Posted on

Wireless device delivers drugs to brain and triggers neurons via remote control

Tiny, implantable devices are capable of delivering light or drugs to specific areas of the brain, potentially improving drug delivery to targeted regions of the brain and reducing side effects. Eventually, the devices may be used to treat pain, depression, epilepsy and other neurological disorders in people. (credit: Alex David Jerez Roman)

A team of researchers has developed a tiny “wireless optofluidic neural probe” the width of a human hair that can be implanted in the brain and triggered by remote control to deliver drugs and activate targeted populations of brain cells.

The technology, demonstrated for the first time in mice, may one day be used to treat pain, depression, epilepsy, and other neurological disorders in people by targeting therapies to specific brain circuits with fewer side effects, according to the researchers at Washington University School of Medicine in St. Louis and the University of Illinois at Urbana-Champaign.

Soft optofluidic neural probe during simultaneous drug delivery and photostimulation (from micro-ILED). Drugs would be delivered via the fluidic channel and activated with light as needed. (Insets) Comparison of such a device (top) and a conventional metal cannula (bottom). Scale bars, 1 mm. (credit: Jae-Woong Jeong et al./Cell)

The research builds on earlier work in optogenetics, a technology that makes individual brain cells sensitive to light and then activates those targeted populations of cells with flashes of light.

The study was published online today (July 16) in the journal Cell and will appear in the July 30 print issue.

Previous attempts to deliver drugs or other agents, such as enzymes or other compounds, to experimental animals have required the animals to be tethered to rigid pumps and tubes that restricted their movement and often caused them to experience stress.

Exploded-view schematic diagram that illustrates an array of inorganic light-emitting diodes mounted on top of a soft microfluidic system that includes four separate microfluidic channels, each connected to a set of fluid reservoirs that include copper membranes as hermetic seals, expandable composite materials as mechanical transducers, and microscale heating elements as actuators (credit: Jae-Woong Jeong et al./Cell)

The new wireless optofluidic neural probes were built with four chambers to carry drugs directly into the brain via microfluidic channels and microscale pumps, and the probes are soft like brain tissue.

New tool for mapping brain-circuit activity

A freely moving rat with head-mounted device for drug delivery and photostimulation via the optofluidic system. The device is remotely controlled via infrared technology, similar to that used in a TV remote. Scale bar, 1 cm. (credit: Jae-Woong Jeong et al./Cell)

By activating brain cells with drugs and with light, the scientists are getting an unprecedented look at the inner workings of the brain.

“This is the kind of revolutionary tool development that neuroscientists need to map out brain circuit activity,” said James Gnadt, PhD, program director at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH).

“It’s very much in line with the goals of the NIH’s BRAIN Initiative, a program designed to accelerate the development and application of new technologies to shed light on the complex links between brain function and behavior.”

The new devices may ultimately also help people with neurological disorders and other problems, according to co-first author Jae-Woong Jeong, PhD, a former postdoctoral researcher at the University of Illinois and now assistant professor of electrical, computer and energy engineering at the University of Colorado, Boulder.

“The device can remain in the brain and function for a long time without causing inflammation or neural damage,” Jeong said.

The researchers also believe that similar, more flexible devices could have applications in areas of the body other than the brain, including peripheral organs.

Messing with mice minds 

As part of the study, the researchers, who clearly are having way too much fun, showed that by delivering a drug to one side of an animal’s brain, they could stimulate neurons involved in movement, which caused the mouse to move in a circle.

In other mice, shining a light directly onto brain cells expressing a light-sensitive protein prompted the release of dopamine, a neurotransmitter that rewarded the mice by making them feel good. The mice then returned to the same location in a maze to seek another reward. But the researchers were able to interfere with that light-activated pursuit by remotely controlling the release of a drug that blocks the action of dopamine on its receptors.

The researchers hope to incorporate a design much like a printer’s ink cartridge so that drugs can continue to be delivered to specific cells in the brain, or elsewhere in the body, for as long as required and needed to replace the entire device.

Abstract of Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics

In vivo pharmacology and optogenetics hold tremendous promise for dissection of neural circuits, cellular signaling, and manipulating neurophysiological systems in awake, behaving animals. Existing neural interface technologies, such as metal cannulas connected to external drug supplies for pharmacological infusions and tethered fiber optics for optogenetics, are not ideal for minimally invasive, untethered studies on freely behaving animals. Here, we introduce wireless optofluidic neural probes that combine ultrathin, soft microfluidic drug delivery with cellular-scale inorganic light-emitting diode (m-ILED) arrays. These probes are orders of magnitude smaller than cannulas and allow wireless, programmed spatiotemporal control of fluid delivery and photostimulation. We demonstrate these devices in freely moving animals to modify gene expression, deliver peptide ligands, and provide concurrent photostimulation with antagonist drug delivery to manipulate mesoaccumbens rewardrelated behavior. The minimally invasive operation of these probes forecasts utility in other organ systems and species, with potential for broad application in biomedical science, engineering, and medicine.

Posted on

Nanospheres safely deliver high chemotherapy doses to attack tumors

Cancer tumors secrete enzymes are triggered by peptide coatings (blue) to slice the coatings open, safely delivering an anti-cancer drug (red) (credit: Cassandra E. Callmann et al./Advanced Materials)

Scientists have engineered a drug delivery system that uses specially designed nanoparticles that release drugs in the presence of a specific enzymes — the very ones that enable cancers to metastasize.

“We can start with a small molecule and build that into a nanoscale carrier that can seek out a tumor and deliver a payload of drug,” said Cassandra Callmann, a graduate student in chemistry and biochemistry at the University of California, San Diego, and first author of the report published in the journal Advanced Materials July 14.

Trojan-horse strategy

The system takes advantage of a class of enzymes called matrix metalloproteinases (MMPs) that many cancers make in abundance. MMPs normally chew through through the body’s membranes, allowing cancer cells to escape to metastasize (colonize other regions of the body), often with deadly consequences.

Trojan-horse strategy: an anti-cancer drug (Paclitaxel) and a peptide self-assemble into nanoparticles. Released at the cancer location, the peptide shell triggers cancer-cell enzymes (MMP) to rip apart the nanoparticle shell, releasing the drug (credit: Cassandra E. Callmann/Advanced Materials)

So Callmann created tiny spheres packed with the anti-cancer drug paclitaxel (also known by the trade names Taxol and Onxal) and coated with a peptide shell. When MMPs sense the peptide, they go pitbull on it, tearing up that shell, and releasing the drug. The shell fragments form a ragged mesh that holds the drug molecules near the tumor.

The work, led by Nathan Gianneschi a professor of chemistry and biochemisty at UC San Diego, builds on his group’s earlier success using a similar strategy to mark tumors for both diagnosis and precise surgical removal.

16 times higher anti-cancer dose safely administered

To package the drug into the spheres, Callmann had to add chemical handles. As it turns out, a group of atoms essential to the drug molecule’s effectiveness, and also toxicity, made for a good attachment point. That means the drug was safely inactivated as it flowed through the circulatory system until it reached the tumor.

The protection allowed the researchers to safely give a dose 16 times higher than they could with the formulation now used in cancer clinics, in a test in mice with grafted in fibrosarcoma tumors.

In additional preliminary tests, Callmann and colleagues were able to halt the growth of the tumors for a least two weeks, using a single lower dose of the drug. In mice treated with the nanoparticles that were coated with peptides that are instead impervious to MMPs or given saline, the tumors grew to lethal sizes within that time.

Gianneschi says they will broaden their approach to create delivery systems for other diagnostic and therapeutic molecules. “This kind of platform is not specific to paclitaxel. We’ll test this in other models — with other classes of drug and in mice with a cancer that mimics metastatic breast cancer, for example.”

They’ll also continue to modify the shell, to provide even greater protection and avoid uptake by organs such as liver, spleen and kidneys, he said. “We want to open up this therapeutic window.”

Abstract of Therapeutic Enzyme-Responsive Nanoparticles for Targeted Delivery and Accumulation in Tumors

An enzyme-responsive, paclitaxel-loaded nanoparticle is described and assessed in vivo in a human fibrosarcoma murine xenograft. This work represents a proof-of-concept study demonstrating the utility of enzyme-responsive nanoscale drug carriers capable of targeted accumulation and retention in tumor tissue in response to overexpressed endogenous enzymes.

Posted on

Continued destruction of Earth’s plant life places humankind in jeopardy, say researchers

Earth-space battery. The planet is a positive charge of stored chemical energy (cathode) in the form of fossil and nuclear fuels and biomass. As this energy is dissipated by humans, it eventually radiates as heat toward the chemical equilibrium of deep space (anode). The battery is rapidly discharging without replenishment. (credit: John R. Schramski et al./PNAS)

Unless humans slow the destruction of Earth’s declining supply of plant life, civilization like it is now may become completely unsustainable, according to a paper published recently by University of Georgia researchers in the Proceedings of the National Academy of Sciences.

“You can think of the Earth like a battery that has been charged very slowly over billions of years,” said the study’s lead author, John Schramski, an associate professor in UGA’s College of Engineering. “The sun’s energy is stored in plants and fossil fuels, but humans are draining energy much faster than it can be replenished.”

Number of years of phytomass food potentially available to feed the global human population (credit: John R. Schramski et al./PNAS)

Earth was once a barren landscape devoid of life, he explained, and it was only after billions of years that simple organisms evolved the ability to transform the sun’s light into energy. This eventually led to an explosion of plant and animal life that bathed the planet with lush forests and extraordinarily diverse ecosystems.

The study’s calculations are grounded in the fundamental principles of thermodynamics, a branch of physics concerned with the relationship between heat and mechanical energy. Chemical energy is stored in plants, or biomass, which is used for food and fuel, but which is also destroyed to make room for agriculture and expanding cities.

Scientists estimate that the Earth contained approximately 1,000 billion tons of carbon in living biomass 2,000 years ago. Since that time, humans have reduced that amount by almost half. It is estimated that just over 10 percent of that biomass was destroyed in just the last century.

“If we don’t reverse this trend, we’ll eventually reach a point where the biomass battery discharges to a level at which Earth can no longer sustain us,” Schramski said.

Major causes: deforestation, large-scale farming, population growth

Working with James H. Brown from the University of New Mexico, Schramski and UGA’s David Gattie, an associate professor in the College of Engineering, the research shows that the vast majority of losses come from deforestation, hastened by the advent of large-scale mechanized farming and the need to feed a rapidly growing population. As more biomass is destroyed, the planet has less stored energy, which it needs to maintain Earth’s complex food webs and biogeochemical balances.

NASA Earth Observatory biomass map of the U.S. by Robert Simmon, generated from the National Biomass and Carbon Dataset (NBCD) assembled by scientists at the Woods Hole Research Center

“As the planet becomes less hospitable and more people depend on fewer available energy options, their standard of living and very survival will become increasingly vulnerable to fluctuations, such as droughts, disease epidemics and social unrest,” Schramski said.

If human beings do not go extinct, and biomass drops below sustainable thresholds, the population will decline drastically, and people will be forced to return to life as hunter-gatherers or simple horticulturalists, according to the paper.

“I’m not an ardent environmentalist; my training and my scientific work are rooted in thermodynamics,” Schramski said. “These laws are absolute and incontrovertible; we have a limited amount of biomass energy available on the planet, and once it’s exhausted, there is absolutely nothing to replace it.”

Schramski and his collaborators are hopeful that recognition of the importance of biomass, elimination of its destruction and increased reliance on renewable energy will slow the steady march toward an uncertain future, but the measures required to stop that progression may have to be drastic.

The model does not take into account potential future breakthroughs in more efficient biomass use and alternate energy systems.

Abstract of Human domination of the biosphere: Rapid discharge of the earth-space battery foretells the future of humankind

Earth is a chemical battery where, over evolutionary time with a trickle-charge of photosynthesis using solar energy, billions of tons of living biomass were stored in forests and other ecosystems and in vast reserves of fossil fuels. In just the last few hundred years, humans extracted exploitable energy from these living and fossilized biomass fuels to build the modern industrial-technological-informational economy, to grow our population to more than 7 billion, and to transform the biogeochemical cycles and biodiversity of the earth. This rapid discharge of the earth’s store of organic energy fuels the human domination of the biosphere, including conversion of natural habitats to agricultural fields and the resulting loss of native species, emission of carbon dioxide and the resulting climate and sea level change, and use of supplemental nuclear, hydro, wind, and solar energy sources. The laws of thermodynamics governing the trickle-charge and rapid discharge of the earth’s battery are universal and absolute; the earth is only temporarily poised a quantifiable distance from the thermodynamic equilibrium of outer space. Although this distance from equilibrium is comprised of all energy types, most critical for humans is the store of living biomass. With the rapid depletion of this chemical energy, the earth is shifting back toward the inhospitable equilibrium of outer space with fundamental ramifications for the biosphere and humanity. Because there is no substitute or replacement energy for living biomass, the remaining distance from equilibrium that will be required to support human life is unknown.

Posted on

Memory-loss case ‘like nothing we have ever seen before’

(credit: Newmarket Films)

Gerald Burgess, a University of Leicester lecturer in clinical psychology, has described treating an individual who suffered a “Memento/Before I Go to Sleep“-style anterograde amnesia memory loss after a treatment at a dentist — “like nothing we have ever seen before.”

Since the one-hour root-canal treatment, during which the a 38-year-old man from the UK was given a local anesthetic, the individual cannot remember anything beyond 90 minutes.

He is fully aware of his identity and his personality did not change, says Burgess, but every day the man thinks it is the day of his dental appointment. He has to manage his life through an electronic diary and access to prompts.

Burgess has now described the study, done a decade ago, in an open-access paper published in May in the journal Neurocase. He is also appealing for people who know of someone who might have suffered similar symptoms of memory loss, or medical or allied health professionals working with someone like this, to contact him to build up knowledge and evidence in this field of study.

Possible explanations

Burgess notes that “what we did know about from decades of research and hundreds of case studies, is that bilateral damage to the hippocampal and/or diencephalon structures causes profound amnesia … [but] we should perhaps not be so stuck in thinking that profound amnesia only occurs in the context of visible damage to the brain’s hippocampal and/or diencephalon structures.

“Those structures appear just to be needed for the initial holding or retention of information before engrams then proceed slowly through several other neuro-electrical and neuro-chemical events, before finally permanent memories are stored, and that something can occur at some later point in this process to vanquish the memory trace permanently.

“An acquired or manifest deficiency of protein synthesis, required for permanent re-structuring of synapses in the brain, seemed an intriguing speculation, and one we hope there might be further human research into. This speculation was sparked by two seemingly key coincidences of one, timing when this protein synthesis stage occurs coincides with the patient’s forgetting at 90 minutes or thereabouts, and two, both ‘episodic’ and ‘procedural’ memories appear to require successful protein synthesis to occur for long-term memory permanence, and the patient cannot retain any new either episodic or procedural memories — and this is unusual compared to traditional cases of amnesia.”

The work was done in collaboration with Bhanu Chadalavada Consultant Psychiatrist at Northamptonshire Healthcare Foundation NHS Trust.


Newmarket | Memento (2000) (HD Trailer)

A man creates a strange system to help him remember things; so he can hunt for the murderer of his wife without his short-term memory loss being an obstacle.


Scott Free | Before I Go To Sleep Official Trailer #1 (2014) – Nicole Kidman, Colin Firth Movie HD

A woman wakes up every day, remembering nothing as a result of a traumatic accident in her past. One day, new terrifying truths emerge that force her to question everyone around her.


Columbia Pictures | 50 First Dates Trailer

A man afraid of commitment thinks he’s finally found the girl of his dreams, until he discovers she has short-term memory loss and forgets him the very next day.

Abstract of Profound anterograde amnesia following routine anesthetic and dental procedure: a new classification of amnesia characterized by intermediate-to-late-stage consolidation failure?

Anterograde amnesia caused by bilateral hippocampal or diencephalon damage manifests in characteristic symptoms of preserved intellect and implicit learning, and short span of awareness with complete and rapid forgetting of episodic material. A new case, WO, 38-year-old male with anterograde amnesia, in the absence of structural brain changes or psychological explanation is presented, along with four comparison cases from the extant literature that share commonalities between them including preserved intellect, span of awareness greater than working memory, and complete forgetting within hours or days following successful learning, including notably for both explicit and implicit material. WO’s amnesia onset coincided with anesthetic injection and root canal procedure, with extended vasovagal-like incident. The commonalities between the five cases presented may suggest a shared biological mechanism involving the breakdown of intermediate-to-late-stage consolidation that does not depend on the structural integrity of the hippocampi. Speculation on the mechanism of consolidation breakdown and diagnostic implications are discussed.

Posted on

A jet engine powered by lasers and nuclear explosions?

Lasers vaporize radioactive material and cause a fusion reaction — in effect, a small thermonuclear explosion (credit: Patent Yogi/YouTube)

The U.S. Patent and Trademark Office has awarded a patent (US 9,068,562) to Boeing engineers and scientists for a laser- and nuclear-driven airplane engine.

“A stream of pellets containing nuclear material such as Deuterium or Tritium is fed into a hot-stop within a thruster of the aircraft,” Patent Yogi explains. “Then multiple high powered laser beams are all focused onto the hot-spot. The pellet is instantly vaporized and the high temperature causes a nuclear fusion reaction. In effect, it causes a tiny nuclear explosion that scatters atoms and high energy neutrons in all directions. This flow of material is concentrated to exit out of the thruster thus propelling the aircraft forward with great force.

“And this is where Boeing has done something extremely clever. The inner walls of the thurster are coated with a fissile material like Uranium-238 that undergoes a nuclear fission upon being struck by the high energy neutrons. This releases enormous energy in the form of heat. A coolant is circulated along the inner walls to pick up this heat and power a turbine which in turn generates huge amounts of electric power. And guess what this electric power is used for? To power the same lasers that created the electric power! In effect, this space-craft is self-powered with virtually no external energy needed.

“Soon, tiny nuclear bombs exploding inside a plane may be business as usual.”

An artist’s conception of the NASA reference design for the Project Orion spacecraft powered by nuclear propulsion (credit: NASA)

The basic concept was initially proposed by physicist Freeman Dyson in his Project Orion concept in 1957 and described on George Dyson’s Project Orion — The Atomic Spaceship 1957-1965 book.

Posted on

‘Smart clothes’ for personalized cooling and heating

Garment-based printable electrodes (credit: UC San Diego)

Instead of heating or cooling your whole house, imagine a fabric that will keep your body at a comfortable temperature — regardless of how hot or cold it actually is.

That’s the goal of an engineering project called ATTACH (Adaptive Textiles Technology with Active Cooling and Heating) at the University of California, San Diego, funded with a $2.6M grant from the U.S. Department of Energy’s Advanced Research Projects Agency – Energy (ARPA-E).

By regulating the temperature around an individual person, rather than a large room, the smart fabric could potentially cut the energy use of buildings and homes by at least 15 percent, said project leader Joseph Wang, distinguished professor of nanoengineering at UC San Diego.

“In cases where there are only one or two people in a large room, it’s not cost-effective to heat or cool the entire room,” said Wang. “If you can do it locally, like you can in a car by heating just the car seat instead of the entire car, you can save a lot of energy.”

Skin temperature

The smart fabric will be designed to regulate the temperature of the wearer’s skin — keeping it at 93° F — by adapting to temperature changes in the room. When the room gets cooler, the fabric will become thicker. When the room gets hotter, the fabric will become thinner, using polymers inside the smart fabric that expand in the cold and shrink in the heat.

“93° F is the average comfortable skin temperature for most people,” added Renkun Chen, assistant professor of mechanical and aerospace engineering at UC San Diego, and one of the collaborators on this project.

The clothing will incorporate printable “thermoelectrics” into specific spots of the smart fabric to regulate the temperature on “hot spots” — such as areas on the back and underneath the feet — that tend to get hotter than other parts of the body when a person is active.

Saving energy

“With the smart fabric, you won’t need to heat the room as much in the winter, and you won’t need to cool the room down as much in the summer. That means less energy is consumed,” said Chen.

The researchers are also designing the smart fabric to power itself, using rechargeable batteries to power the thermoelectrics and biofuel cells that can harvest electrical power from human sweat.

The 3-D printable wearable parts will be thin, stretchable, and flexible to ensure that the smart fabric is not bulky or heavy. The material will also be washable, stretchable, bendable and lightweight.

“We also hope to make it look attractive and fashionable to wear,” said Wang.

 

Posted on

3-D printed food

(credit: excerpt from cover of Fabricated: The New World of 3D Printing by Tod Lipson)

3D printers could revolutionize food processing in the next 10 to 20 years, said Hod Lipson, Ph.D., a professor of engineering at Columbia University, speaking at IFT15: Where Science Feeds Innovation.

“The technology is getting faster, cheaper, and better by the minute. Food printing could be the killer app for 3D printing.”

Lipson, who is co-author of Fabricated: The New World of 3D Printing, said 3D printing is a good fit for the food industry because it allows manufacturers to bring complexity and variety to consumers at a low cost.

For example, Lipson said, users could choose from a large online database of recipes, put a cartridge with the ingredients into their 3D printer at home, and it would create the dish just for that person. The user could customize it to include extra nutrients or replace one ingredient with another.

Mary Scerra, food technologist at the U.S. Army Natick Soldier Research, Development and Engineering Center (NSRDEC) said that by 2025 or 2030, the military envisions using 3D printing to customize meals for soldiers that “taste good [seriously?], are nutrient-dense, and could be tailored to a soldier’s particular needs.”

Posted on

Using graphene-based film for efficient cooling of electronics

Graphene-based film on a hot electronic component (credit: Johan Liu)

A method for efficiently cooling electronics using graphene-based film — with a thermal conductivity capacity four times higher than copper — has been developed by researchers at Chalmers University of Technology. The film can be attached to computer chips and other silicon-based electronic components.

Electronic systems available today accumulate a great deal of heat, mostly due to the ever-increasing demand on functionality. Getting rid of excess heat in efficient ways is needed for chip lifespan and reduction in energy usage.

A research team led by Johan Liu, a professor at Chalmers University of Technology, originally found that graphene can have a cooling effect on silicon-based electronics, but that it’s not efficient because it’s limited to a few layers of graphene atoms. “When you try to add more layers of graphene, the graphene will no longer adhere to the surface, since the adhesion is [due to] weak van der Waals bonds,” he said.

Silane coupling between graphene and silicon. After heating and hydrolysis of (3-Aminopropyl) triethoxysilane (APTES) molecules (top right), silane coupling (bottom right) is created, providing mechanical strength and good thermal pathways (credit: Johan Liu)

The researchers solved that by creating strong covalent bonds between the graphene film and the surface. The stronger bonds result from adding (3-Aminopropyl) triethoxysilane (APTES) molecules to the film. Heating and hydrolysis then creates silane bonds between the graphene and the electronic component, doubling thermal conductivity.

“Increased thermal capacity could lead to several new [cooling] applications for graphene,” says Liu, including LEDs, lasers, and radio frequency components.

Abstract of Improved Heat Spreading Performance of Functionalized Graphene in Microelectronic Device Application

It is demonstrated that a graphene-based film (GBF) functionalized with silane molecules strongly enhances thermal performance. The resistance temperature detector results show that the inclusion of silane molecules doubles the heat spreading ability. Furthermore, molecular dynamics simulations show that the thermal conductivity (κ) of the GBF increased by 15%–56% with respect to the number density of molecules compared to that with the nonfunctionalized graphene substrate. This increase in κ is attributed to the enhanced in-plane heat conduction of the GBF, resulting from the simultaneous increase of the thermal resistance between the GBF and the functionalized substrate limiting cross-plane phonon scattering. Enhancement of the thermal performance by inserting silane-functionalized molecules is important for the development of next-generation electronic devices and proposed application of GBFs for thermal management.

Posted on

Gene therapy restores hearing in deaf mice

The inverted V’s above are sensory hair bundles in the ear, each containing 50 to 100 microvilli tipped with TMC proteins. Gene therapy restores hearing by providing working copies of those proteins. (credit: Gwenaelle Geleoc & Artur Indzhykulian)

Patients with hearing loss will one day have their genome sequenced and their hearing restored by gene therapy, says Jeffrey Holt, PhD,  a scientist in the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and an associate professor of Otolaryngology at Harvard Medical School.

A proof-of-principle study published by the journal Science Translational Medicine takes a step in that direction, restoring hearing in deaf mice. Clinical trials of gene therapy for humans could be started within 5 to 10 years, Holt believes.

Holt, with first author Charles Askew and colleagues at École Polytechnique Fédérale de Lausanne in Switzerland, focused on deafness caused by a gene called TMC1 — one of more than 70 different genes are known to cause deafness when mutated. TMC1 accounts for 4 to 8 percent of genetic deafness, and also encodes a protein that’s critical for hearing by helping to convert sound into electrical signals that travel to the brain.

To deliver the functioning TMC1 gene into the ear, the team inserted it into an engineered virus called adeno-associated virus 1, or AAV1, and added a promoter, a genetic sequence that turns the gene on only in certain sensory cells in the cochlea, known as hair cells.

“I heard that!” Rasbak/Wikimedia Commons

They then injected the engineered AAV1 into the inner ears of mutant, deaf mice modeling the more common recessive form of TMC1 deafness, which causes profound hearing loss in children from a very young age, usually by around 2 years. After the injection, the animals’ sensory hair cells began responding to sound and electrical activity began showing up in the auditory portion of their brainstems.

How it works

Holt’s team showed in 2013 that TMC1 and the related protein TMC2 are critical for hearing, ending a rigorous 30-year search by scientists. Sensory hair cells contain tiny projections called microvilli, each tipped with a channel formed by TMC1 and TMC2 proteins. Arriving sound waves wiggle the microvilli, causing the channels to open. That allows calcium to enter the cell, generating an electrical signal that travels to the brain and ultimately translates to hearing.

Although the channel is made up of either TMC1 or TMC2, a mutation in the TMC1 gene is sufficient to cause deafness. However, Holt’s study also showed that gene therapy with the TMC2 gene could compensate for loss of a functional TMC1, restoring hearing in the recessive deafness model and partial hearing in a mouse model of dominant TMC1 deafness, in which patients gradually go deaf beginning around 10 to 15 years of age.

Abstract of Tmc gene therapy restores auditory function in deaf mice

Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genetic hearing loss, we tested a gene augmentation approach in mouse models of genetic deafness. We focused on DFNB7/11 and DFNA36, which are autosomal recessive and dominant deafnesses, respectively, caused by mutations in transmembrane channel–like 1 (TMC1). Mice that carry targeted deletion of Tmc1 or a dominant Tmc1 point mutation, known as Beethoven, are good models for human DFNB7/11 and DFNA36. We screened several adeno-associated viral (AAV) serotypes and promoters and identified AAV2/1 and the chicken β-actin (Cba) promoter as an efficient combination for driving the expression of exogenous Tmc1 in inner hair cells in vivo. Exogenous Tmc1 or its closely related ortholog, Tmc2, were capable of restoring sensory transduction, auditory brainstem responses, and acoustic startle reflexes in otherwise deaf mice, suggesting that gene augmentation with Tmc1 or Tmc2 is well suited for further development as a strategy for restoration of auditory function in deaf patients who carry TMC1 mutations.

Posted on

IBM announces first 7nm node test chips

7nm node test chips (credit: Darryl Bautista/IBM)

IBM Research has announced the semiconductor industry’s first 7nm (nanometer) node test chips, which could allow for chips with more than 20 billion transistors, IBM believes — a big step forward from today’s most advanced chips, made using 14nm technology.

IBM achieved the 7 nm node through a combination of new materials, tools and techniques, explained Mukesh Khare, VP, IBM Semiconductor Technology Research in a blog post. “In materials, we’re using silicon germanium for the first time in the channels on the chips that conduct electricity. We have employed a new type of lithography in the chip-making process, Extreme Ultraviolet, or EUV, which delivers order-of-magnitude improvements over today’s mainstream optical lithography.”

However, as future technology starts to hit the quantum wall, “there’s no clear path to extend the life of the silicon semiconductor further into the future,” he noted.  “The next major wave of progress, the 5 nm node, will be even more challenging than the 7 nm node has been.”

IBM 7nm node test chip closeup (credit: Darryl Bautista/IBM)

Meanwhile, industry experts consider 7nm technology crucial to meeting the anticipated demands of future cloud computing and Big Data systems, cognitive computing, mobile products and other emerging technologies, says IBM. Part of IBM’s $3 billion, five-year investment in chip R&D (announced in 2014), this accomplishment was the result of a  public-private partnership with New York State and joint development alliance with GLOBALFOUNDRIES, Samsung, and equipment suppliers.

When will it be available in products? IBM “declined to speculate on when it might begin commercial manufacturing of this technology generation,” The New York Times reports. Intel’s public roadmap indicates that it’s also working on a 7 nanometer chip, Wired notes.