Tag Archives: University of Georgia

The secret lives of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas (CRISPR-associated) proteins

This research isn’t quite as exciting as the title promises but it is important as it attempts to answer some fundamental questions about Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-Associated (Cas).proteins. From a June 13, 2018 news item on phys.org,

Recently published research from the University of Georgia and UConn Health [University of Connecticu Health Center] provides new insight about the basic biological mechanisms of the RNA-based viral immune system known as CRISPR-Cas.

CRISPR-Cas, short for Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated, is a defense mechanism that has evolved in bacteria and archaea that these single celled organisms use to ward off attacks from viruses and other invaders. When a bacterium is attacked by a virus, it makes a record of the virus’s DNA by chopping it up into pieces and incorporating a small segment of the invader’s DNA into its own genome. It then uses this DNA to make RNAs that bind with a bacterial protein that then kills the viral DNA.

The system has been studied worldwide in hopes that it can be used to edit genes that predispose humans to countless diseases, such as diabetes and cancer. However, to reach this end goal, scientists must gain further understanding of the basic biological process that leads to successful immunity against the invading virus.

A June 12, 2018 University of Georgia news release by Jessica Luton and Jessica McBride, which originated the news item, provides more detail,

Distinguished Research Professor of Biochemistry and Molecular Biology in UGA’s Franklin College of Arts and Sciences and principal investigator for the project Michael Terns and UGA postdoctoral fellow Masami Shiimori collaborated with Brenton Graveley and Sandra Garrett at UConn Health to sequence millions of genomes to learn more about the process. Graveley is professor and chair of the Department of Genetics and Genome Sciences and associate director of the Institute for Systems Genomics at UConn Health, and Garrett is a postdoctoral fellow in his laboratory.

“This research is more fundamental and basic than studies that are trying to determine how to use CRISPR for therapeutic or biomedical application,” said Terns. “Our study is about the unique first step in the process, known as adaptation, where fragments of DNA are recognized and integrated into the host genome and provide immunity for future generations.”

Previously, researchers did not understand how the cell recognized the virus as an invader, nor which bacterial proteins were necessary for successful integration and immunity.

“In this project we were able to determine how the bacterial immune system creates a molecular memory to remove harmful viral DNA sequences and how this is passed down to the bacterial progeny,” said Graveley.

By looking at patterns in the data, the researchers discovered several new findings about how two previously poorly characterized Cas4 proteins function in tandem with Cas1 and Cas2 proteins found in all CRISPR-Cas systems.

In this initial adaptation phase, one of two different Cas4 proteins recognizes a signaling placeholder in the sequence that occurs adjacent to the snippet of DNA that is excised.

When the Cas1 and Cas2 proteins are present in the cell with either of two Cas4 protein nucleases, Cas4-1 and Cas4-2, they act like the generals of this army-based immune system, communicating uniform sized clipped DNA fragments, directions on where to go next and ultimately instructions that destroy the lethal DNA fragment.

In order for a cell to successfully recognize and excise strands of DNA, incorporate them into its own genome and achieve immunity, the Cas4 proteins must be present in conjunction with the Cas1 and Cas2 proteins.

“Cas4 is present in many CRISPR-Cas systems, but the roles of the proteins were mysterious,” said Terns. “In our system, there are two Cas4 proteins that are essential for governing this process so that functional RNAs are made and immunity is conferred”

To achieve these findings, the research team from the University of Georgia created strains of archaeal organisms with key genetic deletions.

Hundreds of millions of DNA fragments captured in the CRISPR loci were sent to the Graveley lab in Farmington, Connecticut, where they were sequenced with the Illumina MiSeq system. The researchers then used supercomputing for bioinformatics analysis and data interpretation.

While there is still much to learn about the biological mechanisms involved in CRISPR-Cas systems, this research tells scientists more about the way these proteins work together to save the cell and achieve immunity.

“The data are so clear. We sequenced millions and millions of DNA fragments captured in CRISPR loci in different genetic strains and found the same results consistently,” he said.

Here’s a link to and a citation for the paper,

Cas4 Nucleases Define the PAM, Length, and Orientation of DNA Fragments Integrated at CRISPR Loci by Masami Shiimori, Sandra C. Garrett, Brenton R. Graveley, Michael P. Terns.Molecular Cell Volume 70, Issue 5, p814–824.e6, 7 June 2018 DOI: https://doi.org/10.1016/j.molcel.2018.05.002

This paper is behind a paywall.

Making magnetic rust behave like gold and the nanoscale

Researchers at the University of Georgia (US) have found a way to combine gold nanoparticles with magnetic rust nanoparticles for a hybrid structure that behaves with the properties of both types of nanoparticles. From a Sept. 15, 2016 news item on ScienceDaily,

Researchers from the University of Georgia are giving new meaning to the phrase “turning rust into gold”—and making the use of gold in research settings and industrial applications far more affordable.

The research is akin to a type of modern-day alchemy, said Simona Hunyadi Murph, adjunct professor in the UGA Franklin College of Arts and Sciences department of physics and astronomy. Researchers combine small amounts of gold nanoparticles with magnetic rust nanoparticles to create a hybrid nanostructure that retains both the properties of gold and rust.

A Sept. 15, 2016 University of Georgia news release by Jessica Luton, which originated the news item, expands on the theme,

“Medieval alchemists tried to create gold from other metals,” she said. “That’s kind of what we did with our research. It’s not real alchemy, in the medieval sense, but it is a sort of 21st century version.”

Gold has long been a valuable resource for industry, medicine, dentistry, computers, electronics and aerospace, among others, due to unique physical and chemical properties that make it inert and resistant to oxidation. But because of its high cost and limited supply, large scale projects using gold can be prohibitive. At the nanoscale, however, using a very small amount of gold is far more affordable.

In the new study published this summer in the Journal of Physical Chemistry C, the researchers used solution chemistry to reduce gold ions into a metallic gold structure using sodium citrate. In this process, if other ingredients-rust in this case-are present in the reaction pot during the transformation process, the metallic gold structures nucleate and grow on these “ingredients,” otherwise known as supports.

“We are really excited to share our new discoveries. When researchers are looking at gold as a potential material for research, we talk about how expensive gold is. For the first time ever, we’ve been able to create a new class of cheaper, highly efficient, nontoxic, magnetically reusable hybrid nanomaterials that contain a far more abundant material-rust-than the typical noble metal gold,” said Murph, who is also a principal scientist in the National Security Directorate at the Savannah River National Laboratory in Aiken, South Carolina.

When materials are broken down in size to reach nanometer scale dimensions-1-100 nanometers, which is approximately 100,000 times smaller than the diameter of human hair-these substances can take on new properties. For example, bulk gold does not display catalytic properties; however, at the nanoscale, gold is an efficient catalyst, accelerating chemical change for many reactions including oxidation, hydrogen production or reduction of aromatic nitro compounds.

Gold nanoparticles of different sizes and shapes display different colors when impinged by light because they absorb and scatter light at specific wavelengths, known as plasmonic resonances. These plasmonic resonances are of particular interest for biological applications. If someone shines light on the gold nanoparticles, the absorbed light can be converted to heat in the surrounding media, and if bacteria or cancerous cells are in the vicinity of such gold nanoparticles, they can be destroyed by using light of appropriate wavelength. This phenomenon is known as photothermal therapy.

By replacing some of the nano-gold with magnetic nano-rust, researchers show that the hybrid gold and rust nanostructures are able to photothermally heat the surrounding media as efficiently as pure gold nanoparticles, even with a significantly smaller concentration of gold.

“In a way, we’ve done a little better than alchemy,” said George Larsen, co-investigator and postdoctoral researcher in the Group for Innovation and Advancements in Nano-Technology Sciences at the Savannah River National Laboratory, “because these new hybrid nanoparticles not only behave better than gold in some cases, but also have magnetic functionality.”

Murph and her team looked at three different shapes of hybrid nanoparticles in this research-spheres, rings and tubes.

“A differently shaped nanoparticle means that the atoms are arranged differently-into cubes, hexagons or triangles, for example,” she said. “A different atom arrangement means different packing densities, spacing between atoms, defects, surface area and surface energies. Different shapes lead to an increased atom area that is exposed to catalyze a chemical reaction. Scientifically speaking, different shape means different crystallographic facets and surface energy that could lead to higher catalytic activity and different catalytic products.

“The results of our research showed that the ring- and tube-shaped hybrid nanoparticles proved to be better catalytic materials than the sphere-shaped nanoparticles because of the way the atoms are arranged in the structure at this nanoscale. More importantly, the hybrid nanoparticles of gold and rust are better catalysts than gold nanoparticles alone, even with a significantly smaller amount of gold.

When these different shaped hybrid nanoparticles were exposed to light of specific wavelength, the spheres heated the solution up to slightly higher temperatures than the ring- or tube-shaped nanoparticles.

“This could have a variety of biological applications such as tracking, drug delivery or imaging inside the body,” Murph said. “If you feed these gold nanoparticles to bacteria and shine the light on them, you could destroy these by just using light.”

The hybrid structures could also be used for new application [sic], such as sensing, hyperthermia treatment, environmental cleaning and protection medical imaging applications including magnetic resonance imaging contrast agents, product detection and manipulation.

Here’s a link to and a citation for the paper/video,

Multifunctional Hybrid Fe2O3-Au Nanoparticles for Efficient Plasmonic Heating by Simona E. Hunyadi Murph, George K. Larsen, Robert J. Lascola. Journal of Visualized Experiments, 2016; (108) DOI: 10.3791/53598

This paper/video appears to be open access.

Unleashing graphene electronics potential with a trio of 2D nanomaterials

Graphene has excited a great deal of interest, especially with regard to its application in the field of electronics. However, it seems that graphene may need a little help from its friends, tantalum sulfide and boron nitride, according to a July 6, 2016 news item on ScienceDaily,

Graphene has emerged as one of the most promising two-dimensional crystals, but the future of electronics may include two other nanomaterials, according to a new study by researchers at the University of California, Riverside and the University of Georgia.

In research published Monday (July 4 [2016]) in the journal Nature Nanotechnology, the researchers described the integration of three very different two-dimensional (2D) materials to yield a simple, compact, and fast voltage-controlled oscillator (VCO) device. A VCO is an electronic oscillator whose oscillation frequency is controlled by a voltage input.

Titled “An integrated Tantalum Sulfide–Boron Nitride–Graphene Oscillator: A Charge-Density-Wave Device Operating at Room Temperature,” the paper describes the development of the first useful device that exploits the potential of charge-density waves to modulate an electrical current through a 2D material. The new technology could become an ultralow power alternative to conventional silicon-based devices, which are used in thousands of applications from computers to clocks to radios. The thin, flexible nature of the device would make it ideal for use in wearable technologies.

A July 5, 2016 University of California at Riverside (UCR) news release (also on EurekAlert) by Sarah Nightingale, which originated the news item, expands on the theme,

Graphene, a single layer of carbon atoms that exhibits exceptional electrical and thermal conductivities, shows promise as a successor to silicon-based transistors. However, its application has been limited by its inability to function as a semiconductor, which is critical for the ‘on-off’ switching operations performed by electronic components.

To overcome this shortfall, the researchers turned to another 2D nanomaterial, Tantalum Sulfide (TaS2). They showed that voltage-induced changes in the atomic structure of the ‘1T prototype’ of TaS2 enable it to function as an electrical switch at room temperature–a requirement for practical applications.

“There are many charge-density wave materials that have interesting electrical switching properties. However, most of them reveal these properties at very low temperature only. The particular polytype of TaS2 that we used can have abrupt changes in resistance above room temperature. That made a crucial difference,” said Alexander Balandin, UC presidential chair professor of electrical and computer engineering in UCR’s Bourns College of Engineering, who led the research team.

To protect the TaS2 from environmental damage, the researchers coated it with another 2D material, hexagonal boron nitrate, to prevent oxidation. By pairing the boron nitride-capped TaS2 with graphene, the team constructed a three-layer VCO that could pave the way for post-silicon electronics. In the proposed design, graphene functions as an integrated tunable load resistor, which enables precise voltage control of the current and VCO frequency. The prototype UCR devices operated at MHz frequency used in radios, and the extremely fast physical processes that define the device functionality allow for the operation frequency to increase all the way to THz.

Balandin said the integrated system is the first example of a functional voltage-controlled oscillator device comprising 2D materials that operates at room temperature.

“It is difficult to compete with silicon, which has been used and improved for the past 50 years. However, we believe our device shows a unique integration of three very different 2D materials, which utilizes the intrinsic properties of each of these materials. The device can potentially become a low-power alternative to conventional silicon technologies in many different applications,” Balandin said.

The electronic function of graphene envisioned in the proposed 2D device overcomes the problem associated with the absence of the energy band gap, which so far prevented graphene’s use as the transistor channel material. The extremely high thermal conductivity of graphene comes as an additional benefit in the device structure, by facilitating heat removal. The unique heat conduction properties of graphene were experimentally discovered and theoretically explained in 2008 by Balandin’s group at UCR. The Materials Research Society recognized this groundbreaking achievement by awarding Balandin the MRS Medal in 2013.

The Balandin group also demonstrated the first integrated graphene heat spreaders for high-power transistors and light-emitting diodes. “In those applications, graphene was used exclusively as heat conducting material. Its thermal conductivity was the main property. In the present device, we utilize both electrical and thermal conductivity of graphene,” Balandin added.

Here’s a link to and a citation for the paper,

A charge-density-wave oscillator based on an integrated tantalum disulfide–boron nitride–graphene device operating at room temperature by Guanxiong Liu, Bishwajit Debnath, Timothy R. Pope, Tina T. Salguero, Roger K. Lake, & Alexander A. Balandin. Nature Nanotechnology (2016) doi:10.1038/nnano.2016.108 Published online 04 July 2016

This paper is behind a paywall.

The world’s smallest diode is made from a single molecule

Both the University of Georgia (US) and the American Associates Ben-Gurion University of the Negev (Israel) have issued press releases about a joint research project resulting in the world’s smallest diode.

I stumbled across the April 4, 2016 University of Georgia news release on EurekAlert first,

Researchers at the University of Georgia and at Ben-Gurion University in Israel have demonstrated for the first time that nanoscale electronic components can be made from single DNA molecules. Their study, published in the journal Nature Chemistry, represents a promising advance in the search for a replacement for the silicon chip.

The finding may eventually lead to smaller, more powerful and more advanced electronic devices, according to the study’s lead author, Bingqian Xu.

“For 50 years, we have been able to place more and more computing power onto smaller and smaller chips, but we are now pushing the physical limits of silicon,” said Xu, an associate professor in the UGA College of Engineering and an adjunct professor in chemistry and physics. “If silicon-based chips become much smaller, their performance will become unstable and unpredictable.”

To find a solution to this challenge, Xu turned to DNA. He says DNA’s predictability, diversity and programmability make it a leading candidate for the design of functional electronic devices using single molecules.

In the Nature Chemistry paper, Xu and collaborators at Ben-Gurion University of the Negev describe using a single molecule of DNA to create the world’s smallest diode. A diode is a component vital to electronic devices that allows current to flow in one direction but prevents its flow in the other direction.

Xu and a team of graduate research assistants at UGA isolated a specifically designed single duplex DNA of 11 base pairs and connected it to an electronic circuit only a few nanometers in size. After the measured current showed no special behavior, the team site-specifically intercalated a small molecule named coralyne into the DNA. They found the current flowing through the DNA was 15 times stronger for negative voltages than for positive voltages, a necessary feature of a diode.

“This finding is quite counterintuitive because the molecular structure is still seemingly symmetrical after coralyne intercalation,” Xu said.

A theoretical model developed by Yanantan Dubi of Ben-Gurion University indicated the diode-like behavior of DNA originates from the bias voltage-induced breaking of spatial symmetry inside the DNA molecule after the coralyne is inserted.

“Our discovery can lead to progress in the design and construction of nanoscale electronic elements that are at least 1,000 times smaller than current components,” Xu said.

The research team plans to continue its work, with the goal of constructing additional molecular devices and enhancing the performance of the molecular diode.

The April 4, 2016 American Associates Ben-Gurion University of the Negev press release on EurekAlert covers much of the same ground while providing some new details,

The world’s smallest diode, the size of a single molecule, has been developed collaboratively by U.S. and Israeli researchers from the University of Georgia and Ben-Gurion University of the Negev (BGU).

“Creating and characterizing the world’s smallest diode is a significant milestone in the development of molecular electronic devices,” explains Dr. Yoni Dubi, a researcher in the BGU Department of Chemistry and Ilse Katz Institute for Nanoscale Science and Technology. “It gives us new insights into the electronic transport mechanism.”

Continuous demand for more computing power is pushing the limitations of present day methods. This need is driving researchers to look for molecules with interesting properties and find ways to establish reliable contacts between molecular components and bulk materials in an electrode, in order to mimic conventional electronic elements at the molecular scale.

An example for such an element is the nanoscale diode (or molecular rectifier), which operates like a valve to facilitate electronic current flow in one direction. A collection of these nanoscale diodes, or molecules, has properties that resemble traditional electronic components such as a wire, transistor or rectifier. The emerging field of single molecule electronics may provide a way to overcome Moore’s Law– the observation that over the history of computing hardware the number of transistors in a dense integrated circuit has doubled approximately every two years – beyond the limits of conventional silicon integrated circuits.

Prof. Bingqian Xu’s group at the College of Engineering at the University of Georgia took a single DNA molecule constructed from 11 base pairs and connected it to an electronic circuit only a few nanometers in size. When they measured the current through the molecule, it did not show any special behavior. However, when layers of a molecule called “coralyne,” were inserted (or intercalated) between layers of DNA, the behavior of the circuit changed drastically. The current jumped to 15 times larger negative vs. positive voltages–a necessary feature for a nano diode. “In summary, we have constructed a molecular rectifier by intercalating specific, small molecules into designed DNA strands,” explains Prof. Xu.

Dr. Dubi and his student, Elinor Zerah-Harush, constructed a theoretical model of the DNA molecule inside the electric circuit to better understand the results of the experiment. “The model allowed us to identify the source of the diode-like feature, which originates from breaking spatial symmetry inside the DNA molecule after coralyne is inserted.”

There’s an April 4, 2016 posting on the Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website) which provides a brief overview and a link to a previous essay, Whatever Happened to the Molecular Computer?

Here’s a link and citation for the paper,

Molecular rectifier composed of DNA with high rectification ratio enabled by intercalation by Cunlan Guo, Kun Wang, Elinor Zerah-Harush, Joseph Hamill, Bin Wang, Yonatan Dubi, & Bingqian Xu. Nature Chemistry (2016) doi:10.1038/nchem.2480 Published online 04 April 2016

This paper is behind a paywall.

$5.2M in nanotechnology grants from the US Department of Agriculture (USDA)

A March 30, 2016 news item on Nanowerk announces the 2016 nanotechnology grants from the US Dept. of Agriculture (USDA),

Agriculture Secretary Tom Vilsack today [March 30, 2016] announced an investment of more than $5.2 million to support nanotechnology research at 11 universities. The universities will research ways nanotechnology can be used to improve food safety, enhance renewable fuels, increase crop yields, manage agricultural pests, and more. The awards were made through the Agriculture and Food Research Initiative (AFRI), the nation’s premier competitive, peer-reviewed grants program for fundamental and applied agricultural sciences.

A March 30, 2016 USDA news release provides more detail,

“In the seven years since the Agriculture and Food Research Initiative was established, the program has led to true innovations and ground-breaking discoveries in agriculture to combat childhood obesity, improve and sustain rural economic growth, address water availability issues, increase food production, find new sources of energy, mitigate the impacts of climate variability and enhance resiliency of our food systems, and ensure food safety. Nanoscale science, engineering, and technology are key pieces of our investment in innovation to ensure an adequate and safe food supply for a growing global population,” said Vilsack. “The President’s 2017 Budget calls for full funding of the Agriculture and Food Research Initiative so that USDA can continue to support important projects like these.”

Universities receiving funding include Auburn University in Auburn, Ala.; Connecticut Agricultural Experiment Station in New Haven, Conn.; University of Central Florida in Orlando, Fla; University of Georgia in Athens, Ga.; Iowa State University in Ames, Iowa; University of Massachusetts in Amherst, Mass.; Mississippi State University in Starkville, Miss.; Lincoln University in Jefferson City, Mo.; Clemson University in Clemson, S.C.; Virginia Polytechnic Institute and State University in Blacksburg, Va.; and University of Wisconsin in Madison, Wis.

With this funding, Auburn University proposes to improve pathogen monitoring throughout the food supply chain by creating a user-friendly system that can detect multiple foodborne pathogens simultaneously, accurately, cost effectively, and rapidly. Mississippi State University will research ways nanochitosan can be used as a combined fire-retardant and antifungal wood treatment that is also environmentally safe. Experts in nanotechnology, molecular biology, vaccines and poultry diseases at the University of Wisconsin will work to develop nanoparticle-based poultry vaccines to prevent emerging poultry infections. USDA has a full list of projects and longer descriptions available online.

Past projects include a University of Georgia project developing a bio-nanocomposites-based, disease-specific, electrochemical sensors for detecting fungal pathogen induced volatiles in selected crops; and a University of Massachusetts project creating a platform for pathogen detection in foods that is superior to the current detection method in terms of analytical time, sensitivity, and accuracy using a novel, label-free, surface-enhanced Raman scattering (SERS) mapping technique.

The purpose of AFRI is to support research, education, and extension work by awarding grants that address key problems of national, regional, and multi-state importance in sustaining all components of food and agriculture. AFRI is the flagship competitive grant program administered by USDA’s National Institute of Food and Agriculture [NIFA]. Established under the 2008 Farm Bill, AFRI supports work in six priority areas: plant health and production and plant products; animal health and production and animal products; food safety, nutrition and health; bioenergy, natural resources and environment; agriculture systems and technology; and agriculture economics and rural communities. Since AFRI’s creation, NIFA has awarded more than $89 million to solve challenges related to plant health and production; $22 million of this has been dedicated to nanotechnology research. The President’s 2017 budget request proposes to fully fund AFRI for $700 million; this amount is the full funding level authorized by Congress when it established AFRI in the 2008 Farm Bill.

Each day, the work of USDA scientists and researchers touches the lives of all Americans: from the farm field to the kitchen table and from the air we breathe to the energy that powers our country. USDA science is on the cutting edge, helping to protect, secure, and improve our food, agricultural and natural resources systems. USDA research develops and transfers solutions to agricultural problems, supporting America’s farmers and ranchers in their work to produce a safe and abundant food supply for more than 100 years. This work has helped feed the nation and sustain an agricultural trade surplus since the 1960s. Since 2009, USDA has invested $4.32 billion in research and development grants. Studies have shown that every dollar invested in agricultural research now returns over $20 to our economy.

Since 2009, NIFA has invested in and advanced innovative and transformative initiatives to solve societal challenges and ensure the long-term viability of agriculture. NIFA’s integrated research, education, and extension programs, supporting the best and brightest scientists and extension personnel, have resulted in user-inspired, groundbreaking discoveries that are combating childhood obesity, improving and sustaining rural economic growth, addressing water availability issues, increasing food production, finding new sources of energy, mitigating climate variability, and ensuring food safety.

Imaging and treating artherosclerosis with a nanoparticle

For anyone concerned about atherosclerosis (build up of plaque in the arteries) and who doesn’t need immediate assistance, this is encouraging news. A March 14, 2016 news item on ScienceDaily announces research into a nanoparticle that could both image and treat the condition,

Atherosclerosis, a disease in which plaque builds up inside arteries, is a prolific and invisible killer, but it may soon lose its ability to hide in the body and wreak havoc. Scientists have now developed a nanoparticle that functionally mimics nature’s own high-density lipoprotein (HDL). The nanoparticle can simultaneously light up and treat atherosclerotic plaques that clog arteries. Therapy with this approach could someday help prevent deadly heart attacks and strokes.

A March 13, 2016 American Chemical Society (ACS) news release (also on EurekAlert), which originated the news item, expands on the theme,

The researchers present their work today [March 13, 2016] at the 251st National Meeting & Exposition of the American Chemical Society (ACS). …

“Other researchers have shown that if you isolate HDL components from donated blood, reconstitute them and inject them into animals, there seems to be a therapeutic effect,” says Shanta Dhar, Ph.D. “However, with donors’ blood, there is the chance of immunological rejection. This technology also suffers scale-up challenges. Our motivation was to avoid immunogenic factors by making a synthetic nanoparticle which can functionally mimic HDL. At the same time, we wanted a way to locate the synthetic particles.”

Current detection strategies often fail to identify dangerous plaques, which can clog arteries over time or break off from arterial walls and block blood flow, causing a heart attack or stroke. Magnetic resonance imaging (MRI) offers a potential approach for plaque visualization, but requires the use of a contrast agent to show the atherosclerotic plaques clearly. But the potential for harmful immune reactions still exists with the use of donor-derived HDL.

Beyond imaging, there is a therapeutic aspect of using HDL. HDL is widely known as “good” cholesterol because of its ability to pull low-density lipoprotein, or “bad” cholesterol, out of plaques. This process shrinks the plaques, making them less likely to clog arteries or break apart.

To simultaneously identify and treat atherosclerosis without triggering an immune response, Dhar and Bhabatosh Banik, Ph.D., a postdoctoral fellow in her lab, created an MRI-active HDL mimic. The researchers, who are at the University of Georgia, Athens, had previously built synthetic HDL particles lacking a contrast agent. These particles lowered levels of total cholesterol and triglycerides in mice.

“The key challenge, then, was designing the contrast agent,” Banik says. “It took time to figure out the optimal lipophilicity and solubility.” The contrast agent, iron oxide, needs to be encapsulated in the synthetic lipoparticle’s hydrophobic core to provide the brightest possible signal. Eventually, the researchers hit on the right chemical combination — iron oxide with a fatty surface coating — for optimal particle encapsulation. They successfully visualized the contrast agent using MRI in cell studies.

The researchers are applying their synthetic nanoparticle to distinguish between unstable plaques and stationary ones. To do this, Dhar targeted the new MRI-active HDL mimics to macrophages, which are white blood cells that, along with lipids and cholesterol, make up atherosclerotic plaques.

The researchers targeted macrophages by decorating the nanoparticles’ surfaces with a molecule that selectively binds to macrophages. The team observed that the nanoparticles were engulfed by these white blood cells. “Then, when the macrophages ruptured, which is a sign of an unstable plaque, the cells spit out the nanoparticles, causing the MRI signal to change in a detectable fashion,” Banik says.

Dhar says her lab is now using MRI to study how well the particles light up and treat plaques in animals, and she hopes to begin clinical trials within two years. [emphasis mine]

Good luck to the researchers!

Brushing your way to nanofibres

The scientists are using what looks like a hairbrush to create nanofibres ,

Figure 2: Brush-spinning of nanofibers. (Reprinted with permission by Wiley-VCH Verlag)) [downloaded from http://www.nanowerk.com/spotlight/spotid=41398.php]

Figure 2: Brush-spinning of nanofibers. (Reprinted with permission by Wiley-VCH Verlag)) [downloaded from http://www.nanowerk.com/spotlight/spotid=41398.php]

A Sept. 23, 2015 Nanowerk Spotlight article by Michael Berger provides an in depth look at this technique (developed by a joint research team of scientists from the University of Georgia, Princeton University, and Oxford University) which could make producing nanofibers for use in scaffolds (tissue engineering and other applications) more easily and cheaply,

Polymer nanofibers are used in a wide range of applications such as the design of new composite materials, the fabrication of nanostructured biomimetic scaffolds for artificial bones and organs, biosensors, fuel cells or water purification systems.

“The simplest method of nanofiber fabrication is direct drawing from a polymer solution using a glass micropipette,” Alexander Tokarev, Ph.D., a Research Associate in the Nanostructured Materials Laboratory at the University of Georgia, tells Nanowerk. “This method however does not scale up and thus did not find practical applications. In our new work, we introduce a scalable method of nanofiber spinning named touch-spinning.”

James Cook in a Sept. 23, 2015 article for Materials Views provides a description of the technology,

A glass rod is glued to a rotating stage, whose diameter can be chosen over a wide range of a few centimeters to more than 1 m. A polymer solution is supplied, for example, from a needle of a syringe pump that faces the glass rod. The distance between the droplet of polymer solution and the tip of the glass rod is adjusted so that the glass rod contacts the polymer droplet as it rotates.

Following the initial “touch”, the polymer droplet forms a liquid bridge. As the stage rotates the bridge stretches and fiber length increases, with the diameter decreasing due to mass conservation. It was shown that the diameter of the fiber can be precisely controlled down to 40 nm by the speed of the stage rotation.

The method can be easily scaled-up by using a round hairbrush composed of 600 filaments.

When the rotating brush touches the surface of a polymer solution, the brush filaments draw many fibers simultaneously producing hundred kilometers of fibers in minutes.

The drawn fibers are uniform since the fiber diameter depends on only two parameters: polymer concentration and speed of drawing.

Returning to Berger’s Spotlight article, there is an important benefit with this technique,

As the team points out, one important aspect of the method is the drawing of single filament fibers.

These single filament fibers can be easily wound onto spools of different shapes and dimensions so that well aligned one-directional, orthogonal or randomly oriented fiber meshes with a well-controlled average mesh size can be fabricated using this very simple method.

“Owing to simplicity of the method, our set-up could be used in any biomedical lab and facility,” notes Tokarev. “For example, a customized scaffold by size, dimensions and othermorphologic characteristics can be fabricated using donor biomaterials.”

Berger’s and Cook’s articles offer more illustrations and details.

Here’s a link to and a citation for the paper,

Touch- and Brush-Spinning of Nanofibers by Alexander Tokarev, Darya Asheghal, Ian M. Griffiths, Oleksandr Trotsenko, Alexey Gruzd, Xin Lin, Howard A. Stone, and Sergiy Minko. Advanced Materials DOI: 10.1002/adma.201502768ViewFirst published: 23 September 2015

This paper is behind a paywall.

Brain-friendly interface to replace neural prosthetics one day?

This research will not find itself occupying anyone’s brain for some time to come but it is interesting to find out that neural prosthetics have some drawbacks and there is work being done to address them. From an Aug. 10, 2015 news item on Azonano,

Instead of using neural prosthetic devices–which suffer from immune-system rejection and are believed to fail due to a material and mechanical mismatch–a multi-institutional team, including Lohitash Karumbaiah of the University of Georgia’s Regenerative Bioscience Center, has developed a brain-friendly extracellular matrix environment of neuronal cells that contain very little foreign material. These by-design electrodes are shielded by a covering that the brain recognizes as part of its own composition.

An Aug. 5, 2015 University of Georgia news release, which originated the news item, describes the new approach and technique in more detail,

Although once believed to be devoid of immune cells and therefore of immune responses, the brain is now recognized to have its own immune system that protects it against foreign invaders.

“This is not by any means the device that you’re going to implant into a patient,” said Karumbaiah, an assistant professor of animal and dairy science in the UGA College of Agricultural and Environmental Sciences. “This is proof of concept that extracellular matrix can be used to ensheathe a functioning electrode without the use of any other foreign or synthetic materials.”

Implantable neural prosthetic devices in the brain have been around for almost two decades, helping people living with limb loss and spinal cord injury become more independent. However, not only do neural prosthetic devices suffer from immune-system rejection, but most are believed to eventually fail because of a mismatch between the soft brain tissue and the rigid devices.

The collaboration, led by Wen Shen and Mark Allen of the University of Pennsylvania, found that the extracellular matrix derived electrodes adapted to the mechanical properties of brain tissue and were capable of acquiring neural recordings from the brain cortex.

“Neural interface technology is literally mind boggling, considering that one might someday control a prosthetic limb with one’s own thoughts,” Karumbaiah said.

The study’s joint collaborators were Ravi Bellamkonda, who conceived the new approach and is chair of the Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University, as well as Allen, who at the time was director of the Institute for Electronics and Nanotechnology.

“Hopefully, once we converge upon the nanofabrication techniques that would enable these to be clinically translational, this same methodology could then be applied in getting these extracellular matrix derived electrodes to be the next wave of brain implants,” Karumbaiah said.

Currently, one out of every 190 Americans is living with limb loss, according to the National Institutes of Health. There is a significant burden in cost of care and quality of life for people suffering from this disability.

The research team is one part of many in the prosthesis industry, which includes those who design the robotics for the artificial limbs, others who make the neural prosthetic devices and developers who design the software that decodes the neural signal.

“What neural prosthetic devices do is communicate seamlessly to an external prosthesis,” Karumbaiah said, “providing independence of function without having to have a person or a facility dedicated to their care.”

Karumbaiah hopes further collaboration will allow them to make positive changes in the industry, saying that, “it’s the researcher-to-industry kind of conversation that now needs to take place, where companies need to come in and ask: ‘What have you learned? How are the devices deficient, and how can we make them better?'”

Here’s a link to and a citation for the paper,

Extracellular matrix-based intracortical microelectrodes: Toward a microfabricated neural interface based on natural materials by Wen Shen, Lohitash Karumbaiah, Xi Liu, Tarun Saxena, Shuodan Chen, Radhika Patkar, Ravi V. Bellamkonda, & Mark G. Allen. Microsystems & Nanoengineering 1, Article number: 15010 (2015) doi:10.1038/micronano.2015.10

This appears to be an open access paper.

One final note, I have written frequently about prosthetics and neural prosthetics, which you can find by using either of those terms and/or human enhancement. Here’s my latest piece, a March 25, 2015 posting.

Magnetospinning with an inexpensive magnet

The fridge magnet mentioned in the headline for a May 11, 2015  Nanowerk spotlight aricle by Michael Berger isn’t followed up until the penultimate paragraph but it is worth the wait,

“Our method for spinning of continuous micro- and nanofibers uses a permanent revolving magnet,” Alexander Tokarev, Ph.D., a Research Associate in the Nanostructured Materials Laboratory at the University of Georgia, tells Nanowerk. “This fabrication technique utilizes magnetic forces and hydrodynamic features of stretched threads to produce fine nanofibers.”

“The new method provides excellent control over the fiber diameter and is compatible with a range of polymeric materials and polymer composite materials including biopolymers,” notes Tokarev. “Our research showcases this new technique and demonstrates its advantages to the scientific community.”

Electrospinning is the most popular method to produce nanofibers in labs now. Owing to its simplicity and low costs, a magnetospinning set-up could be installed in any non-specialized laboratory for broader use of magnetospun nanofibers in different methods and technologies. The total cost of a laboratory electrospinning system is above $10,000. In contrast, no special equipment is needed for magnetospinning. It is possible to build a magnetospinning set-up, such as the University of Georgia team utilizes, by just using a $30 rotating motor and a $5 permanent magnet. [emphasis mine]

Berger’s article references a recent paper published by the team,

Magnetospinning of Nano- and Microfibers by Alexander Tokarev, Oleksandr Trotsenko, Ian M. Griffiths, Howard A. Stone, and Sergiy Minko. Advanced Materials First published: 8 May 2015Full publication history DOI: 10.1002/adma.201500374View/save citation

This paper is behind a paywall.

* The headline originally stated that a ‘fridge’ magnet was used. Researcher Alexander Tokarev kindly dropped by correct this misunderstanding on my part and the headline has been changed to read  ‘inexpensive magnet’ on May 14, 2015 at approximately 1400 hundred hours PDT.

A labradoodle, gold nanoparticles, and cancer treatment for dogs and cats

Here’s the labradoodle,

Caption: Dr. Shawna Klahn, an assistant professor of oncology at the Virginia-Maryland College of Veterinary Medicine, performs a checkup on "Grayton" four weeks after the animal's experimental cancer treatment involving gold nanoparticles and a targeted laser therapy. Credit: Virginia Tech

Caption: Dr. Shawna Klahn, an assistant professor of oncology at the Virginia-Maryland College of Veterinary Medicine, performs a checkup on “Grayton” four weeks after the animal’s experimental cancer treatment involving gold nanoparticles and a targeted laser therapy.
Credit: Virginia Tech

An Aug. 6, 2014 news item on Azonano outlines ‘Grayton’s’ story and how gold nanoparticles will factor in,

When Michael and Sandra Friedlander first came to the Virginia-Maryland College of Veterinary Medicine three years ago with their dog, Grayton, they learned some bad news: Grayton had nasal adenocarcinoma, a form of cancer with a short life expectancy.

“Most dogs with this form of cancer are with their owners no more than a few months after the diagnosis, but here Grayton is three years later,” said Michael Friedlander, who is the executive director of the Virginia Tech Carilion Research Institute and senior dean at the Virginia Tech Carilion School of Medicine.

No stranger to medical research, Friedlander was referred by Veterinary Teaching Hospital clinicians to an experimental treatment at the University of Florida called stereotactic radiation therapy, which delivers precise, high dosages of radiation to a tumor and can only be performed once.

“That shrunk the tumor down to almost nothing,” said Friedlander, who is also the associate provost for health sciences at Virginia Tech. “We knew when Grayton had the procedure that we couldn’t do it again, but now the cancer is back.”

An Aug. 4, 2014 Virginia Tech news release (also on EurekAlert) by Michael Sutphin, which originated the news item, explains what occasioned the release and how gold nanoparticles are being used in veterinary treatment for cancer,

Today [Aug. 4, 2014], the 11-year-old Labradoodle is the first patient at the Virginia-Maryland College of Veterinary Medicine in a new clinical trial that is testing the use of gold nanoparticles and a targeted laser treatment for solid tumors in dogs and cats. The study is one of several on new treatments for client-owned companion animals at the college. In January [2014], the college established the Veterinary Clinical Research Office to help facilitate this work.

“Clinical research at the veterinary college involves both primary research focused on advancing the treatment and diagnosis of veterinary diseases and translational research in which spontaneous diseases in animals can be used as models of human disease,” said Dr. Greg Daniel, head of the Department of Small Animal Clinical Sciences. “In the latter situation, we can provide our companion animal patients with treatment and diagnostic options that are not yet available in mainstream human medicine.”

Although medical researchers have tested gold nanoparticles with targeted laser treatments on human patients with some success, the treatment is still new to both human and veterinary medicine. The college is one of four current veterinary schools around the country testing the AuroLase therapy developed by Nanospectra Biosciences Inc., a startup company based in Houston, Texas. The others are Texas A&M University, the University of Wisconsin-Madison, and the University of Georgia.

Dr. Nick Dervisis, assistant professor of oncology in the Department of Small Animal Clinical Sciences, is leading the Nanospectra-funded study. Following a rhinoscopy performed on Grayton by Dr. David Grant, associate professor of internal medicine, Dervisis began the one-time, experimental therapy.

“The treatment involves two phases,” Dervisis said. “First, we infuse the patient with the gold nanoparticles. Although the nanoparticles distribute throughout the body, they tend to concentrate around blood vessels associated with tumors. Within 36 hours, they have cleared the bloodstream except for tumors. The gold nanoparticles are small enough to circulate freely in the bloodstream and become temporarily captured within the incomplete blood vessel walls common in solid tumors. Then, we use a non-ablative laser on the patient.”

Dervisis explained that a non-ablative laser is not strong enough to harm the skin or normal tissue, but “it does cause the remaining nanoparticles to absorb the laser energy and convert it into heat so that they damage the tumor cells.”

Like all clinical trials, the study involves many unknowns, including the treatment’s usefulness and effectiveness. One month after the AuroLase treatment, the nosebleeds that initially brought Grayton back to the Veterinary Teaching Hospital had stopped and Grayton has no other side effects.

“I’m delighted with the care and service that Grayton has received at the veterinary college,” said Friedlander, who explained that the treatment appears to be safe even though researchers do not know whether it is effective yet. “Grayton recently came with us on our annual vacation at the beach. We didn’t know if he would be able to come again, so it was great to have him with us swimming, catching fish and crabs, and doing what dogs do.”

Current clinical trials at the veterinary college range from the use of MRI to distinguish between benign and cancerous lymph nodes in dogs with oral melanoma, to a new chemotherapy drug for dogs with brain tumors, to the treatment of invasive skin cancer in horses with high-voltage, high-frequency electrical pulses. A complete list of current trials can be found at the college’s new clinical trials website.

Mindy Quigley, who oversees the college’s Veterinary Clinical Research Office, explained that veterinary trials, which follow a four-phase process and a variety of regulations similar to human medicine, have another layer of complexity that human trials do not.

“Variation among species means that a therapy that has proven safe and effective in, for example, humans or dogs, may not work for horses,” said Quigley, who comes to the college from the University of Edinburgh’s College of Medicine and Veterinary Medicine, where she helped set up a new neurology research clinic with funding from author J.K. Rowling. “Many veterinary clinical trials must therefore take therapies that have worked in one species and test them in other species with similar conditions. This is a necessary step to determine if a proposed treatment is safe and effective for our companion animals.”

Grayton may be the first companion animal in the AuroLase study at the veterinary college, but he certainly won’t be the last. Dervisis is continuing to enroll patients in the study and is seeking dogs and cats of a certain size with solid tumors who have not recently received radiation therapy or chemotherapy.

Interested parties can check this site for current clinical trials, including the Aurolase study,  being held by the Virginia-Maryland Regional College of Veterinary Medicine.