Motorized prosthetic arm can sense touch, move with your thoughts

Keven Walgamott had a good "feeling" about picking up the egg without crushing it. What seems simple for nearly everyone else can be more of a Herculean task for Walgamott, who lost his left hand and part of his arm in an electrical accident 17 years ago. But he was testing out the prototype of a high-tech prosthetic arm with fingers that not only can move, they can move with his thoughts. And thanks to a biomedical engineering team at the University of Utah, he "felt" the egg well enough so his brain could tell the prosthetic hand not to squeeze too hard.

That's because the team, led by University of Utah biomedical engineering associate professor Gregory Clark, has developed a way for the "LUKE Arm" (so named after the robotic hand that Luke Skywalker got in "The Empire Strikes Back") to mimic the way a human hand feels objects by sending the appropriate signals to the brain. Their findings were published in a new paper co-authored by U biomedical engineering doctoral student Jacob George, former doctoral student David Kluger, Clark and other colleagues in the latest edition of the journal Science Robotics.
"We changed the way we are sending that information to the brain so that it matches the human body. And by matching the human body, we were able to see improved benefits," George says. "We're making more biologically realistic signals."
That means an amputee wearing the prosthetic arm can sense the touch of something soft or hard, understand better how to pick it up, and perform delicate tasks that would otherwise be impossible with a standard prosthetic with metal hooks or claws for hands.
"It almost put me to tears," Walgamott says about using the LUKE Arm for the first time during clinical tests in 2017. "It was really amazing. I never thought I would be able to feel in that hand again."
Walgamott, a real estate agent from West Valley City, Utah, and one of seven test subjects at the University of Utah, was able to pluck grapes without crushing them, pick up an egg without cracking it, and hold his wife's hand with a sensation in the fingers similar to that of an able-bodied person.
"One of the first things he wanted to do was put on his wedding ring. That's hard to do with one hand," says Clark. "It was very moving."
How those things are accomplished is through a complex series of mathematical calculations and modeling.
The LUKE Arm
The LUKE Arm has been in development for some 15 years. The arm itself is made of mostly metal motors and parts with a clear silicon "skin" over the hand. It is powered by an external battery and wired to a computer. It was developed by DEKA Research & Development Corp., a New Hampshire-based company founded by Segway inventor Dean Kamen.
Meanwhile, the University of Utah team has been developing a system that allows the prosthetic arm to tap into the wearer's nerves, which are like biological wires that send signals to the arm to move. It does that thanks to an invention by University of Utah biomedical engineering Emeritus Distinguished Professor Richard A. Normann called the Utah Slanted Electrode Array. The Array is a bundle of 100 microelectrodes and wires that are implanted into the amputee's nerves in the forearm and connected to a computer outside the body. The array interprets the signals from the still-remaining arm nerves, and the computer translates them to digital signals that tell the arm to move.
But it also works the other way. To perform tasks such as picking up objects requires more than just the brain telling the hand to move. The prosthetic hand must also learn how to "feel" the object in order to know how much pressure to exert because you can't figure that out just by looking at it.
First, the prosthetic arm has sensors in its hand that send signals to the nerves via the Array to mimic the feeling the hand gets upon grabbing something. But equally important is how those signals are sent. It involves understanding how your brain deals with transitions in information when it first touches something. Upon first contact of an object, a burst of impulses runs up the nerves to the brain and then tapers off. Recreating this was a big step.
"Just providing sensation is a big deal, but the way you send that information is also critically important, and if you make it more biologically realistic, the brain will understand it better and the performance of this sensation will also be better," says Clark.
To achieve that, Clark's team used mathematical calculations along with recorded impulses from a primate's arm to create an approximate model of how humans receive these different signal patterns. That model was then implemented into the LUKE Arm system.
Future Research
In addition to creating a prototype of the LUKE Arm with a sense of touch, the overall team is already developing a version that is completely portable and does not need to be wired to a computer outside the body. Instead, everything would be connected wirelessly, giving the wearer complete freedom.
Clark says the Utah Slanted Electrode Array is also capable of sending signals to the brain for more than just the sense of touch, such as pain and temperature, though the paper primarily addresses touch. And while their work currently has only involved amputees who lost their extremities below the elbow, where the muscles to move the hand are located, Clark says their research could also be applied to those who lost their arms above the elbow.
Clark hopes that in 2020 or 2021, three test subjects will be able to take the arm home to use, pending federal regulatory approval.
The research involves a number of institutions including the U's Department of Neurosurgery, Department of Physical Medicine and Rehabilitation and Department of Orthopedics, the University of Chicago's Department of Organismal Biology and Anatomy, the Cleveland Clinic's Department of Biomedical Engineering, and Utah neurotechnology companies Ripple Neuro LLC and Blackrock Microsystems. The project is funded by the Defense Advanced Research Projects Agency and the National Science Foundation.
"This is an incredible interdisciplinary effort," says Clark. "We could not have done this without the substantial efforts of everybody on that team."

Journal Reference:

1. J. A. George, D. T. Kluger, T. S. Davis, S. M. Wendelken, E. V. Okorokova, Q. He, C. C. Duncan, D. T. Hutchinson, Z. C. Thumser, D. T. Beckler, P. D. Marasco, S. J. Bensmaia, G. A. Clark. Biomimetic sensory feedback through peripheral nerve stimulation improves dexterous use of a bionic hand. Science Robotics, 2019; 4 (32): eaax2352 DOI: 10.1126/scirobotics.aax2352 

Courtesy: ScienceDaily

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'Limitless potential' of artificial protein ushers in new era of 'smart' cell therapies

Medicine has a "Goldilocks" problem. Many therapies are safe and effective only when administered at just the right time and in very precise doses -- when given too early or too late, in too large or too small an amount, medicines can be ineffective or even harmful. But in many situations, doctors have no way of knowing when or how much to dispense.

Now, a team of bioengineers led by UC San Francisco's Hana El-Samad, PhD, and the University of Washington's David Baker, PhD, have devised a remarkable solution to this problem -- "smart" cells that behave like tiny autonomous robots which, in the future, may be used to detect damage and disease, and deliver help at just the right time and in just the right amount.
Amazingly, this can be accomplished without any direct human intervention thanks to a first-of-its-kind artificial protein -- designed on a computer and synthesized in the lab -- that can be used to build brand-new biological circuits inside living cells. These circuits transform ordinary cells into smart cells that are endowed with remarkable abilities.
This new protein, formally known as the Latching Orthogonal Cage-Key pRotein, or LOCKR, is described in a pair of papers published July 24 in the journal Nature. And it's unlike anything biologists -- or nature itself -- has ever devised.
"While many tools in the biotech arsenal employ naturally occurring molecules that were repurposed for use in the lab, LOCKR has no counterpart in nature," said El-Samad, the Kuo Family Professor of Biochemistry and Biophysics at UCSF and co-senior author of the new studies. "LOCKR is a biotechnology that was conceived of and built by humans from start to finish. This provides an unprecedented level of control over the way the protein interacts with other components of the cell, and will allow us to begin tackling unsolved -- and previously unsolvable -- problems in biology, with important implications for medicine and industry."
In its structure, LOCKR resembles a barrel that, when opened, reveals a molecular arm that can be engineered to control virtually any cellular process. In the first of the two new papers, the researchers describe arms that can direct molecular traffic inside cells, degrade specific proteins, and initiate the cell's self-destruct process.
But there's a catch -- literally. LOCKR's arm remains hidden until the barrel is opened. As the protein's name suggests, the barrel stays closed until it encounters a molecular "key" -- a protein designed by scientists to fit perfectly into the barrel's "lock" -- that opens it up. In the absence of a key, LOCKR is, in effect, switched off, and the key switches it on.
The ability to control when LOCKR is "on" or "off" means that it behaves a lot like an electric switch. Though switches may seem simple, even primitive, highly miniaturized switches are the basic building block of all modern electronics, including the complex integrated circuits that power computers, iPhones, and every other smart gadget. With LOCKR, a switch-like protein, scientists can finally build the biological equivalent of such circuits inside cells.
"In the same way that integrated circuits enabled the explosion of the computer chip industry, these versatile and dynamic biological switches could soon unlock precise control over the behavior of living cells and, ultimately, our health," said El-Samad, who is also a Chan Zuckerberg Biohub Investigator.
In the second of the two papers, the researchers describe an impressive demonstration of the technology's circuit-building potential. Using a version of the tool called degronLOCKR, which can be switched on and off to degrade a protein of interest, they constructed circuits that were able to dynamically regulate cellular activity in response to cues from the cell's internal and external environment.
When the circuits, which included a genetically encoded sensor, detected a disruption of normal cell activity, degronLOCKR responded by destroying the proteins that direct the cellular "software" that caused the disruption, until the cell returned to normal -- a process reminiscent of how thermostats continually sense ambient temperature and direct HVAC systems to shut off or turn on to maintain a desired temperature.
But using degronLOCKR to construct new biological circuits like this in cells is more than a bioengineering parlor trick. According to Andrew Ng, PhD, a co-first author of the two studies who recently completed his doctoral research in El-Samad's lab, the technology's potential is virtually limitless.
"LOCKR, and more specifically, degronLOCKR, opens a whole new realm of possibility for programming cells to treat a wide range of debilitating conditions for which safe and effective treatments are not yet available," said Ng, who worked with El-Samad through the UC Berkeley-UCSF Graduate Program in Bioengineering. "With these technologies, we are constrained only by our imagination."
To that end, El-Samad, Ng and their collaborators are now building degronLOCKR-based smart cells that could treat a variety of diseases and ailments, including traumatic brain injury (TBI) -- a condition that exemplifies medicine's Goldilocks problem.
When the brain incurs a traumatic injury, the body responds by activating a vigorous inflammatory response. Though inflammation is an essential part of the body's healing process, in TBI, inflammation levels can far exceed what's necessary, or even healthy. In many cases of TBI, inflammation reaches dangerous levels that leave the brain permanently damaged.
Though doctors can administer drugs to manage this situation, they often cause inflammation to plummet to levels so low that they impede proper brain healing. With TBI, neither the body's own defenses nor modern medicine can achieve the "just right" Goldilocks level of inflammation -- not too high, not too low, but enough to maximize healing without causing permanent damage.
That's where degronLOCKR can help. The researchers think they'll soon be able to transform a patient's own cells into smart cells by installing degronLOCKR-based circuits that are designed to sense inflammation and modulate the activity of the immune system. The hope is that when these engineered cells are returned to patient's body, they'll keep inflammation well within the narrow therapeutic zone.
But TBI isn't the only condition the scientists are tackling with this technology. El-Samad thinks that smart cells could one day be deployed to treat a wide range of diseases that are currently untreatable, from cancers that are impervious to the latest drugs and cell therapies to autoimmune diseases for which no therapies are yet available.
"By using degronLOCKR and similar molecules that are slated for future development, we'll be able to compose increasingly sophisticated circuits, which may very well usher in a new generation of smart, precise and robust live cell therapies," El-Samad said.
Additional authors on the first paper include Robert A. Langan, Scott E. Boyken, Marc J. Lajoie, Zibo Chen, Stephanie Berger and Vikram Khipple Mulligan at the Institute for Protein Design at the University of Washington; Jennifer A. Samson and John E. Dueber at UC Berkeley; Galen Dods, Alexandra M. Westbrook and Taylor H. Nguyen at UCSF; and Walter R. P. Novak at Wabash College. Additional authors on the second paper include Taylor H. Nguyen, Mariana Gómez-Schiavon and Galen Dods at UCSF; Robert A. Langan and Scott E. Boyken at the Institute for Protein Design at the University of Washington; Jennifer A. Samson, Lucas M. Waldburger and John E. Dueber of UC Berkeley.
Research was supported by the Washington Research Foundation, the Burroughs Wellcome Fund, a Department of Energy BER IDAT grant (DEWAC02W05CH11231), National Institute of General Medical Sciences- supported ALSW ENABLE (GM124169W01), and a Defense Advanced Research Projects Agency contract (HR0011W16W2W0045).

Journal References:

1. Robert A. Langan, Scott E. Boyken, Andrew H. Ng, Jennifer A. Samson, Galen Dods, Alexandra M. Westbrook, Taylor H. Nguyen, Marc J. Lajoie, Zibo Chen, Stephanie Berger, Vikram Khipple Mulligan, John E. Dueber, Walter R. P. Novak, Hana El-Samad, David Baker. De novo design of bioactive protein switches. Nature, 2019; DOI: 10.1038/s41586-019-1432-8
2. Andrew H. Ng, Taylor H. Nguyen, Mariana Gómez-Schiavon, Galen Dods, Robert A. Langan, Scott E. Boyken, Jennifer A. Samson, Lucas M. Waldburger, John E. Dueber, David Baker, Hana El-Samad. Modular and tunable biological feedback control using a de novo protein switch. Nature, 2019; DOI: 10.1038/s41586-019-1425-7 

Courtesy: ScienceDaily

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Researchers wirelessly hack 'boss' gene, a step toward reprogramming the human genome

It seems like everything is going wireless these days. That now includes efforts to reprogram the human genome.

DNA and brain illustration (stock image).

Credit: © Giovanni Cancemi / Adobe Stock

A new University at Buffalo-led study describes how researchers wirelessly controlled FGFR1 -- a gene that plays a key role in how humans grow from embryos to adults -- in lab-grown brain tissue.

The ability to manipulate the gene, the study's authors say, could lead to new cancer treatments, and ways to prevent and treat mental disorders such as schizophrenia.

The work -- spearheaded by UB researchers Josep M. Jornet, Michal K. Stachowiak, Yongho Bae and Ewa K. Stachowiak -- was reported in the June edition of the Proceedings of the Institute of Electrical and Electronics Engineers.

It represents a step forward toward genetic manipulation technology that could upend the treatment of cancer, as well as the prevention and treatment of schizophrenia and other neurological illnesses. It centers on the creation of a new subfield of research the study's authors are calling "optogenomics," or controlling the human genome through laser light and nanotechnology.

"The potential of optogenomic interfaces is enormous," says co-author Josep M. Jornet, PhD, associate professor in the Department of Electrical Engineering in the UB School of Engineering and Applied Sciences. "It could drastically reduce the need for medicinal drugs and other therapies for certain illnesses. It could also change how humans interact with machines."

From "optogenetics" to "optogenomics"

For the past 20 years, scientists have been combining optics and genetics -- the field of optogenetics -- with a goal of employing light to control how cells interact with each other.

By doing this, one could potentially develop new treatments for diseases by correcting the miscommunications that occur between cells. While promising, this research does not directly address malfunctions in genetic blueprints that guide human growth and underlie many diseases.

The new research begins to tackle this issue because FGFR1 -- it stands for Fibroblast Growth Factor Receptor 1 -- holds sway over roughly 4,500 other genes, about one-fifth of the human genome, as estimated by the Human Genome Project, says study co-author Michal K. Stachowiak.

"In some respects, it's like a boss gene," says Stachowiak, PhD, professor in the Department of Pathology and Anatomical Sciences in the Jacobs School of Medicine and Biomedical Sciences at UB. "By controlling FGFR1, one can theoretically prevent widespread gene dysregulations in schizophrenia or in breast cancer and other types of cancer."

Light-activated toggle switches

The research team was able to manipulate FGFR1 by creating tiny photonic brain implants. These wireless devices include nano-lasers and nano-antennas and, in the future, nano-detectors.

Researchers inserted the implants into the brain tissue, which was grown from induced pluripotent stem cells and enhanced with light-activated molecular toggle switches. They then triggered different laser lights -- common blue laser, red laser and far-red laser -- onto the tissue.

The interaction allowed researchers to activate and deactivate FGFR1 and its associated cellular functions -- essentially hacking the gene. The work may eventually enable doctors to manipulate patients' genomic structure, providing a way to prevent and correct gene abnormalities, says Stachowiak, who also holds an appointment in UB's Department of Biomedical Engineering, a joint program between the Jacobs School and UB's engineering school.

Next steps

The development is far from entering the doctor's office or hospital, but the research team is excited about next steps, which include testing in 3D "mini-brains" and cancerous tissue. Additional study authors include Pei Miao and Amit Sangwan of the UB Department of Electrical Engineering; Brandon Decker, Aesha Desai, Christopher Handelmann of the UB Department of Pathology and Anatomical Sciences; Liang Feng, PhD, of the University of Pennsylvania; and Anna Balcerak of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Poland.

The work was supported by grants from the U.S. National Science Foundation.

Journal Reference:

1. Josep Miquel Jornet, Yongho Bae, Christopher Raymond Handelmann, Brandon Decker, Anna Balcerak, Amit Sangwan, Pei Miao, Aesha Desai, Liang Feng, Ewa K. Stachowiak, Michal K. Stachowiak. Optogenomic Interfaces: Bridging Biological Networks With the Electronic Digital World. Proceedings of the IEEE, 2019; 1 DOI: 10.1109/JPROC.2019.2916055 

Courtesy: ScienceDaily

A New Spin On DNA

Every year, robots get more and more life-like. Solar-powered bees fly on lithe wings, humanoids stick backflips, and teams of soccer bots strategize how to dribble, pass, and score. And, the more researchers discover about how living creatures move, the more machines can imitate them all the way down to their smallest molecules.

"We have these amazing machines already in our bodies, and they work so well," said Pallav Kosuri. "We just don't know exactly how they work."

For decades, researchers have chased ways to study how biological machines power living things. Every mechanical movement -- from contracting a muscle to replicating DNA -- relies on molecular motors that take tiny, near-undetectable steps.

Trying to see them move is like trying to watch a soccer game taking place on the moon.

Now, in a recent study published in Nature, a team of researchers including Xiaowei Zhuang, the David B. Arnold Professor of Science at Harvard University and a Howard Hughes Medical Institute Investigator, and Zhuang Lab postdoctoral scholar Pallav Kosuri and Benjamin Altheimer, a Ph.D. student in the Graduate School of Arts and Sciences, captured the first recorded rotational steps of a molecular motor as it moved from one DNA base pair to another.

In collaboration with Peng Yin, a professor at the Wyss Institute and Harvard Medical School, and his graduate student Mingjie Dai, the team combined DNA origami with high-precision single-molecule tracking, creating a new technique called ORBIT -- origami-rotor-based imaging and tracking -- to look at molecular machines in motion.

In our bodies, some molecular motors march straight across muscle cells, causing them to contract. Others repair, replicate or transcribe DNA: These DNA-interacting motors can grab onto a double-stranded helix and climb from one base to the next, like walking up a spiral staircase.

To see these mini machines in motion, the team wanted to take advantage of the twisting movement: First, they glued the DNA-interacting motor to a rigid support. Once pinned, the motor had to rotate the helix to get from one base to the next. So, if they could measure how the helix rotated, they could determine how the motor moved.

But there was still one problem: Every time one motor moves across one base pair, the rotation shifts the DNA by a fraction of a nanometer. That shift is too small to resolve with even the most advanced light microscopes.

Two pens lying in the shape of helicopter propellers sparked an idea to solve this problem: A propeller fastened to the spinning DNA would move at the same speed as the helix and, therefore, the molecular motor. If they could build a DNA helicopter, just large enough to allow the swinging rotor blades to be visualized, they could capture the motor's elusive movement on camera.

To build molecule-sized propellers, Kosuri, Altheimer and Zhuang decided to use DNA origami. Used to create art, deliver drugs to cells, study the immune system, and more, DNA origami involves manipulating strands to bind into beautiful, complicated shapes outside the traditional double-helix.

"If you have two complementary strands of DNA, they zip up," Kosuri said. "That's what they do." But, if one strand is altered to complement a strand in a different helix, they can find each other and zip up instead, weaving new structures.

To construct their origami propellers, the team turned to Peng Yin, a pioneer of origami technology. With guidance from Yin and his graduate student Dai, the team wove almost 200 individual pieces of DNA snippets into a propeller-like shape 160 nanometers in length. Then, they attached propellers to a regular double-helix and fed the other end to RecBCD, a molecular motor that unzips DNA. When the motor got to work, it spun the DNA, twisting the propeller like a corkscrew.

"No one had seen this protein actually rotate the DNA because it moves super-fast," Kosuri said.

The motor can move across hundreds of bases in less than a second. But, with their origami propellers and a high-speed camera running at a thousand frames per second, the team could finally record the motor's fast rotational movements.

"So many critical processes in the body involve interactions between proteins and DNA," said Altheimer. Understanding how these proteins work -- or fail to work -- could help answer fundamental biological questions about human health and disease.

The team started to explore other types of DNA motors. One, RNA polymerase, moves along DNA to read and transcribe the genetic code into RNA. Inspired by previous research, the team theorized this motor might rotate DNA in 35-degree steps, corresponding to the angle between two neighboring nucleotide bases.

ORBIT proved them right: "For the first time, we've been able to see the single base pair rotations that underlie DNA transcription," Kosuri said. Those rotational steps are, as predicted, around 35 degrees.

Millions of self-assembling DNA propellers can fit into just one microscope slide, which means the team can study hundreds or even thousands of them at once, using just one camera attached to one microscope. That way, they can compare and contrast how individual motors perform their work.

"There are no two enzymes that are identical," Kosuri said. "It's like a zoo."

One motor protein might leap ahead while another momentarily scrambles backwards. Yet another might pause on one base for longer than any other. The team doesn't yet know exactly why they move like they do. Armed with ORBIT, they soon might.

ORBIT could also inspire new nanotechnology designs powered with biological energy sources like ATP. "What we've made is a hybrid nanomachine that uses both designed components and natural biological motors," Kosuri said. One day, such hybrid technology could be the literal foundation for biologically-inspired robots.

Journal Reference:

1. Pallav Kosuri, Benjamin D. Altheimer, Mingjie Dai, Peng Yin, Xiaowei Zhuang. Rotation tracking of genome-processing enzymes using DNA origami rotors. Nature, 2019; DOI: 10.1038/s41586-019-1397-7

 Courtesy: ScienceDaily

New cell discovered that can heal hearts

University of Calgary researchers are the first to discover a previously unidentified cell population in the pericardial fluid found inside the sac around the heart. The discovery could lead to new treatments for patients with injured hearts. The study led by Drs. Paul Kubes, PhD, Justin Deniset, PhD and Paul Fedak, MD, PhD is published in the journal Immunity.

 

Heart illustration (stock image).

Credit: © abhijith3747 / Adobe Stock

The Kubes lab, in collaboration with the Fedak lab, found that a specific cell, a Gata6+ pericardial cavity macrophage, helps heal an injured heart in mice. The cell was discovered in the pericardial fluid (sac around the heart) of a mouse with heart injury. Working with Fedak, a cardiac surgeon and incoming Director of the Libin Cardiovascular Institute of Alberta, the same cells were also found within the human pericardium of people with injured hearts, confirming that the repair cells offer the promise of a new therapy for patients with heart disease.
"The fuel that powered this study is the funding from the Heart and Stroke Foundation of Canada, the collaboration between two major research institutes at CSM (Snyder and Libin) and the important contribution of philanthropy from the Libin and Snyder families to obtain imaging equipment available to very few programs globally," says Kubes, the Director of the Snyder Institute for Chronic Diseases at the Cumming School of Medicine and Professor in the Department of Physiology and Pharmacology.
Heart doctors had never before explored the possibility that cells just outside the heart could participate in healing and repair of hearts after injury. Unlike other organs, the heart has a very limited capacity to repair itself which is why heart disease is the number one cause of death in North America.
"Our discovery of a new cell that can help heal injured heart muscle will open the door to new therapies and hope for the millions of people who suffer from heart disease. We always knew that the heart sits inside a sac filled with a strange fluid. Now we know that this pericardial fluid is rich with healing cells. These cells may hold the secret to repair and regeneration of new heart muscle. The possibilities for further discovery and innovative new therapies are exciting and important," says Fedak, a professor in the Department of Cardiac Sciences.
Working together and bringing expertise across disciplines the basic researchers working with the cardiac surgeon, clinician researcher, have identified the cell in less than three years. A relatively quick time frame to move research from the lab and animal models to people.
Next Fedak hopes to recruit a basic scientist to move the research to a broader study of human heart repair. This new program will extend the collaboration between basic and clinical research to find potential new therapeutics to improve heart repair.
This research is supported by the Heart and Stroke Foundation of Canada, the Canadian Institutes of Health Research, the Canada Research Chairs Program, and the National Institutes of Health.

 Journal Reference:

1. Justin F. Deniset, Darrell Belke, Woo-Yong Lee, Selina K. Jorch, Carsten Deppermann, Ali Fatehi Hassanabad, Jeannine D. Turnbull, Guoqi Teng, Isaiah Rozich, Kelly Hudspeth, Yuka Kanno, Stephen R. Brooks, Anna-Katerina Hadjantonakis, John J. O’Shea, Georg F. Weber, Paul W.M. Fedak, Paul Kubes. Gata6+ Pericardial Cavity Macrophages Relocate to the Injured Heart and Prevent Cardiac Fibrosis. Immunity, 2019; 51 (1): 131 DOI: 10.1016/j.immuni.2019.06.010

Courtesy: ScienceDaily

Ultra-small nanoprobes could be a leap forward in high-resolution human-machine interfaces

Machine enhanced humans -- or cyborgs as they are known in science fiction -- could be one step closer to becoming a reality, thanks to new research Lieber Group at Harvard University, as well as scientists from University of Surrey and Yonsei University.

Brain circuits concept (stock image).

Credit: © santiago silver / Adobe Stock

 

Researchers have conquered the monumental task of manufacturing scalable nanoprobe arrays small enough to record the inner workings of human cardiac cells and primary neurons.
The ability to read electrical activities from cells is the foundation of many biomedical procedures, such as brain activity mapping and neural prosthetics. Developing new tools for intracellular electrophysiology (the electric current running within cells) that push the limits of what is physically possible (spatiotemporal resolution) while reducing invasiveness could provide a deeper understanding of electrogenic cells and their networks in tissues, as well as new directions for human-machine interfaces.
In a paper published by Nature Nanotechnology, scientists from Surrey's Advanced Technology Institute (ATI) and Harvard University detail how they produced an array of the ultra-small U-shaped nanowire field-effect transistor probes for intracellular recording. This incredibly small structure was used to record, with great clarity, the inner activity of primary neurons and other electrogenic cells, and the device has the capacity for multi-channel recordings.
Dr Yunlong Zhao from the ATI at the University of Surrey said: "If our medical professionals are to continue to understand our physical condition better and help us live longer, it is important that we continue to push the boundaries of modern science in order to give them the best possible tools to do their jobs. For this to be possible, an intersection between humans and machines is inevitable.
"Our ultra-small, flexible, nanowire probes could be a very powerful tool as they can measure intracellular signals with amplitudes comparable with those measured with patch clamp techniques; with the advantage of the device being scalable, it causes less discomfort and no fatal damage to the cell (cytosol dilation). Through this work, we found clear evidence for how both size and curvature affect device internalisation and intracellular recording signal."
Professor Charles Lieber from the Department of Chemistry and Chemical Biology at Harvard University said: "This work represents a major step towards tackling the general problem of integrating 'synthesised' nanoscale building blocks into chip and wafer scale arrays, and thereby allowing us to address the long-standing challenge of scalable intracellular recording.
"The beauty of science to many, ourselves included, is having such challenges to drive hypotheses and future work. In the longer term, we see these probe developments adding to our capabilities that ultimately drive advanced high-resolution brain-machine interfaces and perhaps eventually bringing cyborgs to reality."
Professor Ravi Silva, Director of the ATI at the University of Surrey, said: "This incredibly exciting and ambitious piece of work illustrates the value of academic collaboration. Along with the possibility of upgrading the tools we use to monitor cells, this work has laid the foundations for machine and human interfaces that could improve lives across the world."
Dr Yunlong Zhao and his team are currently working on novel energy storage devices, electrochemical probing, bioelectronic devices, sensors and 3D soft electronic systems. Undergraduate, graduate and postdoc students with backgrounds in energy storage, electrochemistry, nanofabrication, bioelectronics, tissue engineering are very welcome to contact Dr Zhao to explore the opportunities further.
 

Journal Reference:

1. Yunlong Zhao, Siheng Sean You, Anqi Zhang, Jae-Hyun Lee, Jinlin Huang, Charles M. Lieber. Scalable ultrasmall three-dimensional nanowire transistor probes for intracellular recording. Nature Nanotechnology, 2019; DOI: 10.1038/s41565-019-0478-y 

Courtesy: ScienceDaily
 

How trees could save the climate

Around 0.9 billion hectares of land worldwide would be suitable for reforestation, which could ultimately capture two thirds of human-made carbon emissions. The Crowther Lab of ETH Zurich has published a study in the journal Science that shows this would be the most effective method to combat climate change.

Forest (stock image).

Credit: © zlikovec / Adobe Stock

The Crowther Lab at ETH Zurich investigates nature-based solutions to climate change. In their latest study the researchers showed for the first time where in the world new trees could grow and how much carbon they would store. Study lead author and postdoc at the Crowther Lab Jean-François Bastin explains: "One aspect was of particular importance to us as we did the calculations: we ex-cluded cities or agricultural areas from the total restoration potential as these areas are needed for hu-man life."
Reforest an area the size of the USA
The researchers calculated that under the current climate conditions, Earth's land could support 4.4 billion hectares of continuous tree cover. That is 1.6 billion more than the currently existing 2.8 billion hectares. Of these 1.6 billion hectares, 0.9 billion hectares fulfill the criterion of not being used by hu-mans. This means that there is currently an area of the size of the US available for tree restoration. Once mature, these new forests could store 205 billion tonnes of carbon: about two thirds of the 300 billion tonnes of carbon that has been released into the atmosphere as a result of human activity since the Industrial Revolution.
According to Prof. Thomas Crowther, co-author of the study and founder of the Crowther Lab at ETH Zurich: "We all knew that restoring forests could play a part in tackling climate change, but we didn't really know how big the impact would be. Our study shows clearly that forest restoration is the best climate change solution available today. But we must act quickly, as new forests will take decades to mature and achieve their full potential as a source of natural carbon storage."
Russia best suited for reforestation
The study also shows which parts of the world are most suited to forest restoration. The greatest po-tential can be found in just six countries: Russia (151 million hectares); the US (103 million hectares); Canada (78.4 million hectares); Australia (58 million hectares); Brazil (49.7 million hectares); and China (40.2 million hectares).
Many current climate models are wrong in expecting climate change to increase global tree cover, the study warns. It finds that there is likely to be an increase in the area of northern boreal forests in re-gions such as Siberia, but tree cover there averages only 30 to 40 percent. These gains would be out-weighed by the losses suffered in dense tropical forests, which typically have 90 to 100 percent tree cover.
Look at Trees!
A tool on the Crowther Lab website (https://www.crowtherlab.com/maps-2/) enables users to look at any point on the globe, and find out how many trees could grow there and how much carbon they would store. It also offers lists of for-est restoration organisations. The Crowther Lab will also be present at this year's Scientifica (web-site available in German only: https://www.scientifica.ch/) to show the new tool to visitors.
The Crowther Lab uses nature as a solution to: 1) better allocate resources -- identifying those re-gions which, if restored appropriately, could have the biggest climate impact; 2) set realistic goals -- with measurable targets to maximise the impact of restoration projects; and 3) monitor progress -- to evaluate whether targets are being achieved over time, and take corrective action if necessary.
 

Journal Reference:

1. Jean-Francois Bastin, Yelena Finegold, Claude Garcia, Danilo Mollicone, Marcelo Rezende, Devin Routh, Constantin M. Zohner, Thomas W. Crowther. The global tree restoration potential. Science, 2019; 365 (6448): 76 DOI: 10.1126/science.aax0848 

Courtesy: ScienceDaily
 

HIV eliminated from the genomes of living animals

In a major collaborative effort, researchers at the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC) have for the first time eliminated replication-competent HIV-1 DNA -- the virus responsible for AIDS -- from the genomes of living animals. The study, reported online July 2 in the journal Nature Communications, marks a critical step toward the development of a possible cure for human HIV infection.

"Our study shows that treatment to suppress HIV replication and gene editing therapy, when given sequentially, can eliminate HIV from cells and organs of infected animals," said Kamel Khalili, PhD, Laura H. Carnell Professor and Chair of the Department of Neuroscience, Director of the Center for Neurovirology, and Director of the Comprehensive NeuroAIDS Center at the Lewis Katz School of Medicine at Temple University (LKSOM). Dr. Khalili and Howard Gendelman, MD, Margaret R. Larson Professor of Infectious Diseases and Internal Medicine, Chair of the Department of Pharmacology and Experimental Neuroscience and Director of the Center for Neurodegenerative Diseases at UNMC, were senior investigators on the new study.

"This achievement could not have been possible without an extraordinary team effort that included virologists, immunologists, molecular biologists, pharmacologists, and pharmaceutical experts," Dr. Gendelman said. "Only by pooling our resources together were we able to make this groundbreaking discovery."

Current HIV treatment focuses on the use of antiretroviral therapy (ART). ART suppresses HIV replication but does not eliminate the virus from the body. Therefore, ART is not a cure for HIV, and it requires life-long use. If it is stopped, HIV rebounds, renewing replication and fueling the development of AIDS. HIV rebound is directly attributed to the ability of the virus to integrate its DNA sequence into the genomes of cells of the immune system, where it lies dormant and beyond the reach of antiretroviral drugs.

In previous work, Dr. Khalili's team used CRISPR-Cas9 technology to develop a novel gene editing and gene therapy delivery system aimed at removing HIV DNA from genomes harboring the virus. In rats and mice, they showed that the gene editing system could effectively excise large fragments of HIV DNA from infected cells, significantly impacting viral gene expression. Similar to ART, however, gene editing cannot completely eliminate HIV on its own.

For the new study, Dr. Khalili and colleagues combined their gene editing system with a recently developed therapeutic strategy known as long-acting slow-effective release (LASER) ART. LASER ART was co-developed by Dr. Gendelman and Benson Edagwa, PhD, Assistant Professor of Pharmacology at UNMC.

LASER ART targets viral sanctuaries and maintains HIV replication at low levels for extended periods of time, reducing the frequency of ART administration. The long-lasting medications were made possible by pharmacological changes in the chemical structure of the antiretroviral drugs. The modified drug was packaged into nanocrystals, which readily distribute to tissues where HIV is likely to be lying dormant. From there, the nanocrystals, stored within cells for weeks, slowly release the drug.

According to Dr. Khalili, "We wanted to see whether LASER ART could suppress HIV replication long enough for CRISPR-Cas9 to completely rid cells of viral DNA."

To test their idea, the researchers used mice engineered to produce human T cells susceptible to HIV infection, permitting long-term viral infection and ART-induced latency. Once infection was established, mice were treated with LASER ART and subsequently with CRISPR-Cas9. At the end of the treatment period, mice were examined for viral load. Analyses revealed complete elimination of HIV DNA in about one-third of HIV-infected mice.

"The big message of this work is that it takes both CRISPR-Cas9 and virus suppression through a method such as LASER ART, administered together, to produce a cure for HIV infection," Dr. Khalili said. "We now have a clear path to move ahead to trials in non-human primates and possibly clinical trials in human patients within the year."

Journal Reference:

1. Prasanta K. Dash, Rafal Kaminski, Ramona Bella, Hang Su, Saumi Mathews, Taha M. Ahooyi, Chen Chen, Pietro Mancuso, Rahsan Sariyer, Pasquale Ferrante, Martina Donadoni, Jake A. Robinson, Brady Sillman, Zhiyi Lin, James R. Hilaire, Mary Banoub, Monalisha Elango, Nagsen Gautam, R. Lee Mosley, Larisa Y. Poluektova, JoEllyn McMillan, Aditya N. Bade, Santhi Gorantla, Ilker K. Sariyer, Tricia H. Burdo, Won-Bin Young, Shohreh Amini, Jennifer Gordon, Jeffrey M. Jacobson, Benson Edagwa, Kamel Khalili, Howard E. Gendelman. Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-10366-y

Courtesy: ScienceDaily