Neuroscientists at the University of Pittsburgh have identified the neural networks that connect the cerebral cortex to the adrenal medulla — the inner part of the adrenal gland, located above each kidney, which is responsible for the body’s rapid response in stressful situations.
These findings, reported in the online Early Edition of the journal Proceedings of the National Academy of Sciences PNAS), provide evidence for the neural basis of a mind-body connection. They also shed new light on how stress, depression, and other mental states can alter organ function, and show that there is a real anatomical basis for psychosomatic illness.
The research also identifies a concrete neural substrate that may help explain why meditation and certain exercises such as yoga and Pilates can be so helpful in modulating the body’s responses to physical, mental and emotional stress, according to senior author Peter L. Strick, Ph.D., Thomas Detre Chair of the Department of Neurobiology and scientific director of the University of Pittsburgh Brain Institute.
Why it matters which cortical areas influence the adrenal medulla
In their experiments with monkeys, the scientists traced the neural circuitry that links areas of the cerebral cortex to the adrenal medulla, using a unique tracing method that involves rabies virus. This approach is capable of revealing long chains of interconnected neurons.
Another surprising result of the research was that motor areas in the cerebral cortex, which are involved in the planning and performance of movement, provide a substantial input to the adrenal medulla. One of these areas is a portion of the primary motor cortex that is concerned with the control of axial body movement and posture. This input to the adrenal medulla may explain why core body exercises are so helpful in modulating responses to stress. Calming practices such as Pilates, yoga, tai chi and even dancing in a small space all require proper skeletal alignment, coordination, and flexibility to avoid harm to the body.
The PNAS study also revealed that the areas of the cortex that are active when we sense conflict, or are aware that we have made an error, are a source of influence over the adrenal medulla. “This observation,” said Dr. Strick, “raises the possibility that activity in these cortical areas when you re-imagine an error, or beat yourself up over a mistake, or think about a traumatic event, results in descending signals that influence the adrenal medulla in just the same way as the actual event.”
These anatomical findings have relevance for therapies that deal with post-traumatic stress.
Additional links with the adrenal medulla were discovered in cortical areas that are active during mindful mediation and areas that show changes in bipolar familial depression. “One way of summarizing our results is that we may have uncovered the stress and depression connectome,” says Strick.
Overall, these results indicate that circuits exist to link movement, cognition and affect to the function of the adrenal medulla and the control of stress. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and thus provide a concrete neural substrate for some psychosomatic illness.
Modern medicine has generally viewed the concept of “psychosomatic” disease with suspicion. This view arose partly because no neural networks were known for the mind, conceptually associated with the cerebral cortex, to influence autonomic and endocrine systems that control internal organs. Here, we used transneuronal transport of rabies virus to identify the areas of the primate cerebral cortex that communicate through multisynaptic connections with a major sympathetic effector, the adrenal medulla. We demonstrate that two broad networks in the cerebral cortex have access to the adrenal medulla. The larger network includes all of the cortical motor areas in the frontal lobe and portions of somatosensory cortex. A major component of this network originates from the supplementary motor area and the cingulate motor areas on the medial wall of the hemisphere. These cortical areas are involved in all aspects of skeletomotor control from response selection to motor preparation and movement execution. The second, smaller network originates in regions of medial prefrontal cortex, including a major contribution from pregenual and subgenual regions of anterior cingulate cortex. These cortical areas are involved in higher-order aspects of cognition and affect. These results indicate that specific multisynaptic circuits exist to link movement, cognition, and affect to the function of the adrenal medulla. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and, thus, provide a concrete neural substrate for some psychosomatic illness.
Mayo Clinic and other members of the Geroscience Network* have developed strategies for taking new drugs to clinical trials — specifically, drugs that target processes underlying multiple age-related diseases and disabilities. And they’ve written six supporting articles that appeared Wednesday Aug. 17 in The Journals of Gerontology: Series A – Biological Sciences and Medical Sciences.
The Geroscience Network consists of 18 academic aging center, with the participation of more than 100 investigators from across the U.S. and Europe.
Aging may be a modifable risk factor
“Aging is the largest risk factor for most chronic diseases, including stroke, heart disease, cancer, dementias, osteoporosis, arthritis, diabetes, metabolic syndrome, blindness and frailty,” said James Kirkland, M.D., Ph.D., director of the Mayo Clinic Robert and Arlene Kogod Center on Aging.
However, he said recent research suggests that aging may actually be a modifiable risk factor. “The goal of our network’s collaborative efforts is to accelerate the pace of discovery in developing interventions to delay, prevent, or treat these conditions as a group, instead of one at a time.”
Felipe Sierra, Ph.D., of the National Institute on Aging and a member of the Geroscience Network, describes the potential impact of such discoveries in his article, “Moving Geroscience into Uncharted Waters.” He notes that in addition to the direct health issues, care for the elderly currently accounts for 43 percent of the total health care spending in the U.S,, or approximately 1 trillion dollars a year, and that this number is expected to rise as baby boomers reach retirement age.
“Reducing these costs is critical for the survival of society as we know it,” he said. “A 2013 paper by Dana Goldman and colleagues calculated that a just modest increase (2.2 years) in lifespan and healthspan could reduce those expenses by 7 trillion dollars by 2050.”
This work was supported by the National Institutes of Health, the Paul Glenn Foundation, Nathan Shock Centers of Excellence for the Biology of Aging, the Connor Group, and the Noaber and Ted Nash foundations.
The first two articles cited below are open-access.
* In addition to Mayo Clinic, members of the Geroscience Network are Albert Einstein College of Medicine, Buck Institute for Research on Aging, Harvard University, Johns Hopkins University, National Institute on Aging, the Scripps Research Institute, Stanford University, the University of Alabama at Birmingham, the University of Arkansas, the University of Connecticut, the University of Michigan, the University of Minnesota, the University of Oklahoma, the University of Texas Health Science Center San Antonio, the University of Southern California, the University of Washington, and Wake Forest University as well as members from other institutions across the U.S. and Europe.
Researchers at McMaster University in Canada have developed a radically improved way to purify single-wall carbon nanotubes (SWNTs) — flexible structures that are one nanometer in diameter and thousands of times longer, and that may revolutionize computers and electronics, replacing silicon.
To do that, we need to separate out semiconducting (sc-SWNTs) and metallic (m-SWNTs) nanotubes. That’s a challenging problem, because both are created simultaneously in the process* of producing carbon nanotubes.
“Once we have a reliable source of pure nanotubes that are not very expensive, a lot can happen very quickly,” says Alex Adronov, a professor of Chemistry at McMaster whose research team has developed a new and potentially cost-efficient way to purify carbon nanotubes.
Separating out semiconducting carbon nanotubes
Previous researchers have created polymers that could allow semiconducting carbon nanotubes to be dissolved and washed away, leaving metallic nanotubes behind, but there has not been such a process for doing the more-useful opposite: dispersing the metallic nanotubes and leaving behind the valuable semiconducting structures.
Now, Adronov’s research group has reversed the electronic characteristics (from electron-rich to electron-poor) of a polymer known to disperse semiconducting nanotubes, while leaving the rest of the polymer’s structure intact. That is, they have reversed the purification process — leaving the semiconducting nanotubes behind while making it possible to disperse the metallic nanotubes.**
The next step, he explains, is for his team or other researchers to exploit the discovery by finding a way to develop even more efficient polymers and scale up the process for commercial production.
The unique properties of SWNTs — high tensile strength, the high aspect ratio, thermal and electrical conductivity, and extraordinary optical characteristics — could make carbon nanotubes potentially valuable as advanced materials in a variety of applications, including “field-effect transistors, photovoltaics, flexible electronics, sensors, touch screens, high-strength fibers, biotechnological constructs, and various other devices,” the researchers note in the current cover story of Chemistry – A European Journal.
Financial support for this work was provided by the Discovery and Strategic Grant programs of the Natural Science and Engineering Research Council (NSERC) of Canada.
* These processes include high-pressure carbon monoxide disproportionation (HiPCO),carbon vapor deposition (CVD),arc discharge,laser ablation, and plasma torch growth.
** “We expect that relatively electron-poor conjugated polymers should disperse m-SWNTs to a greater extent when compared to structurally similar electron-rich conjugated polymers. Here, we demonstrate this concept through the comparison of a poly(fluorene-co-pyridine) conjugated polymer before and after post-polymerization functionalization. By partially methylating the pyridine units, cationic charges are introduced onto the conjugated backbone, which convert the polymer from being electron-rich to electron-poor. This enables the comparison of two polymers that are identical in length and polydispersity, and differ primarily in their electronic characteristics. We show that the electron-poor conjugated polymer results in dispersions that are enriched in m-SWNTs, while the electron-rich counterpart solely selects for sc-SWNTs, thus providing evidence that the electronic structure of a conjugated polymer plays an important role in determining its selectivity for different SWNT types.” — Darryl Fong et al./Chemistry – A European Journal.
Abstract of Influence of Polymer Electronics on Selective Dispersion of Single-Walled Carbon Nanotubes
In the pursuit of next-generation polymers for the selective dispersion and purification of single-walled carbon nanotubes (SWNTs), understanding the key parameters dictating polymer selectivity is imperative. Simple modification of a poly(fluorene-co-pyridine) backbone, such that it is transformed from being electron-rich to -poor, has a significant impact on the electronic nature of the SWNTs dispersed. The unmodified copolymer bearing an electron-rich fluorene co-monomer preferentially forms stable colloids with sc-SWNTs, while the methylated copolymer bearing electron-withdrawing cationic charges produces dispersions that are more enriched with m-SWNTs.
The Rejuvenation Biotechnology Conference will be live-streamed Tuesday Aug. 16, starting at 1 PM PDT, and Wednesday Aug. 17.
The 2016 Rejuvenation Biotechnology Conference is focused on taking the Rejuvenation Biotechnology Industry to the next level by addressing the question: what will it take to push emerging breakthroughs in regenerative medicine from proof-of-concept to implementation?
This year’s conference seeks to answer this critical inquiry by covering all the stages from securing funding, to production, to navigating regulation, to clinical evaluation and adoption of new treatments. Industry leading experts will present real-life examples drawn from their own work followed by an open panel discussion and Q&A.
Register here for live-streaming access. If you want to ask a question during the live stream of the event, contact the conference via Twitter at #RejBioCon
Rejuvenation Biotechnology Conference Tuesday 16th Streaming from 1 p.m. – 6 p.m. PDT (8 p.m. – 1 a.m. GMT)
New cancer-drug delivery system uses magnetically guided bacteria to target cancerous tumors with high precision
Researchers from Polytechnique Montréal, Université de Montréal, and McGill University have designed a new cancer-drug-delivery nanotransporter system using more than 100 million flagellated, self-propelled bacteria that are capable of navigating through the bloodstream to administer a drug to tumors with precision.* The goal of the research is to avoid jeopardizing the integrity of organs and surrounding healthy tissues while reducing drug dosage.
In an experiment with mice reported in the journal Nature Nanotechnology, the researchers confirmed that “the drug’s propelling force was enough to travel efficiently and enter deep inside the tumors,” autonomously detecting the oxygen-depleted tumor areas and delivering the drug to them, said Professor Sylvain Martel, holder of the Canada Research Chair in Medical Nanorobotics and Director of the Polytechnique Montréal Nanorobotics Laboratory, who heads the research team’s work.Bacteria that detect both magnetic field lines and low-oxygen concentrations
In the experiment with mice, the researchers used liposomes as drug nanocarriers, attached to Magnetococcus marinus strain MC-1 bacteria to transport the drug**. In their natural environment, MC-1 bacteria tend to swim along local magnetic field lines, which are detected by a chain of magnetic iron-oxide nanocrystals in the bacteria. The bacteria also swim towards hypoxic (low-oxygen) concentrations. (In a tumor, this hypoxic zone is created by the substantial consumption of oxygen by rapidly proliferative tumor cells. Hypoxic zones are known to be resistant to most therapies, including radiotherapy.)
The new nanotransporters used both of these natural systems (magnetic and hypoxic-concentration-seeking). The MC-1 bacteria first moved in the direction of a computer-controlled magnetic field to the point where oxygen gradients could be detected by the bacteria, enabling the bacteria to penetrate and remain in the tumor’s active regions. (In future human use, the drug could be released from the liposomes by sensing pH or particular enzymes, or by applying ultrasonics or heat, for example, the researchers explained to KurzweilAI.)
“This innovative use of nanotransporters will have an impact not only on creating more advanced engineering concepts and original intervention methods, but it also throws the door wide open to the synthesis of new vehicles for therapeutic, imaging, and diagnostic agents,” said Martel. Chemotherapy, which is so toxic for the entire human body, could make use of these natural nanotransporters to move drugs directly to the targeted area, “eliminating the harmful side effects while also boosting its therapeutic effectiveness,” he added.
The research was supported by the Consortium québécois sur la découverte du médicament (Québec consortium for drug discovery — CQDM), the Canada Research Chairs, the Natural Sciences and Engineering Research Council of Canada (NSERC), the Research Chair in Nanorobotics of Polytechnique Montréal, Mitacs, the Canada Foundation for Innovation (CFI), and the National Institutes of Health (NIH). Montréal’s Jewish General Hospital, the McGill University Health Centre (MUHC), the Institute for Research in Immunology and Cancer (IRIC), and the Rosalind and Morris Goodman Cancer Research Centre also participated.
* Only ∼2% of the total administered dose is deposited in the tumor with current delivery methods, according to a 2009 study by M. Hong et al. in J. Control. Rel., the researchers note in their Nature Nanotechnology paper.
** “Liposomes were selected as a first proof of concept because they are biocompatible, exhibit low immunogenicity and high flexibility, and protect the body from potential toxic cargo. Liposomes also shield therapeutic agents from premature degradation, control release kinetics, and may encapsulate a multitude of hydrophilic and∕or hydrophobic drug cargos, pharmaceutical ingredients, imaging agents and genetic material by virtue of their aqueous interior and lipid exterior,” the researchers note in their Nature Nanotechnology paper.
Abstract of Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions
POLYTECHNIQUE MONTRÉAL | A Robotic Micro-assembly Process Inspired by the Construction of the Ancient Pyramids and Relying on Several Thousand of Flagellated Bacteria Acting as Workers
Oxygen-depleted hypoxic regions in the tumour are generally resistant to therapies. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour of magnetotactic bacteria, Magnetococcus marinus strain MC-1, can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals, tend to swim along local magnetic field lines and towards low oxygen concentrationsbased on a two-state aerotactic sensing system. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in severe combined immunodeficient beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.
Seth Rogen (Freaks and Geeks, Knocked Up, Superbad) and collaborator Evan Goldberg are writing the script for a pilot for a new “half-hour comedy television series about the Singularity for FX,” Rogen revealed Thursday (August 11) on Nerdist podcast: Seth Rogen Returns (at 55:20 mark), while promoting his latest film, Sausage Party (an animated movie that apparently sets a new world record for f-bombs, based on the trailer).
“Yeah, it’s happening, I just read an article about neural dust,” said host Chris Hardwick.
“Oh, it’s happening, it’s super scary, and we’re trying to make a comedy about it,” said Rogen. “We’ll film that in the next year, basically.”
“Neural dust are, like, small particles, kind of like nano-mites, that work in your systems,” Hardwick said, “and can …” — “wipe out whole civilizations,” Rogen interjected. “But, you know, they always kinda pitch you the good stuff first: it could help your body,” Hardwick added.
Also mentioned on the podcast: a “prank show [All People Are Famous] next week where the guy we’re pranking thinks he’s responsible for the Singularity … goes nuts, destroying everything. …”
A team of British and Chinese scientists has developed a new “metamaterial-based solid immersion lens” (mSIL) microscope lens design that can extend the magnification of an optical microscope to see objects smaller than the approximately 200 nanometers Abbe diffraction limit, the smallest size of bacteria.
Led by Zengbo Wang, PhD, at Bangor University UK and Prof Limin Wu at Fudan University, China, the team created minute droplet-like lens structures on the surface to be examined. These act as an additional lens to magnify the surface features previously invisible to a normal microscope lens, adding 5x magnification to existing microscopes.
Made of millions of nanobeads, the spheres break up the light beam. Acting as individual minute beams, each bead refracts the light. “We’ve used high-index titanium dioxide (TiO2) nanoparticles as the building element of the lens,” Wang says. “These nanoparticles are able to bend light to a higher degree than water.”
“Each sphere bends the light to a high magnitude and splits the light beam, creating millions of individual beams of light. It is these tiny light beams which enable us to view previously unseen detail.”
Wang believes that the results will be easily replicable and that other labs will soon be adopting the technology and using it for themselves. Titanium dioxide is cheap and readily available, so rather than buying a new microscope, the lenses are applied to the material to be viewed, rather than to the microscope.
“The next challenge is to adapt the technology for use in biology and medicine. This would not require the current use of a combination of dyes and stains and laser light, which change the samples being viewed,” he says.
The lens is described in a paper in the open-access journal Science Advances today (August 12).Abstract of Three-dimensional all-dielectric metamaterial solid immersion lens for subwavelength imaging at visible frequencies
Although all-dielectric metamaterials offer a low-loss alternative to current metal-based metamaterials to manipulate light at the nanoscale and may have important applications, very few have been reported to date owing to the current nanofabrication technologies. We develop a new “nano–solid-fluid assembly” method using 15-nm TiO2 nanoparticles as building blocks to fabricate the first three-dimensional (3D) all-dielectric metamaterial at visible frequencies. Because of its optical transparency, high refractive index, and deep-subwavelength structures, this 3D all-dielectric metamaterial-based solid immersion lens (mSIL) can produce a sharp image with a super-resolution of at least 45 nm under a white-light optical microscope, significantly exceeding the classical diffraction limit and previous near-field imaging techniques. Theoretical analysis reveals that electric field enhancement can be formed between contacting TiO2 nanoparticles, which causes effective confinement and propagation of visible light at the deep-subwavelength scale. This endows the mSIL with unusual abilities to illuminate object surfaces with large-area nanoscale near-field evanescent spots and to collect and convert the evanescent information into propagating waves. Our all-dielectric metamaterial design strategy demonstrates the potential to develop low-loss nanophotonic devices at visible frequencies.
Anti-inflammatory drug mefenamic acid completely reversed memory loss and brain inflammation in mice genetically engineered to develop symptoms of Alzheimer’s disease and amyloid beta-induced memory loss, a team led by David Brough, PhD, from the University of Manchester has discovered.
The non-steroidal anti-inflammatory drug (NSAID) drug targets an important inflammatory pathway called the NLRP3 inflammasome, which damages brain cells, according to Brough. This is the first time a drug has been shown to target this inflammatory pathway, highlighting its importance in the disease model, Brough said.
“Because this drug is already available and the toxicity and pharmacokinetics of the drug is known, the time for it to reach patients should, in theory, be shorter than if we were developing completely new drugs. We are now preparing applications to perform early phase II trials to determine a proof-of-concept that the molecules have an effect on neuroinflammation in humans.”
“There is experimental evidence now to strongly suggest that inflammation in the brain makes Alzheimer’s disease worse. Until now, no drug has been available to target this pathway, so we are very excited by this result.”
The research, funded by the Medical Research Council and the Alzheimer’s Society, paves the way for human trials that the team hopes to conduct in the future, but Brough cautions that more research is needed to identify its impact on humans and the long-term implications of its use.
The findings were published Thursday Aug. 11 in an open-access paper authored by Brough and colleagues in the journal Nature Communications.Abstract of Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes. The NLRP3 inflammasome is a multi-protein complex responsible for the processing of the proinflammatory cytokine interleukin-1β and is implicated in many inflammatory diseases. Here we show that several clinically approved and widely used NSAIDs of the fenamate class are effective and selective inhibitors of the NLRP3 inflammasome via inhibition of the volume-regulated anion channel in macrophages, independently of COX enzymes. Flufenamic acid and mefenamic acid are efficacious in NLRP3-dependent rodent models of inflammation in air pouch and peritoneum. We also show therapeutic effects of fenamates using a model of amyloid beta induced memory loss and a transgenic mouse model of Alzheimer’s disease. These data suggest that fenamate NSAIDs could be repurposed as NLRP3 inflammasome inhibitors and Alzheimer’s disease therapeutics.
A new way to send mechanical signals through soft robots and other autonomous soft systems has been developed by researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), in collaboration with colleagues at the California Institute of Technology, described in the journal Proceedings of the National Academy of Sciences.
Soft autonomous systems, just like the human body, can perform delicate movements that are safe for humans, unlike mechanical actuators controlled by wires. The problem is that in sending a mechanical signal through a soft material — to make a robot “muscle” move, for example — the signal becomes dissipated (weakened) and dispersed (scattered).
Think tapping on a solid wall to communicate via morse code with someone in the next room vs. tapping out a muffled message on a wall covered with thick, soft foam.
Transmitting signals through soft materials
The researchers solved this problem by using “bistable beams” (structures that function in two distinct states) to store and release elastic energy along the path of a wave.
This new system consists of a chain of bistable elastomeric (rubber-like) beam structures connected by elastomeric linear springs. When a beam is deformed (bent), it snaps and stores energy. As the signal travels along the elastomer, it snaps the beam back into place, releasing the beam’s stored energy and sending the signal downstream, like a line of dominos. This simple bistable system prevents the signal from dissipating downstream.
“This design solves two fundamental problems in transmitting information through materials,” said Katia Bertoldi, the John L. Loeb Associate Professor of the Natural Sciences at SEAS and senior author of the paper. “It not only overcomes dissipation, but it also eliminates dispersive [spreading out] effects, so that the signal propagates without distortion. As such, we maintain signal strength and clarity from start to end.” The team used advanced 3D printing techniques to fabricate the system.
Soft diodes and logic gates
The team also took the system a step further, designing and 3D-printing soft diodes and logic gates (a basic computational element that is normally part of a computer chip) using this same signal-transmission design. The gate can be controlled to act either as an AND (both inputs must be present to trigger the gate to fire) or as an OR gate (either one or both will trigger the gate to fire).
This research was supported by the National Science Foundation and the Harvard University Materials Research Science and Engineering Center (MRSEC).
Abstract of Stable propagation of mechanical signals in soft media using stored elastic energy
Soft structures with rationally designed architectures capable of large, nonlinear deformation present opportunities for unprecedented, highly-tunable devices and machines. However, the highly-dissipative nature of soft materials intrinsically limits or prevents certain functions, such as the propagation of mechanical signals. Here, we present an architected soft system comprised of elastomeric bistable beam elements connected by elastomeric linear springs. The dissipative nature of the polymer readily damps linear waves, preventing propagation of any mechanical signal beyond a short distance, as expected. However, the unique architecture of the system enables propagation of stable, nonlinear solitary transition waves with constant, controllable velocity and pulse geometry over arbitrary distances. Since the high damping of the material removes all other linear, small amplitude excitations, the desired pulse propagates with high delity and controllability. This phenomenon can be used to control signals, as demonstrated by the design of soft mechanical diodes and logic gates.
Imagine a soft liquid-metal material right out of the T-1000 Terminator movie character. One that can morph itself into different self-propelling soft electronic circuits that act like live cells, communicating with each other.
Using a liquid metallic core* and semiconducting skin, such a soft material might be used to make instant flexible 3D electronic displays. Or morph into self-propelled biomedical diagnostic sensors, for example, reconfiguring themselves on demand, say RMIT University researchers.
Morphing metal — more like live cells
To achieve that magic, Professor Kourosh Kalantar-zadeh and his group first immersed liquid-metal droplets in water. The droplets were able to move about freely in three dimensions, driven by pH (acid or base) or ionic (electric charge) concentration gradients across a liquid metal droplet, which induced deformation and surface flow.
“We adjusted the concentrations of acid, base, and salt components in the water and investigated the effect. Simply tweaking the water’s chemistry made the liquid metal droplets move and change shape, without any need for external mechanical, electronic, or optical stimulants.”
The elastic electronic soft circuit systems act more like live cells, moving around autonomously and communicating with each other to form new circuits, rather than being stuck in one configuration.
“Using this discovery, we were able to create moving objects, switches, and pumps that could operate autonomously — self-propelling liquid metals driven by the composition of the surrounding fluid,” Kalantar-zadeh said. “Eventually, using the fundamentals of this discovery, it may be possible to build a 3D liquid metal humanoid on demand.”
The research was published August 4 in open-access Nature Communications.
* Galinstan, an alloy of of 68.5% gallium, 21.5% indium, and 10% tin, is used as the model liquid metal. Galinstan’s melting point can be lowered to below 0 °C (32 °F).
Abstract of Ionic imbalance induced self-propulsion of liquid metals
RMIT University | Liquid metals propel future electronics | RMIT University
Components with self-propelling abilities are important building blocks of small autonomous systems and the characteristics of liquid metals are capable of fulfilling self-propulsion criteria. To date, there has been no exploration regarding the effect of electrolyte ionic content surrounding a liquid metal for symmetry breaking that generates motion. Here we show the controlled actuation of liquid metal droplets using only the ionic properties of the aqueous electrolyte. We demonstrate that pH or ionic concentration gradients across a liquid metal droplet induce both deformation and surface Marangoni flow. We show that the Lippmann dominated deformation results in maximum velocity for the self-propulsion of liquid metal droplets and illustrate several key applications, which take advantage of such electrolyte-induced motion. With this finding, it is possible to conceive the propulsion of small entities that are constructed and controlled entirely with fluids, progressing towards more advanced soft systems.
University of California, Berkeley engineers have designed and built millimeter-scale device wireless, batteryless “neural dust” sensors and implanted them in muscles and peripheral nerves of rats to make in vivo electrophysiological recordings.
The new technology opens the door to “electroceuticals” — bioelectronic methods to monitor and record wireless electromyogram (EMG) signals from muscle membranes and electroneurogram (ENG) signals from local neuron electrical activity, and to stimulate the immune system, reduce inflammation, and treat disorders such as epilepsy.
The technology could also improve neural control of prosthetics (allowing a paraplegic to control a computer or a robotic arm, for example) by stimulating nerves and muscles directly, instead of requiring implanted wires.
The neural-dust sensors use ultrasound technology to both power the sensors and read out measurements. Ultrasound is already well-developed for hospital use and can penetrate nearly anywhere in the body, unlike radio waves.
The researchers reported their findings August 3 in an open-access paper in the journal Neuron.
How a neural dust “mote” sensor monitors neural and muscle signals
1. A team implants the neural dust mote. In the reported study, the mote was implanted in the rat sciatic nerve to do ENG recordings and in the gastrocnemius muscle to do EMG recordings. The tether-less connection also avoids potential infections and adverse biological responses due to micro-motion of the implant within the tissue.
2. An external ultrasonic generator sends a ultrasound signal to a piezoelectric crystal, which converts the sound energy into an electrical voltage, used to power a transistor circuit — no battery required.
3. When neurons or muscle fibers fire, they generate a tiny voltage (action potential) that the two electrodes pick up and send to the transistor.
4. The transistor amplifies the signal and drives the piezoelectric crystal to vibrate at an ultrasonic rate.
5. That vibration interferes with the transmitted ultrasonic signal, causing a modified “backscatter” signal that communicates information about the voltage across the sensor’s two electrodes.
6. The backscatter ultrasound signal is decoded to extract EMG or ENG data.
7. A computer displays and records the information.
Microscale motes: future research
The experiments so far have involved the peripheral nervous system and muscles, using an external ultrasonic patch over the implanted site to acquire information from the motes for the desired diagnosis or therapy.
But according to the researchers, neural dust motes can be implanted anywhere in the body, including the central nervous system and brain to control prosthetics. This would be an alternative to today’s implantable electrodes (for Parkinson’s disease, for example), which require wires that pass through holes in the skull and degrade within one to two years.
The researchers are now building motes from biocompatible thin films, which would potentially last in the body without degradation for a decade or more. Up to hundreds of wireless sensors could be sealed in, avoiding infection and unwanted movement of the electrodes, and could last a timeline, according to the researchers.
The team is also now working to miniaturize the device further and they plan to use beam-steering technology to focus the ultrasonic signals on individual motes. The team is also building little backpacks for rats to hold the ultrasound transceiver that will record data from implanted motes. And the researchers are working to expand the motes’ ability to detect non-electrical signals, such as oxygen or hormone levels.
The researchers estimate that they could eventually shrink the sensors down to a cube 50 micrometers on a side. At that size, the motes could monitor a few specific nerve axons and continually record their electrical activity.
The researchers conceived of the idea of neural dust about five years ago, but initial attempts to power an implantable device and read out the data using radio waves were disappointing. Radio attenuates very quickly with distance in tissue, so communicating with devices deep in the body would be difficult without using potentially damaging high-intensity radiation. In 2013, the researchers published an open-access arXiv paper that described how a neural-dust system with ultrasonic signals might work.
The ongoing research is supported by the U.S. Defense Advanced Research Projects Agency as part of DARPA’s Electrical Prescriptions (ElectRx) program, which is focused in part on developing interface technologies that are suitable for chronic use for biosensing and neuromodulation of specific peripheral nerves.
UC Berkeley | “Neural dust” sensor
Abstract of Wireless Recording in the Peripheral Nervous System with Ultrasonic Neural Dust
The emerging field of bioelectronic medicine seeks methods for deciphering and modulating electrophysiological activity in the body to attain therapeutic effects at target organs. Current approaches to interfacing with peripheral nerves and muscles rely heavily on wires, creating problems for chronic use, while emerging wireless approaches lack the size scalability necessary to interrogate small-diameter nerves. Furthermore, conventional electrode-based technologies lack the capability to record from nerves with high spatial resolution or to record independently from many discrete sites within a nerve bundle. Here, we demonstrate neural dust, a wireless and scalable ultrasonic backscatter system for powering and communicating with implanted bioelectronics. We show that ultrasound is effective at delivering power to mm-scale devices in tissue; likewise, passive, battery-less communication using backscatter enables high-fidelity transmission of electromyogram (EMG) and electroneurogram (ENG) signals from anesthetized rats. These results highlight the potential for an ultrasound-based neural interface system for advancing future bioelectronics-based therapies.
A week ago on KurzweilAI, we learned that prolonged sitting may increase risk of death, but that an hour of moderate exercise a day is enough to counter health risks. Now new research suggests that such exercise results in larger brain size and lowered dementia risk, while other new research suggests that the new neurons created in that exercise preserve old memories, contrary to previous research.
Exercise results in larger brain size and lowered dementia risk
UCLA researchers have found an association between low physical activity and a higher risk for dementia in older individuals, based on data from the landmark Framingham Heart Study.
The researchers found that physical activity particularly affected the size of the hippocampus, involved in short-term memory. They also found the protective effect of regular physical activity against dementia was strongest in people age 75 and older.
This suggests that regular physical activity for older adults could lead to higher brain volumes and a reduced risk for developing dementia.
The Framingham study was begun in 1948 primarily as a way to trace factors and characteristics leading to cardiovascular disease, but also examining dementia and other physiological conditions. For this study, the UCLA researchers followed an older, community-based cohort from the Framingham study for more than a decade to examine the association between physical activity and the risk for incident dementia and subclinical brain MRI markers of dementia.
The study appears in the Journals of Gerontology Series A: Biological Sciences and Medical Sciences. It was supported by an NIH/National Heart, Lung, and Blood Institute contract and training grant, the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, and the American Heart Association.
New neurons created through exercise don’t cause you to forget old memories
Meanwhile, Texas A&M College of Medicine scientists have found in a study recently published in the Journal of Neuroscience that exercise causes more new neurons to be formed in a critical brain region — and contrary to an earlier study, these new neurons do not cause the individual to forget old memories.
Exercise is well known for its cognitive benefits, thought to occur because it causes neurogenesis, or the creation of new neurons, in the hippocampus, which is a key brain region for learning, memory and mood regulation. So it was a surprise in 2014 when a research study, published in the journal Science, found that exercise caused mice to forget what they’d already learned.
“It stunned the field of hippocampal neurogenesis,” said Ashok K. Shetty, PhD, a professor in the Texas A&M College of Medicine Department of Molecular and Cellular Medicine, associate director of the Institute for Regenerative Medicine, and research career scientist at the Central Texas Veterans Health Care System.
The animal models in the exercise group — in the previous study — showed far more neurogenesis than the control group, but these additional neurons seemed to erase memories that were formed before they started the exercise regimen. To test this, the researchers removed the extra neurons, and the mice suddenly were able to remember again.
Replicating the research with rats reversed the outcome
Shetty and his team decided to replicate this earlier research, using rats instead of mice. Rats are thought to be more like humans physiologically, with more-similar neuronal workings. They found that these animal models showed no such degradation in memories.
The researchers trained their animal models to complete a task over the course of four days, followed by several days of memory consolidation by performing the task over and over again. Then, half the trained animal models were put into cages with running wheels for several weeks, while the control group remained sedentary.
The rats who ran further over the course of that time had much greater neurogenesis in their hippocampus, and all rats who had access to a wheel (and therefore ran at least some), had greater neurogenesis than the sedentary group.
Importantly, despite differing levels of increased neurogenesis, both moderate runners and brisk runners (those who ran further than average) in Shetty’s study showed the same ability as the sedentary runners to recall the task they learned before they began to exercise.
This means even a large amount of running (akin to people who perform significant amount of exercise on a daily basis) doesn’t interfere with the recall of memory.
Why fidgeting can protect leg arteries and improve learning
But not everybody has that extra hour — or is motivated to exercise. For all of us couch/desk-bound folks, new research suggests a simple sitting exercise that may tide you over until you can go for a walk or run: fidgeting.
Ignore that teacher advice to “sit in your seat and don’t fidget!” — which the National Education Association says in this article actually improves learning — and suggests footrests using old tires to make giant rubber bands to facilitate fidgeting.
University of Missouri researchers have found that fidgeting while sitting can also protect the arteries in legs and potentially help prevent the arterial disease that may be brought on by binge TV watching or working at a computer.
In the study, the researchers compared the leg vascular function of 11 healthy young men and women before and after three hours of sitting. While sitting, the participants were asked to fidget one leg intermittently, tapping one foot for one minute and then resting it for four minutes, while the other leg remained still throughout. On average, the participants moved their feet 250 times per minute.
The researchers then measured the blood flow of the popliteal — an artery in the lower leg — and found that the fidgeting leg had a significant increase in blood flow, as expected, while the stationary leg experienced a reduction in blood flow.
Research has shown that increased blood flow and its associated shear stress — the friction of the flowing blood on the artery wall — is an important stimulus for vascular health.
While only one leg was exposed to fidgeting during the experiment, in a real-world scenario the researchers recommend tapping both legs to maximize the beneficial effects.
But not a substitute for walking and exercise
“Many of us sit for hours at a time, whether it’s binge watching our favorite TV show or working at a computer,” said Jaume Padilla, PhD, an assistant professor of nutrition and exercise physiology at MU and lead author of the study.
“We wanted to know whether a small amount of leg fidgeting could prevent a decline in leg vascular function caused by prolonged sitting. While we expected fidgeting to increase blood flow to the lower limbs, we were quite surprised to find this would be sufficient to prevent a decline in arterial function.”
But fidgeting is not a substitute for walking and exercise, which produce more overall cardiovascular benefits, the researchers caution.
“You should attempt to break up sitting time as much as possible by standing or walking,” Padilla said. “But if you’re stuck in a situation in which walking just isn’t an option, fidgeting can be a good alternative. Any movement is better than no movement.”
The study was recently published in the American Journal of Physiology Heart and Circulatory Physiology and was supported by the NIH and the Japan Society for the Promotion of Science.
Abstract of Physical Activity, Brain Volume, and Dementia Risk: The Framingham Study
Background: Several longitudinal studies found an inverse relationship between levels of physical activity and cognitive decline, dementia, and/or Alzheimer’s disease (AD), but results have been inconsistent. We followed an older, community-based cohort for over a decade to examine the association of physical activity with the risk of incident dementia and subclinical brain MRI markers of dementia.
Methods: The physical activity index (PAI) was assessed in the Framingham Study Original and Offspring cohorts, aged 60 years or older. We examined the association between PAI and risk of incident all-cause dementia and AD in participants of both cohorts who were cognitively intact and had available PAI (n = 3,714; 54% women; mean age = 70±7 years). We additionally examined the association between PAI and brain MRI in the Offspring cohort (n = 1,987).
Results: Over a decade of follow-up, 236 participants developed dementia (188 AD). Participants in the lowest quintile of PAI had an increased risk of incident dementia compared with those in higher quintiles (hazard ratio [HR] = 1.50, 95% confidence interval [CI] = 1.04–1.97, p = .028) in a multivariable-adjusted model. Secondary analysis revealed that this relation was limited to participants who were apolipoprotein (APO)E ε4 allele noncarriers (HR = 1.58, 95% CI = 1.08–2.32; p = .018) and strongest in participants aged 75 years or older. PAI was also linearly related to total brain and hippocampal volumes (β ± SE = 0.24±0.06; p < .01 and 0.004±0.001; p = .003, respectively).
Conclusion: Low physical activity is associated with a higher risk for dementia in older individuals, suggesting that a reduced risk of dementia and higher brain volumes may be additional health benefits of maintaining physical activity into old age.
Abstract of Voluntary Running Exercise-Mediated Enhanced Neurogenesis Does Not Obliterate Retrograde Spatial Memory
Running exercise (RE) improves cognition, formation of anterograde memories, and mood, alongside enhancing hippocampal neurogenesis. A previous investigation in a mouse model showed that RE-induced increased neurogenesis erases retrograde memory (Akers et al., 2014). However, it is unknown whether RE-induced forgetting is common to all species. We ascertained whether voluntary RE-induced enhanced neurogenesis interferes with the recall of spatial memory in rats. Young rats assigned to either sedentary (SED) or running exercise (RE) groups were first subjected to eight learning sessions in a water maze. A probe test (PT) conducted 24 h after the final training session confirmed that animals in either group had a similar ability for the recall of short-term memory. Following this, rats in the RE group were housed in larger cages fitted with running wheels, whereas rats in the SED group remained in standard cages. Animals in the RE group ran an average of 78 km in 4 weeks. A second PT performed 4 weeks after the first PT revealed comparable ability for memory recall between animals in the RE and SED groups, which was evidenced through multiple measures of memory retrieval function. The RE group displayed a 1.5- to 2.1-fold higher hippocampal neurogenesis than SED rats. Additionally, both moderate and brisk RE did not interfere with the recall of memory, although increasing amounts of RE proportionally enhanced neurogenesis. In conclusion, RE does not impair memory recall ability in a rat model despite substantially increasing neurogenesis.
SIGNIFICANCE STATEMENT Running exercise (RE) improves new memory formation along with an increased neurogenesis in the hippocampus. In view of a recent study showing that RE-mediated increased hippocampal neurogenesis promotes forgetfulness in a mouse model, we ascertained whether a similar adverse phenomenon exists in a rat model. Memory recall ability examined 4 weeks after learning confirmed that animals that had run a mean of 78 km and displayed a 1.5- to 2.1-fold increase in hippocampal neurogenesis demonstrated similar proficiency for memory recall as animals that had remained sedentary. Furthermore, both moderate and brisk RE did not interfere with memory recall, although increasing amounts of RE proportionally enhanced neurogenesis, implying that RE has no adverse effects on memory recall.
Abstract of Prolonged sitting-induced leg endothelial dysfunction is prevented by fidgeting
Prolonged sitting impairs endothelial function in the leg vasculature, and this impairment is thought to be largely mediated by a sustained reduction in blood flow-induced shear stress. Indeed, preventing the marked reduction of shear stress during sitting with local heating abolishes the impairment in popliteal artery endothelial function. Herein, we tested the hypothesis that sitting-induced reductions in shear stress and ensuing endothelial dysfunction would be prevented by periodic leg movement, or “fidgeting.” In 11 young, healthy subjects, bilateral measurements of popliteal artery flow-mediated dilation (FMD) were performed before and after a 3-h sitting period during which one leg was subjected to intermittent fidgeting (1 min on/4 min off) while the contralateral leg remained still throughout and served as an internal control. Fidgeting produced a pronounced increase in popliteal artery blood flow and shear rate (prefidgeting, 33.7 ± 2.6 s−1 to immediately postfidgeting, 222.7 ± 28.3 s−1; mean ± SE; P < 0.001) that tapered off during the following 60 s. Fidgeting did not alter popliteal artery blood flow and shear rate of the contralateral leg, which was subjected to a reduction in blood flow and shear rate throughout the sitting period (presit, 71.7 ± 8.0 s−1 to 3-h sit, 20.2 ± 2.9 s−1; P < 0.001). Popliteal artery FMD was impaired after 3 h of sitting in the control leg (presit, 4.5 ± 0.3% to postsit: 1.6 ± 1.1%; P = 0.039) but improved in the fidgeting leg (presit, 3.7 ± 0.6% to postsit, 6.6 ± 1.2%; P = 0.014). Collectively, the present study provides evidence that prolonged sitting-induced leg endothelial dysfunction is preventable with small amounts of leg movement while sitting, likely through the intermittent increases in vascular shear stress.
Scientists at IBM Research in Zurich have developed artificial neurons that emulate how neurons spike (fire). The goal is to create energy-efficient, high-speed, ultra-dense integrated neuromorphic (brain-like) technologies for applications in cognitive computing, such as unsupervised learning for detecting and analyzing patterns.
Applications could include internet of things sensors that collect and analyze volumes of weather data for faster forecasts and detecting patterns in financial transactions, for example.
The results of this research appeared today (Aug. 3) as a cover story in the journal Nature Nanotechnology.
Emulating neuron spiking
IBM’s new neuron-like spiking mechanism is based on a recent IBM breakthrough in phase-change materials. Phase-change materials are used for storing and processing digital data in re-writable Blu-ray discs, for example. The new phase-change materials developed by IBM recently are used instead for storing and processing analog data — like the synapses and neurons in our biological brains.
The new phase-change materials also overcome problems in conventional computing, where there’s a separate memory and logic unit, slowing down computation. These functions are combined in the new artificial neurons, just as they are in a biological neuron.
Alternative to von-Neumann-based algorithms
In addition, previous attempts to build artificial neurons are built using CMOS-based circuits, the standard transistor technology we have in our computers. The new phase-change technology can reproduce similar functionality at reduced power consumption. The artificial neurons are also superior in functioning at nanometer-length-scale dimensions and feature native stochasticity (based on random variables, simulating neurons).
“Populations of stochastic phase-change neurons, combined with other nanoscale computational elements such as artificial synapses, could be a key enabler for the creation of a new generation of extremely dense neuromorphic computing systems,” said Tomas Tuma, a co-author of the paper.
“The relatively complex computational tasks, such as Bayesian inference, that stochastic neuronal populations can perform with collocated processing and storage render them attractive as a possible alternative to von-Neumann-based algorithms in future cognitive computers,” the IBM scientists state in the paper.
IBM scientists have organized hundreds of these artificial neurons into populations and used them to represent fast and complex signals. These artificial neurons have been shown to sustain billions of switching cycles, which would correspond to multiple years of operation at an update frequency of 100 Hz. The energy required for each neuron update was less than five picojoule and the average power less than 120 microwatts — for comparison, 60 million microwatts power a 60 watt lightbulb.
IBM Research | All-memristive neuromorphic computing with level-tuned neurons
Abstract of Stochastic phase-change neurons
Artificial neuromorphic systems based on populations of spiking neurons are an indispensable tool in understanding the human brain and in constructing neuromimetic computational systems. To reach areal and power efficiencies comparable to those seen in biological systems, electroionics-based and phase-change-based memristive devices have been explored as nanoscale counterparts of synapses. However, progress on scalable realizations of neurons has so far been limited. Here, we show that chalcogenide-based phase-change materials can be used to create an artificial neuron in which the membrane potential is represented by the phase configuration of the nanoscale phase-change device. By exploiting the physics of reversible amorphous-to-crystal phase transitions, we show that the temporal integration of postsynaptic potentials can be achieved on a nanosecond timescale. Moreover, we show that this is inherently stochastic because of the melt-quench-induced reconfiguration of the atomic structure occurring when the neuron is reset. We demonstrate the use of these phase-change neurons, and their populations, in the detection of temporal correlations in parallel data streams and in sub-Nyquist representation of high-bandwidth signals.
Eating more protein from plant sources was associated with a lower risk of death, while eating more protein from animals was associated with a higher risk of death — especially among adults with at least one unhealthy behavior such as smoking, drinking, and being overweight or sedentary — according to an open-access survey article published online by JAMA Internal Medicine.
Mingyang Song, M.D., Sc.D., of Massachusetts General Hospital and Harvard Medical School, and coauthors used data from two large U.S. studies, with repeated measures of diet through food questionnaires and up to 32 years of follow-up of 131,342 participants.
The authors report:
- After adjusting for major lifestyle and dietary risk factors, every 10 percent increment of animal protein from total calories was associated with a 2 percent higher risk of death from all causes and an 8 percent increased risk of death from cardiovascular disease death.
- In contrast, eating more plant protein was associated with a 10 percent lower risk of death from all causes for every 3 percent increment of total calories and a 12 percent lower risk of cardiovascular death.
- Increased mortality associated with eating more animal protein was more pronounced among study participants who were obese and those who drank alcohol heavily.
- The association between eating more plant protein and lower mortality was stronger among study participants who smoked, drank at least 14 grams of alcohol a day, were overweight or obese, were physically inactive or were younger than 65 or older than 80.
- Substituting 3 percent of calories from animal protein with plant protein was associated with a lower risk of death from all causes: 34 percent for replacing processed red meat, 12 percent for replacing unprocessed red meat and 19 percent for replacing eggs.
“Substitution of plant protein for animal protein, especially from processed red meat, may confer substantial health benefit. Therefore, public health recommendations should focus on improvement of protein sources,” the study concludes.
Limitations of the study
Limitations include the study’s observational design, so residual confounding (other mitigating factors) cannot be excluded, and “the moderately higher protein consumption (median, 19% of calories) in our study population compared with the general U.S. population (15%-16%), thus limiting our ability to assess the effect of the very low end of intake,” the authors note. “Other components in protein-rich foods (e.g., sodium,nitrates, and nitrites in processed red meat), in addition to protein per se, may have a critical health effect.”
Some nutritionists also advise that deficiencies in the diet of vegetarians may include vitamin B(12), vitamin D, omega-3 fatty acids, calcium, iron, and zinc, which may require supplements and fortified foods, according to a 2010 analysis in the journal Nutrition in Clinical Practice.
* They examined hazard ratios (risk) for all-cause and cause-specific mortality in relation to eating animal protein vs. plant protein. Median protein intake, measured as a percentage of calories, was 14 percent for animal protein and 4 percent for plant protein. Among 131,342 study participants, 85,013 (64.7 percent) were women and the average age of participants was 49.
Abstract of Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality
Importance Defining what represents a macronutritionally balanced diet remains an open question and a high priority in nutrition research. Although the amount of protein may have specific effects, from a broader dietary perspective, the choice of protein sources will inevitably influence other components of diet and may be a critical determinant for the health outcome.
Objective To examine the associations of animal and plant protein intake with the risk for mortality.
Design, Setting, and Participants This prospective cohort study of US health care professionals included 131 342 participants from the Nurses’ Health Study (1980 to end of follow-up on June 1, 2012) and Health Professionals Follow-up Study (1986 to end of follow-up on January 31, 2012). Animal and plant protein intake was assessed by regularly updated validated food frequency questionnaires. Data were analyzed from June 20, 2014, to January 18, 2016.
Main Outcomes and Measures Hazard ratios (HRs) for all-cause and cause-specific mortality.
Results Of the 131 342 participants, 85 013 were women (64.7%) and 46 329 were men (35.3%) (mean [SD] age, 49  years). The median protein intake, as assessed by percentage of energy, was 14% for animal protein (5th-95th percentile, 9%-22%) and 4% for plant protein (5th-95th percentile, 2%-6%). After adjusting for major lifestyle and dietary risk factors, animal protein intake was weakly associated with higher mortality, particularly cardiovascular mortality (HR, 1.08 per 10% energy increment; 95% CI, 1.01-1.16; P for trend = .04), whereas plant protein was associated with lower mortality (HR, 0.90 per 3% energy increment; 95% CI, 0.86-0.95; P for trend < .001). These associations were confined to participants with at least 1 unhealthy lifestyle factor based on smoking, heavy alcohol intake, overweight or obesity, and physical inactivity, but not evident among those without any of these risk factors. Replacing animal protein of various origins with plant protein was associated with lower mortality. In particular, the HRs for all-cause mortality were 0.66 (95% CI, 0.59-0.75) when 3% of energy from plant protein was substituted for an equivalent amount of protein from processed red meat, 0.88 (95% CI, 0.84-0.92) from unprocessed red meat, and 0.81 (95% CI, 0.75-0.88) from egg.
Conclusions and Relevance High animal protein intake was positively associated with mortality and high plant protein intake was inversely associated with mortality, especially among individuals with at least 1 lifestyle risk factor. Substitution of plant protein for animal protein, especially that from processed red meat, was associated with lower mortality, suggesting the importance of protein source.
For medics on the battlefield and doctors in remote or developing parts of the world, getting rapid access to the drugs needed to treat patients can be challenging. That’s because biopharmaceutical drugs, which are used in a wide range of therapies including vaccines and treatments for diabetes and cancer, are currently produced in large, centralized fermentation plants. Then they must be transported to the treatment site, which can be expensive, time-consuming, and difficult to execute in areas with poor supply chains.
In an open-access paper published Friday July 29 in the journal Nature Communications, the researchers demonstrate that the system can be used to produce a single dose of treatment from a compact device containing just a small droplet of cells in a liquid.
The system could ultimately be carried onto the battlefield and used to produce treatments at the point of care. It could also be used to manufacture a vaccine to prevent a disease outbreak in a remote village, according to senior author Tim Lu, an associate professor of biological engineering and electrical engineering and computer science, and head of the Synthetic Biology Group at MIT’s Research Laboratory of Electronics. “Imagine you were on Mars or in a remote desert, without access to a full formulary; you could program the yeast to produce drugs on demand locally,” Lu says.
The prototype system is based on a programmable strain of yeast, Pichia pastoris, which can be induced to express (generate) one of two therapeutic proteins when exposed to a particular chemical trigger. The researchers chose P. pastoris because it can grow to very high densities on simple and inexpensive carbon sources, and is able to express large amounts of protein. “We altered the yeast so it could be more easily genetically modified, and could include more than one therapeutic in its repertoire,” Lu says.
In an experiment, when the researchers exposed the modified yeast to estrogen β-estradiol, the cells expressed recombinant human growth hormone (rHGH). But when they exposed the same cells to methanol, the yeast expressed the protein interferon.
How to create a DIY biopharmaceutical drug
- Put the yeast cells into the millimeter-scale table-top microbioreactor.
- Feed a liquid containing the desired chemical trigger (such as methanol) into the reactor to mix with the cells.
- Gently massage the liquid droplet to ensure its contents are fully mixed together.
- Pressurize the gas in the reactor. That causes oxygen to flow through a silicone rubber membrane and allows carbon dioxide to be extracted.
- The device continuously monitors conditions within microfluidic chip, including monitors cell density, oxygen levels, temperature, and pH, to ensure the optimum environment for cell growth.
- If you need a different protein, just flush the liquid through a filter, leaving the cells behind*. Then add fresh liquid containing a new chemical trigger to stimulate production of the next protein.
The researchers are now investigating how to use the system in combinatorial treatments, in which multiple therapeutics, such as antibodies, are used together. Combining multiple therapeutics in this way can be expensive if each requires its own production line, Lu says. “But if you could engineer a single strain, or maybe even a consortia of strains that grow together, to manufacture combinations of biologics or antibodies, that could be a very powerful way of producing these drugs at a reasonable cost,” he says.
* Other research teams have previously attempted to build microbioreactors, but these could not retain the protein-producing cells while flushing out the liquid they are mixed with.
Current biopharmaceutical manufacturing systems are not compatible with portable or distributed production of biologics, as they typically require the development of single biologic-producing cell lines followed by their cultivation at very large scales. Therefore, it remains challenging to treat patients in short time frames, especially in remote locations with limited infrastructure. To overcome these barriers, we developed a platform using genetically engineered Pichia pastoris strains designed to secrete multiple proteins on programmable cues in an integrated, benchtop, millilitre-scale microfluidic device. We use this platform for rapid and switchable production of two biologics from a single yeast strain as specified by the operator. Our results demonstrate selectable and near-single-dose production of these biologics in <24 h with limited infrastructure requirements. We envision that combining this system with analytical, purification and polishing technologies could lead to a small-scale, portable and fully integrated personal biomanufacturing platform that could advance disease treatment at point-of-care.
A new study of human intelligence by University of Warwick researchers and associates at nine universities in China and NEC Laboratories America has quantified the brain’s dynamic functions, identifying how different parts of the brain interact with each other at different times, they reported in the journal Brain.
The more variable a brain is, and the more its different parts frequently connect with each other, the higher a person’s intelligence and creativity are, the researchers found .
Specifically, using resting-state MRI analysis of 1180 people’s brains in eight datasets around the world, the researchers discovered that the areas of the brain associated with learning and development, such as the hippocampus, show high levels of temporal variability — meaning that they change their neural connections with other parts of the brain more frequently, over a matter of minutes or seconds. But regions of the brain that aren’t associated with intelligence — visual, auditory, and sensory-motor areas — show small variability and adaptability.
This more accurate understanding of human intelligence could be applied to the construction of advanced artificial neural networks for computers, with the ability to learn, grow and adapt, the researchers suggest. Currently, AI systems do not process the functional variability and adaptability that is vital to the human brain for growth and learning, they note.
Improving mental-health treatments
This study may also have implications for a deeper understanding of another largely misunderstood field: mental health. Altered patterns of variability were observed in the brain’s default network with schizophrenia, autism, and attention deficit hyperactivity disorder (ADHD) patients.
Knowing the root cause of mental-health defects may bring scientists closer to treating and preventing these conditions in the future, according to the researchers.
Abstract of Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders
Functional brain networks demonstrate significant temporal variability and dynamic reconfiguration even in the resting state. Currently, most studies investigate temporal variability of brain networks at the scale of single (micro) or whole-brain (macro) connectivity. However, the mechanism underlying time-varying properties remains unclear, as the coupling between brain network variability and neural activity is not readily apparent when analysed at either micro or macroscales. We propose an intermediate (meso) scale analysis and characterize temporal variability of the functional architecture associated with a particular region. This yields a topography of variability that reflects the whole-brain and, most importantly, creates an analytical framework to establish the fundamental relationship between variability of regional functional architecture and its neural activity or structural connectivity. We find that temporal variability reflects the dynamical reconfiguration of a brain region into distinct functional modules at different times and may be indicative of brain flexibility and adaptability. Primary and unimodal sensory-motor cortices demonstrate low temporal variability, while transmodal areas, including heteromodal association areas and limbic system, demonstrate the high variability. In particular, regions with highest variability such as hippocampus/parahippocampus, inferior and middle temporal gyrus, olfactory gyrus and caudate are all related to learning, suggesting that the temporal variability may indicate the level of brain adaptability. With simultaneously recorded electroencephalography/functional magnetic resonance imaging and functional magnetic resonance imaging/diffusion tensor imaging data, we also find that variability of regional functional architecture is modulated by local blood oxygen level-dependent activity and α-band oscillation, and is governed by the ratio of intra- to inter-community structural connectivity. Application of the mesoscale variability measure to multicentre datasets of three mental disorders and matched controls involving 1180 subjects reveals that those regions demonstrating extreme, i.e. highest/lowest variability in controls are most liable to change in mental disorders. Specifically, we draw attention to the identification of diametrically opposing patterns of variability changes between schizophrenia and attention deficit hyperactivity disorder/autism. Regions of the default-mode network demonstrate lower variability in patients with schizophrenia, but high variability in patients with autism/attention deficit hyperactivity disorder, compared with respective controls. In contrast, subcortical regions, especially the thalamus, show higher variability in schizophrenia patients, but lower variability in patients with attention deficit hyperactivity disorder. The changes in variability of these regions are also closely related to symptom scores. Our work provides insights into the dynamic organization of the resting brain and how it changes in brain disorders. The nodal variability measure may also be potentially useful as a predictor for learning and neural rehabilitation.
American Heart Association | Signs and Symptoms of VTE
Prolonged sitting, such as watching a lot of television every day, may increase your risk of dying from a blood clot in the lung, according to a new open-access research letter published July 26 in the American Heart Association’s journal Circulation.
A lung blood clot (pulmonary embolism) usually begins as a clot in the leg or pelvis as a result of inactivity and slowed blood flow (deep vein thrombosis). If the clot breaks free, it can travel to a lung and become lodged in a small blood vessel, where it is especially dangerous.
From 1988 to 1990, Japanese researchers asked 86,024 participants, age 40-79, how many hours they spent watching TV. Over the next 19 years, 59 participants died of a pulmonary embolism*.
The researchers found that compared to participants who watched TV less than 2.5 hours each day, deaths from a pulmonary embolism increased by 70 percent among those who watched TV from 2.5 to 4.9 hours; by 40 percent for each additional 2 hours of daily TV watching; and 2.5 times among those who watched TV 5 or more hours.
“Pulmonary embolism occurs at a lower rate in Japan than it does in Western countries, but it may be on the rise,” said Hiroyasu Iso, M.D., Ph.D., professor of public health at Osaka University Graduate School of Medicine and study corresponding author. “The Japanese people are increasingly adopting sedentary lifestyles, which we believe is putting them at increased risk.”
Authors noted that the risk is likely greater than the findings suggest. Deaths from pulmonary embolism are believed to be underreported because diagnosis is difficult. The most common symptoms of pulmonary embolism — chest pain and shortness of breath — are the same as other life-threatening conditions, and diagnosis requires imaging that many hospitals are not equipped to provide.
Other risks factors studied were obesity (the strongest link after hours sitting), diabetes, cigarette smoking, and hypertension.
The researchers said the findings may be particularly relevant to Americans, since U.S. adults watch more television — especially “binge watching” — than Japanese adults (according to another study).
The researchers advised a few simple steps to avoid a pulmonary embolism: “After an hour or so, stand up, stretch, walk around, or while you’re watching TV, tense and relax your leg muscles for 5 minutes (similar to that given to travelers on long plane flights), keep hydrated, and shed pounds if overweight.
An hour of moderate exercise a day enough to counter health risks from prolonged sitting
University of Cambridge researchers, in another new study published July 27 in Lancet, noted that recent estimates suggest that more than 5 million people die globally each year as a result of failing to meet recommended daily activity levels.
But they found that 60 to 75 minutes of moderate intensity exercise per day were sufficient to eliminate the increased risk of early death associated with sitting for over eight hours per day, based on an analysis of 16 studies, which included data from more than one million men and women.** (Three out of four people in the study failed to reach this level of daily activity, though.)
The greatest risk of early death was for those individuals who were physically inactive. They were between 28% and 59% more likely to die early compared with those who were in the most active quartile — a risk similar to that associated with smoking and obesity. In other words, lack of physical activity is a greater health risk than prolonged sitting.
The enormous economic burden of physical inactivity — a global pandemic
Another study, also published July 27 in Lancet, revealed that in 2013, physical inactivity cost INT $67.5 billion*** (in international dollars = what U.S. dollars could buy in 2013) globally in healthcare expenditure and lost productivity in 142 countries, representing 93.2 per cent of the world’s population. The study was based on the direct health-care cost, productivity losses, and disability-adjusted life years (DALYs) for five major non-communicable diseases attributable to inactivity: coronary heart disease, stroke, type 2 diabetes, breast cancer and colon cancer.
* The study, which is part of the Japan Collaborative Cohort Study funded by the Ministry of Education, Science, Sports and Culture of Japan, was conducted before computers, tablets and smartphones became popular sources of information and entertainment. The researchers believe new studies are needed to determine the effect of these new technologies on pulmonary embolism risk.
** The researchers acknowledge that there are limitations to the data analyzed, which mainly came from participants aged 45 years and older and living in western Europe, the U.S. and Australia. But the researchers asked all included studies to reanalyze their data in a harmonized manner, an approach that has never before been adopted for a study of this size and therefore also provides much more robust effect estimates compared with previous studies.
*** Cost breakdown:
$67.5bn: Total costs, including $53.8bn in direct cost (healthcare expenditure) and 13.7bn in indirect costs (productivity losses).
$31.2bn: Total loss in tax revenue through public healthcare expenditure
$12.9bn: Total amount in private sector pays for physical inactivity-related diseases (e.g. health insurance companies)
$9.7bn: Total amount households paid out-of-pocket for physical inactivity-related diseases
Type 2 Diabetes was the costliest disease, accounting for $37.6bn (70 percent) of direct costs.
Abstract of Watching Television and Risk of Mortality From Pulmonary Embolism Among Japanese Men and Women
Although case series reporting pulmonary embolism or deep vein thrombosis after prolonged television watching have been published, no prospective study has examined the association between time spent watching television and the risk of mortality from pulmonary embolism. We examined this association in a large cohort study of Japanese men and women.
Abstract of Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women
Background: High amounts of sedentary behaviour have been associated with increased risks of several chronic conditions and mortality. However, it is unclear whether physical activity attenuates or even eliminates the detrimental effects of prolonged sitting. We examined the associations of sedentary behaviour and physical activity with all-cause mortality.
Methods: We did a systematic review, searching six databases (PubMed, PsycINFO, Embase, Web of Science, Sport Discus, and Scopus) from database inception until October, 2015, for prospective cohort studies that had individual level exposure and outcome data, provided data on both daily sitting or TV-viewing time and physical activity, and reported effect estimates for all-cause mortality, cardiovascular disease mortality, or breast, colon, and colorectal cancer mortality. We included data from 16 studies, of which 14 were identified through a systematic review and two were additional unpublished studies where pertinent data were available. All study data were analysed according to a harmonised protocol, which categorised reported daily sitting time and TV-viewing time into four standardised groups each, and physical activity into quartiles (in metabolic equivalent of task [MET]-hours per week). We then combined data across all studies to analyse the association of daily sitting time and physical activity with all-cause mortality, and estimated summary hazard ratios using Cox regression. We repeated these analyses using TV-viewing time instead of daily sitting time.
Findings: Of the 16 studies included in the meta-analysis, 13 studies provided data on sitting time and all-cause mortality. These studies included 1 005 791 individuals who were followed up for 2–18·1 years, during which 84 609 (8·4%) died. Compared with the referent group (ie, those sitting <4 h/day and in the most active quartile [>35·5 MET-h per week]), mortality rates during follow-up were 12–59% higher in the two lowest quartiles of physical activity (from HR=1·12, 95% CI 1·08–1·16, for the second lowest quartile of physical activity [<16 MET-h per week] and sitting <4 h/day; to HR=1·59, 1·52–1·66, for the lowest quartile of physical activity [<2·5 MET-h per week] and sitting >8 h/day). Daily sitting time was not associated with increased all-cause mortality in those in the most active quartile of physical activity. Compared with the referent (<4 h of sitting per day and highest quartile of physical activity [>35·5 MET-h per week]), there was no increased risk of mortality during follow-up in those who sat for more than 8 h/day but who also reported >35·5 MET-h per week of activity (HR=1·04; 95% CI 0·99–1·10). By contrast, those who sat the least (<4 h/day) and were in the lowest activity quartile (<2·5 MET-h per week) had a significantly increased risk of dying during follow-up (HR=1·27, 95% CI 1·22–1·31). Six studies had data on TV-viewing time (N=465 450; 43 740 deaths). Watching TV for 3 h or more per day was associated with increased mortality regardless of physical activity, except in the most active quartile, where mortality was significantly increased only in people who watched TV for 5 h/day or more (HR=1·16, 1·05–1·28).
Interpretation: High levels of moderate intensity physical activity (ie, about 60–75 min per day) seem to eliminate the increased risk of death associated with high sitting time. However, this high activity level attenuates, but does not eliminate the increased risk associated with high TV-viewing time. These results provide further evidence on the benefits of physical activity, particularly in societies where increasing numbers of people have to sit for long hours for work and may also inform future public health recommendations.
Abstract of The economic burden of physical inactivity: a global analysis of major non-communicable diseases
Background: The pandemic of physical inactivity is associated with a range of chronic diseases and early deaths. Despite the well documented disease burden, the economic burden of physical inactivity remains unquantified at the global level. A better understanding of the economic burden could help to inform resource prioritisation and motivate efforts to increase levels of physical activity worldwide.
Methods: Direct health-care costs, productivity losses, and disability-adjusted life-years (DALYs) attributable to physical inactivity were estimated with standardised methods and the best data available for 142 countries, representing 93·2% of the world’s population. Direct health-care costs and DALYs were estimated for coronary heart disease, stroke, type 2 diabetes, breast cancer, and colon cancer attributable to physical inactivity. Productivity losses were estimated with a friction cost approach for physical inactivity related mortality. Analyses were based on national physical inactivity prevalence from available countries, and adjusted population attributable fractions (PAFs) associated with physical inactivity for each disease outcome and all-cause mortality.
Findings: Conservatively estimated, physical inactivity cost health-care systems international $ (INT$) 53·8 billion worldwide in 2013, of which $31·2 billion was paid by the public sector, $12·9 billion by the private sector, and $9·7 billion by households. In addition, physical inactivity related deaths contribute to $13·7 billion in productivity losses, and physical inactivity was responsible for 13·4 million DALYs worldwide. High-income countries bear a larger proportion of economic burden (80·8% of health-care costs and 60·4% of indirect costs), whereas low-income and middle-income countries have a larger proportion of the disease burden (75·0% of DALYs). Sensitivity analyses based on less conservative assumptions led to much higher estimates.
Interpretation: In addition to morbidity and premature mortality, physical inactivity is responsible for a substantial economic burden. This paper provides further justification to prioritise promotion of regular physical activity worldwide as part of a comprehensive strategy to reduce non-communicable diseases.
A new “Cinema 3D” display lets audiences watch 3-D films in a movie theater without cumbersome glasses.
Developed by a team from MIT’s Computer Science and Artificial Intelligence Lab (CSAIL) and Weizmann Institute of Science, the prototype display uses a special array of lenses and mirrors to enable viewers to watch a 3-D movie from any seat in a theater.
Glasses-free 3-D already exists: Traditional methods for TV sets use a series of slits in front of the screen (a “parallax barrier”) that allows each eye to see a different set of pixels, creating a simulated sense of depth.
But because parallax barriers have to be at a consistent distance from the viewer, this approach isn’t practical for larger spaces like theaters, which have viewers at different angles and distances. Other methods, including one from the MIT Media Lab, involve developing completely new physical projectors that cover the entire angular range of the audience. However, this often comes at a cost of lower image-resolution.
The key insight with Cinema 3D is that people in movie theaters move their heads only over a very small range of angles, limited by the width of their seat. So it’s enough to display images to a narrow range of angles and replicate that to all seats in the theater, using a series of mirrors and lenses. (The team’s prototype requires 50 sets of mirrors and lenses, which is currently expensive and impractical, the researchers say.)
The team presented Cinema 3D in an open-access paper at last week’s SIGGRAPH computer-graphics conference in Anaheim, California. The work was funded by the Israel Science Foundation and the European Research Council.
MITCSAIL | Cinema 3D: A movie screen for glasses-free 3D
Abstract of Cinema 3D: large scale automultiscopic display
While 3D movies are gaining popularity, viewers in a 3D cinema still need to wear cumbersome glasses in order to enjoy them. Automultiscopic displays provide a better alternative to the display of 3D content, as they present multiple angular images of the same scene without the need for special eyewear. However, automultiscopic displays cannot be directly implemented in a wide cinema setting due to variants of two main problems: (i) The range of angles at which the screen is observed in a large cinema is usually very wide, and there is an unavoidable tradeoff between the range of angular images supported by the display and its spatial or angular resolutions. (ii) Parallax is usually observed only when a viewer is positioned at a limited range of distances from the screen. This work proposes a new display concept, which supports automultiscopic content in a wide cinema setting. It builds on the typical structure of cinemas, such as the fixed seat positions and the fact that different rows are located on a slope at different heights. Rather than attempting to display many angular images spanning the full range of viewing angles in a wide cinema, our design only displays the narrow angular range observed within the limited width of a single seat. The same narrow range content is then replicated to all rows and seats in the cinema. To achieve this, it uses an optical construction based on two sets of parallax barriers, or lenslets, placed in front of a standard screen. This paper derives the geometry of such a display, analyzes its limitations, and demonstrates a proof-of-concept prototype.
UNC Health Care | UNC Science Short: Sleep Spindles
University of North Carolina (UNC) School of Medicine scientists report using transcranial alternating current stimulation (tACS) to enhance memory during sleep, laying the groundwork for a new treatment paradigm for neurological and psychiatric disorders.
The findings, published in the journal Current Biology, offer a non-invasive method to potentially help millions of people with conditions such as autism, Alzheimer’s disease, schizophrenia, and major depressive disorder.
Do sleep spindles cause memory consolidation? The experiment.
For years, researchers have recorded electrical brain activity that oscillates or alternates during sleep on an electroencephalogram (EEG) as waves called sleep spindles. And scientists have suspected their involvement in cataloging and storing memories as we sleep.
“But we didn’t know if sleep spindles enable or even cause memories to be stored and consolidated,” said senior author UNC neuroscientist Flavio Frohlich, PhD, assistant professor of psychiatry and member of the UNC Neuroscience Center. “They could’ve been merely byproducts of other brain processes that enabled what we learn to be stored as a memory. But our study shows that, indeed, the spindles are crucial for the process of creating memories we need for everyday life. And we can target them to enhance memory.”
During Frohlich’s study, 16 male participants underwent a screening night of sleep before completing two nights of sleep for the study.
Before going to sleep each night, all participants performed two common memory exercises — associative word-pairing tests and motor sequence tapping tasks, which involved repeatedly finger-tapping a specific sequence. During both study nights, each participant had electrodes placed at specific spots on their scalps. During sleep one of the nights, each person received tACS — an alternating current of weak electricity synchronized with the brain’s natural sleep spindles. During sleep the other night, each person received sham stimulation as placebo.
Direct causal link
Each morning, researchers had participants perform the same standard memory tests. Frohlich’s team found no improvement in test scores for associative word-pairing but a significant improvement in the motor tasks when comparing the results between the stimulation and placebo night.
“This demonstrated a direct causal link between the electric activity pattern of sleep spindles and the process of motor memory consolidation.” Frohlich said.
This marks the first time a research group has reported selectively targeting sleep spindles without also increasing other natural electrical brain activity during sleep. This has never been accomplished with tDCS* (transcranial direct current stimulation), the much more popular cousin of tACS in which a constant stream of weak electrical current is applied to the scalp (see Neuroscience researchers caution public about hidden risks of self-administered brain stimulation*).
“We’re excited about this because we know sleep spindles, along with memory formation, are impaired in a number of disorders, such as schizophrenia and Alzheimer’s,” said Caroline Lustenberger, PhD, first author and postdoctoral fellow in the Frohlich lab. “We hope that targeting these sleep spindles could be a new type of treatment for memory impairment and cognitive deficits.”
The challenging research ahead
Frohlich said the next step is to try the same type of non-invasive brain stimulation in patients that have known deficits in these spindle activity patterns.
Based on the Current Biology paper, it’s clear the team is just getting started, with a lot of interesting possibilities to explore. For example, they note that “it is still unclear which specific cortical regions might be involved in sleep-dependent memory consolidation.”
It’s a sort of jungle in there, one with unknown species. The researchers say they may target posterior brain regions using faster frequencies (e.g., 15 Hz tACS) to optimally benefit motor memory consolidation, for example, and that maybe they should try synchronization of frontal oscillatory activity. And they want to find out if spindles synchronized across cortical regions are “essential for memory consolidation to occur” or are only spindles localized to brain regions necessary for performing the task?
Future studies will also be needed to investigate more complex ‘‘real-life’’ motor tasks that benefit from sleep and to relate those findings to sleep spindles, they add. “Future studies are also needed to further find optimized stimulation parameters by means of ideal stimulation location (centro-parietal instead of frontal) and (spindle) frequency applied.”
And when it comes to developing neuro-therapeutics, things will get even wilder. Will anomalous spindle patterns need to be reconstructed and reinforced, or will whole new customized patterns be needed? And if so, would this be some kind of reconstruction of a person’s memory (at least, their motor memory, for starters)? and what about dealing with circadian desynchronization and its possible disruptive effects on spindle patterns? And does it makes sense to look at phase patterns, in addition to frequency?
And perhaps most interesting to Kurzweilians, could the ability to improve spindle patterns, using machine learning, lead one day to cyborg minds and merged human-machine superintelligence?
KurzweilAI will be closely following this fascinating research.
The study was funded by the National Institutes of Health, UNC Department of Psychiatry, UNC School of Medicine, and Swiss National Science Foundation.
* We asked Frohlich to comment on possible risks similar to those reported with tDCS. “So far, tACS used in laboratory studies (i.e., in a well-controlled environment) has been very safe and we have never experienced serious side effects in any of our tACS studies,” he said. “However, unregulated DIY use of tACS could indeed theoretically carry risks, albeit we do not know at this point.”
Abstract of Feedback-Controlled Transcranial Alternating Current Stimulation Reveals a Functional Role of Sleep Spindles in Motor Memory Consolidation
Transient episodes of brain oscillations are a common feature of both the waking and the sleeping brain. Sleep spindles represent a prominent example of a poorly understood transient brain oscillation that is impaired in disorders such as Alzheimer’s disease and schizophrenia. However, the causal role of these bouts of thalamo-cortical oscillations remains unknown. Demonstrating a functional role of sleep spindles in cognitive processes has, so far, been hindered by the lack of a tool to target transient brain oscillations in real time. Here, we show, for the first time, selective enhancement of sleep spindles with non-invasive brain stimulation in humans. We developed a system that detects sleep spindles in real time and applies oscillatory stimulation. Our stimulation selectively enhanced spindle activity as determined by increased sigma activity after transcranial alternating current stimulation (tACS) application. This targeted modulation caused significant enhancement of motor memory consolidation that correlated with the stimulation-induced change in fast spindle activity. Strikingly, we found a similar correlation between motor memory and spindle characteristics during the sham night for the same spindle frequencies and electrode locations. Therefore, our results directly demonstrate a functional relationship between oscillatory spindle activity and cognition.
MIT researchers have developed a new technique for imaging brain tissue at multiple scales, allowing them to peer at molecules within cells or take a wider view of the long-range connections between neurons.
This technique, known as “magnified analysis of proteome” (MAP), should help scientists in their ongoing efforts to chart the connectivity and functions of neurons in the human brain, says Kwanghun Chung, the Samuel A. Goldblith Assistant Professor in the Department of Chemical Engineering, extending the work of Sebastian Seung and colleagues on the Human Connectome Project.
“We use a chemical process to make the whole brain size-adjustable, while preserving pretty much everything. We preserve the proteome (the collection of proteins found in a biological sample), we preserve nanoscopic details, and we also preserve brain-wide connectivity,” says Chung, the senior author of a paper describing the method in the July 25 issue of Nature Biotechnology.
The researchers also showed that the technique is applicable to other organs such as the heart, lungs, liver, and kidneys.
The new MAP technique builds on a tissue transformation method known as CLARITY, which Chung developed as a postdoc at Stanford University. CLARITY preserves cells and molecules in brain tissue and makes them transparent so the molecules inside the cell can be imaged in 3-D. In the new study, Chung sought a way to image the brain at multiple scales, within the same tissue sample.*
There are hundreds of thousands of commercially available antibodies that can be used to fluorescently tag specific proteins. In this study, the researchers imaged neuronal structures such as axons and synapses by labeling proteins found in those structures, and they also labeled proteins that allow them to distinguish neurons from glial cells.
“We can use these antibodies to visualize any target structures or molecules,” Chung says. “We can visualize different neuron types and their projections to see their connectivity. We can also visualize signaling molecules or functionally important proteins.”High resolution
Once the tissue is expanded, the researchers can use any of several common microscopes to obtain images with a resolution as high as 60 nanometers — much better than the usual 200 to 250-nanometer limit of light microscopes, which are constrained by the wavelength of visible light. The researchers also demonstrated that this approach works with relatively large tissue samples, up to 2 millimeters thick.
“This is, as far as I know, the first demonstration of super-resolution proteomic imaging of millimeter-scale samples,” Chung says.
“This is an exciting advance for brain mapping, a technique that reveals the molecular and connectional architecture of the brain with unprecedented detail,” says Seung, a professor of computer science at the Princeton Neuroscience Institute, who was not involved in the research.
Currently, efforts to map the connections of the human brain rely on electron microscopy, but Chung and colleagues demonstrated that the higher-resolution MAP imaging technique can trace those connections more accurately.
Chung’s lab is now working on speeding up the imaging and the image processing, which is challenging because there is so much data generated from imaging the expanded tissue samples. “It’s already easier than other techniques because the process is really simple and you can use off-the-shelf molecular markers, but we are trying to make it even simpler,” Chung says.
* To achieve that, the researchers developed a method to reversibly expand tissue samples in a way that preserves nearly all of the proteins within the cells. Those proteins can then be labeled with fluorescent molecules and imaged.
The technique relies on flooding the brain tissue with acrylamide polymers, which can form a dense gel. In this case, the gel is 10 times denser than the one used for the CLARITY technique, which gives the sample much more stability. This stability allows the researchers to denature and dissociate the proteins inside the cells without destroying the structural integrity of the tissue sample.
Before denaturing the proteins, the researchers attach them to the gel using formaldehyde, as Chung did in the CLARITY method. Once the proteins are attached and denatured, the gel expands the tissue sample to four or five times its original size.
“It is reversible and you can do it many times,” Chung says. “You can then use off-the-shelf molecular markers like antibodies to label and visualize the distribution of all these preserved biomolecules.”
More on this News Release
Imaging the brain at multiple size scales
Melanie Gonick/MIT | MIT researchers have developed a new technique for imaging brain tissue at multiple scales, allowing them to peer at molecules within cells or take a wider view of the long-range connections between neurons.
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- Nature Biotechnology
Abstract of Multiplexed and scalable super-resolution imaging of three-dimensional protein localization in size-adjustable tissues
The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnified analysis of the proteome (MAP), linearly expands entire organs fourfold while preserving their overall architecture and three-dimensional proteome organization. MAP is based on the observation that preventing crosslinking within and between endogenous proteins during hydrogel-tissue hybridization allows for natural expansion upon protein denaturation and dissociation. The expanded tissue preserves its protein content, its fine subcellular details, and its organ-scale intercellular connectivity. We use off-the-shelf antibodies for multiple rounds of immunolabeling and imaging of a tissue’s magnified proteome, and our experiments demonstrate a success rate of 82% (100/122 antibodies tested). We show that specimen size can be reversibly modulated to image both inter-regional connections and fine synaptic architectures in the mouse brain.