BreakThrough Digest Medical News |
- Sensor detects glucose in saliva and tears for diabetes testing
- Nanoparticles reboot blood flow in brain
- Field guide to the Epstein-Barr virus charts viral paths toward cancer
- Key to burning fat faster discovered
| Sensor detects glucose in saliva and tears for diabetes testing Posted: 22 Aug 2012 09:00 PM PDT
Researchers have created a new type of biosensor that can detect minute concentrations of glucose in saliva, tears and urine and might be manufactured at low cost because it does not require many processing steps to produce.
“It’s an inherently non-invasive way to estimate glucose content in the body,” said Jonathan Claussen, a former Purdue doctoral student and now a research scientist at the U.S. Naval Research Laboratory. “Because it can detect glucose in the saliva and tears, it’s a platform that might eventually help to eliminate or reduce the frequency of using pinpricks for diabetes testing. We are proving its functionality.” Claussen and Purdue doctoral student Anurag Kumar led the project, working with Timothy Fisher, a Purdue professor of mechanical engineering, D. Marshall Porterfield, a professor of agricultural and biological engineering, and other researchers at the university’s Birck Nanotechnology Center. Findings are detailed in a research paper appearing online this week in the journal Advanced Functional Materials. “Most sensors typically measure glucose in blood,” Claussen said. “Many in the literature aren’t able to detect glucose in tears and the saliva. What’s unique is that we can sense in all four different human serums: the saliva, blood, tears and urine. And that hasn’t been shown before.” The paper, featured on the journal’s cover, was written by Claussen, Kumar, Fisher, Porterfield, and Purdue researchers David B. Jaroch, M. Haseeb Khawaja, and Allison B. Hibbard. The sensor has three main parts: layers of nanosheets resembling tiny rose petals made of a material called graphene, which is a single-atom-thick film of carbon; platinum nanoparticles; and the enzyme glucose oxidase. Each petal contains a few layers of graphene stacked on each other. The edges of the petals have dangling, incomplete chemical bonds, defects where the platinum nanoparticles can attach. Electrodes are formed by combining the nanosheet petals and platinum nanoparticles. Then the glucose oxidase attaches to the platinum nanoparticles. The enzyme converts glucose to peroxide, which generates a signal on the electrode. “Typically, when you want to make a nanostructured biosensor you have to use a lot of processing steps before you reach the final biosensor product,” Kumar said. “That involves lithography, chemical processing, etching and other steps. The good thing about these petals is that they can be grown on just about any surface, and we don’t need to use any of these steps, so it could be ideal for commercialization.” In addition to diabetes testing, the technology might be used for sensing a variety of chemical compounds to test for other medical conditions. “Because we used the enzyme glucose oxidase in this work, it’s geared for diabetes,” Claussen said. “But we could just swap out that enzyme with, for example, glutemate oxidase, to measure the neurotransmitter glutamate to test for Parkinson’s and Alzheimer’s, or ethanol oxidase to monitor alcohol levels for a breathalyzer. It’s very versatile, fast and portable.” The technology is able to detect glucose in concentrations as low as 0.3 micromolar, far more sensitive than other electrochemical biosensors based on graphene or graphite, carbon nanotubes and metallic nanoparticles, Claussen said “These are the first findings to report such a low sensing limit and at the same time such a wide sensing range,” he said. The sensor is able to distinguish between glucose and signals from other compounds that often cause interference in sensors: uric acid, ascorbic acid and acetaminophen, which are commonly found in the blood. Unlike glucose, those compounds are said to be electroactive, which means they generate an electrical signal without the presence of an enzyme. Glucose by itself doesn’t generate a signal but must first react with the enzyme glucose oxidase. Glucose oxidase is used in commercial diabetes test strips for conventional diabetes meters that measure glucose with a finger pinprick. ### The research has been based at Purdue’s Birck Nanotechnology Center at the university’s Discovery Park. The research has been funded by the U.S. Office of Naval Research and the National Science Foundation. Writer: Emil Venere, 765-494-4709, venere@purdue.edu Sources: Jonathan Claussen, 202-767-3560, jonathan.claussen@gmail.com Anurag Kumar, kumar.anuragsharma@gmail.com Timothy Fisher, 765-494-5627, tsfisher@purdue.edu D. Marshall Porterfield, 765-494-1190, porterf@purdue.edu Related websites:
Timothy Fisher: https://engineering.purdue.edu/ME/People/ptProfile?id=28558 IMAGE CAPTION:
These color-enhanced scanning electron microscope images show nanosheets resembling tiny rose petals. The nanosheets are key components of a new type of biosensor that can detect minute concentrations of glucose in saliva, tears and urine. The technology might eventually help to eliminate or reduce the frequency of using pinpricks for diabetes testing. (Jeff Goecker, Purdue University) A publication-quality image is available at http://news.uns.purdue.edu/images/2012/fisher-sensor.jpg ABSTRACT
Nanostructuring Platinum Nanoparticles on Multilayered Graphene Petal Nanosheets for Electrochemical Biosensing Jonathan C. Claussen2, Anurag Kumar1,David B. Jaroch3, M. Haseeb Khawaja1, Allison B. Hibbard1, D. Marshall Porter?eld,2, 3, and Timothy S. Fisher1 1 Birck Nanotechnology Center, School of Mechanical Engineering, Purdue University 2Birck Nanotechnology Center, Department of Agricultural and Biological Engineering, Purdue University School of Mechanical Engineering 3Birck Nanotechnology Center, Weldon School of Biomedical Engineering, Purdue University Hybridization of nanoscale metals and carbon nanotubes into composite nanomaterials has produced some of the best-performing sensors to date. The challenge remains to develop scalable nanofabrication methods that are amenable to the development of sensors with broad sensing ranges. A scalable nanostructured biosensor based on multilayered graphene petal nanosheets (MGPNs), Pt nanoparticles, and a biorecognition element (glucose oxidase) is presented. The combination of zero-dimensional nano-particles on a two-dimensional support that is arrayed in the third dimension creates a sensor platform with exceptional characteristics. The versatility of the biosensor platform is demonstrated by altering biosensor performance (i.e., sensitivity, detection limit, and linear sensing range) through changing the size, density, and morphology of electrodeposited Pt nanoparticles on the MGPNs. This work enables a robust sensor design that demonstrates exceptional performance with enhanced glucose sensitivity (0.3 µM detection limit, 0.01 mM linear sensing range), a long stable shelf-life (> 1 month), and a high selectivity over electroactive, interfering species commonly found in human serum samples. Contact: Emil Venere |
| Nanoparticles reboot blood flow in brain Posted: 22 Aug 2012 09:00 PM PDT A nanoparticle developed at Rice University and tested in collaboration with Baylor College of Medicine (BCM) may bring great benefits to the emergency treatment of brain-injury victims, even those with mild injuries.
Combined polyethylene glycol-hydrophilic carbon clusters (PEG-HCC), already being tested to enhance cancer treatment, are also adept antioxidants. In animal studies, injections of PEG-HCC during initial treatment after an injury helped restore balance to the brain’s vascular system. The results were reported this month in the American Chemical Society journal ACS Nano. A PEG-HCC infusion that quickly stabilizes blood flow in the brain would be a significant advance for emergency care workers and battlefield medics, said Rice chemist and co-author James Tour. “This might be a first line of defense against reactive oxygen species (ROS) that are always overstimulated during a medical trauma, whether that be to an accident victim or an injured soldier,” said Tour, Rice’s T.T. and W.F. Chao Chair in Chemistry as well as a professor of mechanical engineering and materials science and of computer science. “They’re certainly exacerbated when there’s trauma with massive blood loss.” In a traumatic brain injury, cells release an excessive amount of an ROS known as superoxide (SO) into the blood. Superoxides are toxic free radicals, molecules with one unpaired electron, that the immune system normally uses to kill invading microorganisms. Healthy organisms balance SO with superoxide dismutase (SOD), an enzyme that neutralizes it. But even mild brain trauma can release superoxides at levels that overwhelm the brain’s natural defenses. “Superoxide is the most deleterious of the reactive oxygen species, as it’s the progenitor of many of the others,” Tour said. “If you don’t deal with SO, it forms peroxynitrite and hydrogen peroxide. SO is the upstream precursor to many of the downstream problems.” SO affects the autoregulatory mechanism that manages the sensitive circulation system in the brain. Normally, vessels dilate when blood pressure is low and constrict when high to maintain an equilibrium, but a lack of regulation can lead to brain damage beyond what may have been caused by the initial trauma. “There are many facets of brain injury that ultimately determine how much damage there will be,” said Thomas Kent, the paper’s co-author, a BCM professor of neurology and chief of neurology at the Michael E. DeBakey Veterans Affairs Medical Center in Houston. “One is the initial injury, and that’s pretty much done in minutes. But a number of things that happen later often make things worse, and that’s when we can intervene.” Kent cited as an example the second burst of free radicals that can occur after post-injury resuscitation. “That’s what we can treat: the further injury that happens because of the necessity of restoring somebody’s blood pressure, which provides oxygen that leads to more damaging free radicals.” In tests, the researchers found PEG-HCC nanoparticles immediately and completely quenched superoxide activity and allowed the autoregulatory system to quickly regain its balance. Tour said ROS molecules readily combine with PEG-HCCs, generating “an innocuous carbon double bond, so it’s really radical annihilation. There’s no such mechanism in biology.” While an SOD enzyme can alter only one superoxide molecule at a time, a single PEG-HCC about the size of a large protein at 2-3 nanometers wide and 30-40 nanometers long can quench hundreds or thousands. “This is an occasion where a nano-sized package is doing something that no small drug or protein could do, underscoring the efficacy of active nano-based drugs.” “This is the most remarkably effective thing I’ve ever seen,” Kent said. “Literally within minutes of injecting it, the cerebral blood flow is back to normal, and we can keep it there with just a simple second injection. In the end, we’ve normalized the free radicals while preserving nitric oxide (which is essential to autoregulation). These particles showed the antioxidant mechanism we had previously identified as predictive of effectiveness.” The first clues to PEG-HCC’s antioxidant powers came during nanoparticle toxicity studies with the MD Anderson Cancer Center. “We noticed they lowered alkaline phosphatase in the liver,” Tour said. “One of our Baylor colleagues saw this and said, ‘Hey, this looks like it’s actually causing the liver cells to live longer than normal.’ “Oxidative destruction of liver cells is normal, so that got us to thinking these might be really good radical scavengers,” Tour said. Kent said the nanoparticles as tested showed no signs of toxicity, but any remaining concerns should be answered by further tests. The researchers found the half-life of PEG-HCCs in the blood ? the amount of time it takes for half the particles to leave the body ? to be between two and three hours. Tests with different cell types in vitro showed no toxicity, he said. The research has implications for stroke victims and organ transplant patients as well, Tour said. Next, the team hopes to have another lab replicate its positive results. “We’ve repeated it now three times, and we got the same results, so we’re sure this works in our hands,” Kent said. ### First authors of the paper are BCM graduate student Brittany Bitner, Rice graduate student Daniela Marcano and former Rice postdoctoral researcher Jacob Berlin, now an assistant professor of molecular medicine at the Beckman Research Institute of the City of Hope, Duarte, Calif. Co-authors are all at BCM: Roderic Fabian, associate professor of neurology; Claudia Robertson, professor of neurosurgery; Leela Cherian, research instructor of neurosurgery; Mary Dickinson, associate professor of molecular physiology; Robia Pautler, associate professor of molecular physiology; and James Culver, a graduate student in molecular physiology. The research was funded by the Department of Defense’s Mission Connect Mild Traumatic Brain Injury Consortium, the National Science Foundation, the National Institutes of Health and the National Heart, Lung and Blood Institute. This news release can be found online at http://news.rice.edu/2012/08/23/nanoparticles-reboot-blood-flow-in-brain/ Read the abstract at http://pubs.acs.org/doi/abs/10.1021/nn302615f Follow Rice News and Media Relations via Twitter @RiceUNews Related Links: Tour Group: http://www.jmtour.com/ Image for download: http://news.rice.edu/wp-content/uploads/2012/08/soldier.jpg New research funded primarily by the Department of Defense would help emergency care workers and battlefield medics stabilize blood flow in the brains of traumatic injury victims. Rice University and Baylor College of Medicine in Houston developed a nanoparticle-based antioxidant that quickly quenches free radicals that interfere with regulation of the brain’s vascular system. Rice University contacts: Mike Williams Baylor College of Medicine contact: |
| Field guide to the Epstein-Barr virus charts viral paths toward cancer Posted: 22 Aug 2012 09:00 PM PDT Researchers from The Wistar Institute and Memorial Sloan-Kettering Cancer Center (MSKCC) have teamed to publish the first annotated atlas of the Epstein-Barr virus genome, creating the most comprehensive study of how the viral genome interacts with its human host during a latent infection. Epstein-Barr virus (EBV), which is thought to be responsible for one percent of all human cancers, establishes a latent infection in nearly 100 percent of infected adult humans.
The atlas is designed to guide researchers toward new means of creating therapies against EBV-latent infection and the cancers associated with latent EBV infection, such as B cell lymphomas, gastric carcinomas, and nasopharyngeal carcinomas. The project provides the best look yet at how EBV interacts with the genes and proteins of its host cells.A representation of the annotated EBV “epigenome,” listing the protein and chemical decorations added to the EBV DNA that get passed along to new copies of the EBV virus. As a supplement to the EBV genome?the characterization of the virus’s genes?the atlas describes the epigenome?all the protein and chemical decorations added to the EBV DNA that get passed along to new copies of the EBV virus?and the transcriptome?the catalog of all the RNA transcripts created from EBV DNA, which are either coded into protein or serve to regulate DNA directly. The researchers discovered numerous new points of interaction between viral DNA and its host, highlighting the extensive coevolution of the virus and pointing toward possible targets for future cancer and anti-viral drugs. “Epstein-Barr is a human tumor virus associated with many carcinomas and lymphomas and how it is regulated is something we need to understand in detail,” said Paul Lieberman, Ph.D., the McNeil Professor of Molecular Medicine and Translational Research and director of Wistar’s Center for Chemical Biology and Translational Medicine. “The EBV atlas is an instructive guide for how to analyze an entire, intact genome.” The published report is available online now through the journal Cell Host & Microbe, and all of the raw and processed data that went into creating the atlas are freely available online through the Lieberman laboratory. “EBV is parasitic organism, but it is a self-contained organism that needs to obey the general rules of regulation and dynamics if it is going to reproduce and survive,” Lieberman said. “Everything is integrated in this one small genome, containing just 90 or so genes, but the elements that govern its survival apply to our genomes and those of many other organisms.” EBV infection occurs within epithelial cells of the throat, sinuses, and gut, but long-term residence occurs within long-lived memory B cells, the white blood cells of the immune system that remember pathogens and produce antibodies. Once inside cells, the viral DNA becomes, in effect, a minichromosome, thriving alongside human chromosomes and relying on the same gene reading and regulating mechanisms that human chromosomes use. As the virus sets up shop in the host cell, it can?if other conditions in the cell are permissive?cause the cell to become cancerous. Indeed, the atlas project confirms that the most “active” EBV genomes are often found in the most cancerous cell lines. The EBV atlas describes over 60 human transcription factors?human proteins that bind to the EBV genome and control how viral genes are regulated?many of which were previously unknown to interact with EBV. One newly-identified factor, Pax5, is especially interesting, according to Lieberman, because it is a gene that’s largely responsible for how B cells rearrange its chromosomes to develop new, unique antibodies. The EBV atlas project was instigated by MSKCC’s Aaron Arvey, Ph.D., while he was a doctoral student in the laboratory of study co-author Christina Leslie, Ph.D., a member of the Sloan-Kettering Institute’s Computational Biology Program. While analyzing data for the Encyclopedia of DNA Elements (ENCODE) Consortium, a multi-institutional project of the National Human Genome Research Institute to build a comprehensive list of all the ways human cells interact with and regulate their genes, Arvey also collected data related to EBV, which maintains a stable infection in the cells he had studied.. At his urging, the Leslie lab began a collaboration with the Lieberman lab at Wistar, which has studied the virus and its relationship to cancer for over two decades. The project involved studying 700 sets of genetic data from over 50 separate lines of B cells infected with EBV. The Leslie lab took on the work of developing collecting the data, while the Lieberman lab conducted the experimental validation to back up their findings. “The vast majority of data analyzed in the paper comes from large-scale next-generation sequencing experiments carried out by projects such as ENCODE and HapMap,” said Leslie. “Our study depends critically on the unbiased nature of sequencing data?since we could detect transcription factor binding sites and histone modifications along the EBV genome as well as transcripts of viral origin from sequencing experiments in human cells?as well as the availability of large public data sets.” While not affiliated with ENCODE directly, the EBV atlas project benefited greatly from the data generated through the project. According to Leslie, the fact that they could derive such a detailed characterization of the EBV epigenome and transcriptome largely from public data underscores the value of these big data resources. ### This research was funded through support from the National Cancer Institute, National Human Genome Research Institute, and National Institute of Allergy and Infectious Diseases, all of which are components within the National Institutes of Health. Wistar co-authors include Italo Tempera, Ph.D., Kevin Tsai, Horng-Shen Chen, Ph.D., and Nadezhda Tikhmyanova, Ph.D., and Michael Klinchinsky all of whom are members of the Lieberman laboratory. The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries ? Tomorrow’s Cures. On the Web at www.wistar.org Contact: Greg Lester |
| Key to burning fat faster discovered Posted: 21 Aug 2012 09:00 PM PDT Enzymes involved in breaking down fat can now be manipulated to work three times harder by turning on a molecular switch recently observed by chemists at the University of Copenhagen. Being able to control this chemical on/off button could have massive implications for curing diseases related to obesity including diabetes, cardio vascular disease, stroke and even skin problems like acne. But the implications may be wider.
The results suggest that the switch may be a common characteristic of many more enzymes. Since enzymes are miniscule worker-molecules that control a vast variety of functions in cells, if the switches are standard, it may well be one of the most important discoveries in enzymology. “If many enzymes turn out to be switched on in the same way as the ones we’ve studied, this opens a door to understanding- and maybe curing, a wide range of diseases”, says professor Dimitrios Stamou. Stamou heads a multidisciplinary team of scientists at the Nanoscience Center and Department of Chemistry at the University of Copenhagen who published their discovery in the prominent scientific journal “Journal of the American Chemical Society“. Switch contradicts previous understanding
The discovery of the enzymatic ignition key contradicts previous ideas of how cells control the function of enzymes such as the fat eating lipase used in the current study. Researchers used to think that these enzymes work continuously at varying levels of efficiency. But in fact they are quite lazy. Very much like construction workers they work at a fixed efficiency for a given amount of time (working hours), and then they rest. And that’s good news for enzyme designers. Tripping their newfound switch resulted in tripling the working hours of lipase enzymes, from 15 percent of the time to 45 percent by the Copenhagen team Function follows form
In enzymes, function is decided by the shape of the molecule. So making them more efficient would have required a major reconstruction. In some cases so difficult that it is on the order of transforming a handsaw into a chainsaw, says the chemist, Assistant Professor Nikos Hatzakis, who was deeply involved in the scrutiny of the enzymes. “Changing the fundamental shape of a tool is always difficult. Whether it’s saw or an enzyme. But working longer hours with the same tool is infinitely easier. What we’ve achieved, is to make enzymes work longer hours”, explains Hatzakis. Scrutiny on the Nanoscale
Observing that enzymes even have an on-off switch may sound easy, but first the Bio Nano- team had to devise a way to study individual enzyme molecules. These are so small, that there are trillions in just a drop of water. So measuring the work of only one enzyme could be compared to looking down from the moon to detect each time a carpenter in a building in Copenhagen swings his hammer. Light emitting fat
To perform their studies the researchers chose a fat degrading lipase enzyme model system in collaboration with Danish industrial enzyme producer Novozymes. They used “fat” that would emit light each time the enzyme took a bite. This way they could monitor each and every catalytic cycle or single movement of work. To ensure realism the enzymes were placed on an artificial cell wall. An “in vivo like membrane system”, says Stamou. “Natural enzymes live in cells. Looking at them in a non native environment, would tell us as much as looking at a carpenter working in outer space wearing a space suit would tell us about builders”, explains Dimitrios Stamou and concludes: “Now that we have understood how to switch enzymes on and off we could use this knowledge in the future both for curing diseases but also to design novel enzymes for industrial applications”. Contact: Jes Andersen |
| You are subscribed to email updates from BreakThrough Digest Medical News To stop receiving these emails, you may unsubscribe now. | Email delivery powered by Google |
| Google Inc., 20 West Kinzie, Chicago IL USA 60610 | |
