after the treatment had stopped.

    Most of those who responded to sulforaphane showed significant improvements by the first measurement at four weeks and continued to improve during the rest of the treatment. After 18 weeks of treatment, the average ABC and SRS scores of those who received sulforaphane had decreased 34 and 17 percent, respectively, with improvements in bouts of irritability, lethargy, repetitive movements, hyperactivity, awareness, communication, motivation, and mannerisms.

    After 18 weeks of treatment, according to the CGI-I scale, sulforaphane recipients experienced noticeable improvements in social interaction (46%), aberrant behaviors (54%), and verbal communication (42%).

    Talalay notes that the scores of those who took sulforaphane trended back toward their original values after they stopped taking the chemical, just like what happens to those who experience improvements during a fever. “It seems like sulforaphane is temporarily helping cells to cope with their handicaps,” he says.

    Zimmerman adds that before they learned which subjects got the sulforaphane or placebo, the impressions of the clinical team—including parents—were that 13 of the participants noticeably improved. For example, some treated subjects looked them in the eye and shook their hands, which they had not done before. They found out later that all 13—half of the treatment group—had been taking sulforaphane.

    Talalay cautions that the levels of sulforaphane precursors present in different varieties of broccoli are highly variable. Furthermore, the capacity of individuals to convert these precursors to active sulforaphane also varies greatly. It would be very difficult to achieve the levels of sulforaphane used in this study by eating large amounts of broccoli or other cruciferous vegetables, he notes.

    See the full article here.

    Johns Hopkins Campus

    The Johns Hopkins University opened in 1876, with the inauguration of its first president, Daniel Coit Gilman. “What are we aiming at?” Gilman asked in his installation address. “The encouragement of research … and the advancement of individual scholars, who by their excellence will advance the sciences they pursue, and the society where they dwell.”

    The mission laid out by Gilman remains the university’s mission today, summed up in a simple but powerful restatement of Gilman’s own words: “Knowledge for the world.”

    What Gilman created was a research university, dedicated to advancing both students’ knowledge and the state of human knowledge through research and scholarship. Gilman believed that teaching and research are interdependent, that success in one depends on success in the other. A modern university, he believed, must do both well. The realization of Gilman’s philosophy at Johns Hopkins, and at other institutions that later attracted Johns Hopkins-trained scholars, revolutionized higher education in America, leading to the research university system as it exists today.

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
c
Compose new post
j
Next post/Next comment
k
Previous post/Previous comment
r
Reply
e
Edit
o
Show/Hide comments
t
Go to top
l
Go to login
h
Show/Hide help
shift + esc
Cancel
Follow

Get every new post delivered to your Inbox.

Join 348 other followers

%d bloggers like this: