Tag Archives: University of California at Irvine

Revival of dead pig brains raises moral questions about life and death

The line between life and death may not be what we thought it was according to some research that was reported in April 2019. Ed Wong’s April 17, 2019 article (behind a paywall) for The Atlantic was my first inkling about the life-death questions raised by some research performed at Yale University, (Note: Links have been removed)

The brain, supposedly, cannot long survive without blood. Within seconds, oxygen supplies deplete, electrical activity fades, and unconsciousness sets in. If blood flow is not restored, within minutes, neurons start to die in a rapid, irreversible, and ultimately fatal wave.

But maybe not? According to a team of scientists led by Nenad Sestan at Yale School of Medicine, this process might play out over a much longer time frame, and perhaps isn’t as inevitable or irreparable as commonly believed. Sestan and his colleagues showed this in dramatic fashion—by preserving and restoring signs of activity in the isolated brains of pigs that had been decapitated four hours earlier.

The team sourced 32 pig brains from a slaughterhouse, placed them in spherical chambers, and infused them with nutrients and protective chemicals, using pumps that mimicked the beats of a heart. This system, dubbed BrainEx, preserved the overall architecture of the brains, preventing them from degrading. It restored flow in their blood vessels, which once again became sensitive to dilating drugs. It stopped many neurons and other cells from dying, and reinstated their ability to consume sugar and oxygen. Some of these rescued neurons even started to fire. “Everything was surprising,” says Zvonimir Vrselja, who performed most of the experiments along with Stefano Daniele.

… “I don’t see anything in this report that should undermine confidence in brain death as a criterion of death,” says Winston Chiong, a neurologist at the University of California at San Francisco. The matter of when to declare someone dead has become more controversial since doctors began relying more heavily on neurological signs, starting around 1968, when the criteria for “brain death” were defined. But that diagnosis typically hinges on the loss of brainwide activity—a line that, at least for now, is still final and irreversible. After MIT Technology Review broke the news of Sestan’s work a year ago, he started receiving emails from people asking whether he could restore brain function to their loved ones. He very much cannot. BrainEx isn’t a resurrection chamber.

“It’s not going to result in human brain transplants,” adds Karen Rommelfanger, who directs Emory University’s neuroethics program. “And I don’t think this means that the singularity is coming, or that radical life extension is more possible than before.”

So why do the study? “There’s potential for using this method to develop innovative treatments for patients with strokes or other types of brain injuries, and there’s a real need for those kinds of treatments,” says L. Syd M Johnson, a neuroethicist at Michigan Technological University. The BrainEx method might not be able to fully revive hours-dead brains, but Yama Akbari, a critical-care neurologist at the University of California at Irvine, wonders whether it would be more successful if applied minutes after death. Alternatively, it could help to keep oxygen-starved brains alive and intact while patients wait to be treated. “It’s an important landmark study,” Akbari says.

Yong notes that the study still needs to be replicated in his article which also probes some of the ethical issues associated with the latest neuroscience research.

Nature published the Yale study,

Restoration of brain circulation and cellular functions hours post-mortem by Zvonimir Vrselja, Stefano G. Daniele, John Silbereis, Francesca Talpo, Yury M. Morozov, André M. M. Sousa, Brian S. Tanaka, Mario Skarica, Mihovil Pletikos, Navjot Kaur, Zhen W. Zhuang, Zhao Liu, Rafeed Alkawadri, Albert J. Sinusas, Stephen R. Latham, Stephen G. Waxman & Nenad Sestan. Nature 568, 336–343 (2019) DOI: https://doi.org/10.1038/s41586-019-1099-1 Published 17 April 2019 Issue Date 18 April 2019

This paper is behind a paywall.

Two neuroethicists had this to say (link to their commentary in Nature follows) as per an April 71, 2019 news release from Case Western Reserve University (also on EurekAlert), Note: Links have been removed,

The brain is more resilient than previously thought. In a groundbreaking experiment published in this week’s issue of Nature, neuroscientists created an artificial circulation system that successfully restored some functions and structures in donated pig brains–up to four hours after the pigs were butchered at a USDA food processing facility. Though there was no evidence of restored consciousness, brains from the pigs were without oxygen for hours, yet could still support key functions provided by the artificial system. The result challenges the notion that mammalian brains are fully and irreversibly damaged by a lack of oxygen.

“The assumptions have always been that after a couple minutes of anoxia, or no oxygen, the brain is ‘dead,'” says Stuart Youngner, MD, who co-authored a commentary accompanying the study with Insoo Hyun, PhD, both professors in the Department of Bioethics at Case Western Reserve University School of Medicine. “The system used by the researchers begs the question: How long should we try to save people?”

In the pig experiment, researchers used an artificial perfusate (a type of cell-free “artificial blood”), which helped brain cells maintain their structure and some functions. Resuscitative efforts in humans, like CPR, are also designed to get oxygen to the brain and stave off brain damage. After a period of time, if a person doesn’t respond to resuscitative efforts, emergency medical teams declare them dead.

The acceptable duration of resuscitative efforts is somewhat uncertain. “It varies by country, emergency medical team, and hospital,” Youngner said. Promising results from the pig experiment further muddy the waters about the when to stop life-saving efforts.

At some point, emergency teams must make a critical switch from trying to save a patient, to trying to save organs, said Youngner. “In Europe, when emergency teams stop resuscitation efforts, they declare a patient dead, and then restart the resuscitation effort to circulate blood to the organs so they can preserve them for transplantation.”

The switch can involve extreme means. In the commentary, Youngner and Hyun describe how some organ recovery teams use a balloon to physically cut off blood circulation to the brain after declaring a person dead, to prepare the organs for transplantation.

The pig experiment implies that sophisticated efforts to perfuse the brain might maintain brain cells. If technologies like those used in the pig experiment could be adapted for humans (a long way off, caution Youngner and Hyun), some people who, today, are typically declared legally dead after a catastrophic loss of oxygen could, tomorrow, become candidates for brain resuscitation, instead of organ donation.

Said Youngner, “As we get better at resuscitating the brain, we need to decide when are we going to save a patient, and when are we going to declare them dead–and save five or more who might benefit from an organ.”

Because brain resuscitation strategies are in their infancy and will surely trigger additional efforts, the scientific and ethics community needs to begin discussions now, says Hyun. “This study is likely to raise a lot of public concerns. We hoped to get ahead of the hype and offer an early, reasoned response to this scientific advance.”

Both Youngner and Hyun praise the experiment as a “major scientific advancement” that is overwhelmingly positive. It raises the tantalizing possibility that the grave risks of brain damage caused by a lack of oxygen could, in some cases, be reversible.
“Pig brains are similar in many ways to human brains, which makes this study so compelling,” Hyun said. “We urge policymakers to think proactively about what this line of research might mean for ongoing debates around organ donation and end of life care.”

Here’s a link to and a citation to the Nature commentary,

Pig experiment challenges assumptions around brain damage in people by Stuart Youngner and Insoo Hyun. Nature 568, 302-304 (2019) DOI: 10.1038/d41586-019-01169-8 April 17, 2019

This paper is open access.

I was hoping to find out more about BrainEx, but this April 17, 2019 US National Institute of Mental Health news release is all I’ve been able to find in my admittedly brief online search. The news release offers more celebration than technical detail.

Quick comment

Interestingly, there hasn’t been much of a furor over this work. Not yet.

Snakebite? Roll out the nanoparticles

An October 4, 2018 news item on Nanowerk highlights some recent research into treating snakebites (Note: A link has been removed),

Venomous snakebites affect 2.5 million people, and annually cause more than 100,000 deaths and leave 400,000 individuals with permanent physical and psychological trauma each year.

Researchers reporting in PLOS Neglected Tropical Diseases (“Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis”) have now described a new approach to treating snake bites [sic], using nanoparticles to bind to venom toxins and prevent the spread of venom through the body.

Caption: “Synthetic polymer nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis.” Credit: Shea, et al. CC BY 4.0: Redistribution allowed with credit

An October 4, 2018 PLOS news release on EurekAlert, which originated the news item, expands on the theme,

The standard treatment for snakebites is the intravenous administration of IgG immune molecules that recognize venoms. However, such antivenom therapies must be administered quickly–and by trained healthcare workers– to be effective and are highly specific to particular venoms. There is an ongoing need for a snakebite treatment which can be used in a rural setting and works against the bites of diverse venomous snakes.

In the new work, Kenneth Shea, of the University of California, Irvine, and colleagues engineered nanoparticles that bind to and sequester an array of phospholipases A2 (PLA2) and three-finger toxin (3FTX) molecules found in Elapidae snake venoms. The Elapidae family is a large family of venomous snakes that includes cobras, kraits, tiger snakes, sea snakes, coral snakes and mambas, among other species. The researchers tested the ability of the nanoparticles to block Naja nigricollis (black-necked spitting cobra) venom in mice that received varying doses of the nanoparticles, injected into the skin. Envenomings by this snake in sub-Saharan Africa inflict serious cutaneous necrosis that may leave permanent tissue damage in the victims.

In experiments on isolated cells, the nanoparticles were found to sequester a wide range of Elapidae PLA and 3FTX venoms. Moreover, with collaborator José María Gutiérrez from the Instituto Clodomiro Picado (Universidad de Costa Rica), experiments with mice demonstrated that injections of the nanoparticles at the site of venom injection significantly mitigated the typical necrotic effects–including blistering and ulcers– of the spitting cobra venom. The nanoparticles administered to mice that had not received venom did not have an effect on skin and did not induce systemic toxicity.

“The stable, low-cost nanoparticles have the potential to be administered subcutaneously immediately after the bite at the site of envenoming by this spitting cobra to halt or reduce the extent of local damage and mitigate the systemic distribution of toxins post-envenoming,” the researchers say.

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

Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis by Jeffrey O’Brien, Shih-Hui Lee, José María Gutiérrez, Kenneth J. Shea. PLOS Neglected Tropical Diseases 12(10): e0006736 DOI: https://doi.org/10.1371/journal.pntd.0006736 Published: October 4, 2018

This paper is open access. By the way, PLOS stands for Public Library of Science.

Making lead look like gold (so to speak)

Apparently you can make lead ‘look’ like gold if you can get it to reflect light in the same way. From a Feb. 28, 2017 news item on Nanowerk (Note: A link has been removed),

Since the Middle Ages, alchemists have sought to transmute elements, the most famous example being the long quest to turn lead into gold. Transmutation has been realized in modern times, but on a minute scale using a massive particle accelerator.

Now, theorists at Princeton University have proposed a different approach to this ancient ambition — just make one material behave like another. A computational theory published Feb. 24 [2017] in the journal Physical Review Letters (“How to Make Distinct Dynamical Systems Appear Spectrally Identical”) demonstrates that any two systems can be made to look alike, even if just for the smallest fraction of a second.

In this context, for two objects to “look” like each other, they need to reflect light in the same way. The Princeton researchers’ method involves using light to make non-permanent changes to a substance’s molecules so that they mimic the reflective properties of another substance’s molecules. This ability could have implications for optical computing, a type of computing in which electrons are replaced by photons that could greatly enhance processing power but has proven extremely difficult to engineer. It also could be applied to molecular detection and experiments in which expensive samples could be replaced by cheaper alternatives.

A Feb. 28, 2017 Princeton University news release (also on EurekAlert) by Tien Nguyen, which originated the news item, expands on the theme (Note: Links have been removed),

“It was a big shock for us that such a general statement as ‘any two objects can be made to look alike’ could be made,” said co-author Denys Bondar, an associate research scholar in the laboratory of co-author Herschel Rabitz, Princeton’s Charles Phelps Smyth ’16 *17 Professor of Chemistry.

The Princeton researchers posited that they could control the light that bounces off a molecule or any substance by controlling the light shone on it, which would allow them to alter how it looks. This type of manipulation requires a powerful light source such as an ultrafast laser and would last for only a femtosecond, or one quadrillionth of a second. Unlike normal light sources, this ultrafast laser pulse is strong enough to interact with molecules and distort their electron cloud while not actually changing their identity.

“The light emitted by a molecule depends on the shape of its electron cloud, which can be sculptured by modern lasers,” Bondar said. Using advanced computational theory, the research team developed a method called “spectral dynamic mimicry” that allowed them to calculate the laser pulse shape, which includes timing and wavelength, to produce any desired spectral output. In other words, making any two systems look alike.

Conversely, this spectral control could also be used to make two systems look as different from one another as possible. This differentiation, the researchers suggested, could prove valuable for applications of molecular detections such as identifying toxic versus safe chemicals.

Shaul Mukamel, a chemistry professor at the University of California-Irvine, said that the Princeton research is a step forward in an important and active research field called coherent control, in which light can be manipulated to control behavior at the molecular level. Mukamel, who has collaborated with the Rabitz lab but was not involved in the current work, said that the Rabitz group has had a prominent role in this field for decades, advancing technology such as quantum computing and using light to drive artificial chemical reactivity.

“It’s a very general and nice application of coherent control,” Mukamel said. “It demonstrates that you can, by shaping the optical paths, bring the molecules to do things that you want beforehand — it could potentially be very significant.”

Since the Middle Ages, alchemists have sought to transmute elements, the most famous example being the long quest to turn lead into gold. Now, theorists at Princeton University have proposed a different approach to this ancient ambition — just make one material behave like another, even if just for the smallest fraction of a second. The researchers are, left to right, Renan Cabrera, an associate research scholar in chemistry; Herschel Rabitz, Princeton’s Charles Phelps Smyth ’16 *17 Professor of Chemistry; associate research scholar in chemistry Denys Bondar; and graduate student Andre Campos. (Photo by C. Todd Reichart, Department of Chemistry)

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

How to Make Distinct Dynamical Systems Appear Spectrally Identical by
Andre G. Campos, Denys I. Bondar, Renan Cabrera, and Herschel A. Rabitz.
Phys. Rev. Lett. 118, 083201 (Vol. 118, Iss. 8) DOI:https://doi.org/10.1103/PhysRevLett.118.083201 Published 24 February 2017

© 2017 American Physical Society

This paper is behind a paywall.

Bedbugs: a bean-based solution from the Balkans or an artificial spider web solution from Fibertrap

Today (Apr. 10, 2013), I came across two news items about ridding oneself of bedbugs. Given the amount of coverage the pests and their growing ubiquity have been receiving the last few years, it seems that at some point everyone will experience an infestation. So, it’s good to see that scientists and entrepreneurs are working on solutions.

First up, there’s a team of scientists who are studying how people in the Balkans rid themselves of bedbugs, from the Apr. 9, 2013 news item on ScienceDaily,

Inspired by a traditional Balkan bedbug remedy, researchers have documented how microscopic hairs on kidney bean leaves effectively stab and trap the biting insects, according to findings published online today [Apr. 9, 2013] in the Journal of the Royal Society Interface. Scientists at UC [University of California] Irvine and the University of Kentucky are now developing materials that mimic the geometry of the leaves.

I knew they were a problem but I hadn’t realized how very hardy the bugs are, from the news item,

Bedbugs have made a dramatic comeback in the U.S. in recent years, infesting everything from homes and hotels to schools, movie theaters and hospitals. Although not known to transmit disease, their bites can cause burning, itching, swelling and psychological distress. It helps to catch infestations early, but the nocturnal parasites’ ability to hide almost anywhere, breed rapidly and “hitchhike” from place to place makes detection difficult. They can survive as long as a year without a blood meal.

Current commercial prevention methods, including freezing, extreme heating, vacuuming and pesticides, can be costly and unreliable. Many sufferers resort to ineffective, potentially dangerous measures, such as spraying nonapproved insecticides themselves rather than hiring a professional.

The University of California Irvine Apr. 9, 2013 news release, which originated the news item, describes the researchers’ [Doctoral student Megan Szyndler, entomologist Catherine Loudon and chemist Robert Corn of UC Irvine and entomologists Kenneth Haynes and Michael Potter of the University of Kentucky] inspiration, the bean leaves, at more length and the proposed bedbug solution,

Their work was motivated by a centuries-old remedy for bedbugs used in Bulgaria, Serbia and other southeast European countries. Kidney bean leaves were strewn on the floor next to beds and seemed to ensnare the blood-seeking parasites on their nightly forays. The bug-encrusted greenery was burned the next morning to exterminate the insects.

Through painstaking detective work, the scientists discovered that the creatures are trapped within seconds of stepping on a leaf, their legs impaled by microscopic hooked hairs known botanically as trichomes.

Using the bean leaves as templates, the researchers have microfabricated materials that closely resemble them geometrically. The synthetic surfaces snag the bedbugs temporarily but do not yet stop them as effectively as real leaves, Loudon said, suggesting that crucial mechanics of the trichomes still need to be determined.

Theoretically, bean leaves could be used for pest control, but they dry out and don’t last very long. They also can’t easily be applied to locations other than a floor. Synthetic materials could provide a nontoxic alternative.

“Plants exhibit extraordinary abilities to entrap insects,” said Loudon, lead author of the paper. “Modern scientific techniques let us fabricate materials at a microscopic level, with the potential to ‘not let the bedbugs bite’ without pesticides.”

“Nature is a hard act to follow, but the benefits could be enormous,” Potter said. “Imagine if every bedbug inadvertently brought into a dwelling was captured before it had a chance to bite and multiply.”

Here’s a citation and link to the article,

Entrapment of bed bugs by leaf trichomes inspires microfabrication of biomimetic surfaces by Megan W. Szyndler,  Kenneth F. Haynes, Michael F. Potter, Robert M. Corn,
and Catherine Loudon. J. R. Soc. Interface. 2013 10 83 20130174; doi:10.1098/rsif.2013.0174 (published 10 April 2013) 1742-5662

This article is open access.

Moving onto the second bedbug item, Azonano features an Apr. 10, 2013 news item about Fibertrap and its artificial spider web trap for bedbugs,

A breakthrough and innovative solution to the growing plague of bedbugs is about to impact the lives of people suffering from one of the world’s most tenacious pests. Fibertrap is a New York based firm that has developed a revolutionary new way to stop bedbugs, termites and other pests without the use of harmful and toxic chemicals and instead by using an artificial, micro-fiber spider web.

Here’s more about how this solution works,

As the war against bedbugs rages on these nasty insects have become increasingly resistant to pesticides and other common methods of pest control. Fibertrap’s ground-breaking new method addresses the fundamental weakness in all bedbugs and pests: mobility. Utilizing micro-fibers 50 times thinner than human hair, Fibertrap entangles the bugs as they crawl trapping them in the man-made web. Without the ability to move and seek food the creatures will die, ceasing re-production and preventing the establishment of infestation.

Most often, bedbugs move between walls via electrical outlets to unsuspecting home and business owners. To help prevent bedbug migration, Fibertrap intends to produce easy to use traps and insulation products using this innovative new web-like material that will allow the consumer to protect their homes, apartments, offices and dorm rooms with ease and peace of mind.

You can read more about it at Azonano or you can try the Fibertrap website. I cannot find any information about purchasing a Fibertrap product. I think this is publicity designed to excite interest and further investment so these materials ,which are currently at a prototype stage, can be brought to market.

I hope someone is able to get a pest control product for bedbugs to us soon.

MORPHONANO, an art/sci exhibit in California

This description of the event (MORPHONANO) which is being held at the Beall Center at the University of California (Irvine) comes from the Beall Center’s home page,

MORPHONANO explores a number of art works created by media artist Victoria Vesna and nanoscientist James Gimzewski. Their collaborative works create an intersection of space, time and embodiment by employing a very subtle and responsive energetic exchange. Participants interact with the works in mindful ways resulting in rich visual and sonic experiences within a meditative space. By reversing the scale of nanotechnology to the realm of human experience, the artist and scientist create a sublime reversal of space-time.

Here’s an image depicting one of the exhibits in the show,

ZERO@WAVEFUNCTION plays with the idea of scale and molecular manipulation from a distance with the participant changing the structures of the buckyballs with their shadows, a real time interactive metaphor of the scanning tunneling microscope (STM).

It looks to me that the idea is to ’embody’ the nanoscale as per the caption “the participants changing the structures of the buckyballs with their shadows, a real time interactive metaphor of the scanning tunneling microscope.” There’s a larger version of the image and information about this exhibit in the Feb. 14, 2012 news item on Nanowerk,

BLUE MORPH is an interactive installation that uses nanoscale images combined with sounds derived from the microscopic undulations of a chrysalis during the period of its metamorphosis into a butterfly recorded using nanotechnology. The work is designed to be responsive to minute, subtle, mindful movements of the participant creating a rich visual and sonic experience of morphing. Most is revealed in complete stillness.

NANOMANDALA is a video projected onto a disk of sand, 8 feet in diameter. Visitors can touch the sand as images are projected in evolving scale from the molecular structure of a single grain of sand – achieved my means of photography, optical and scanning electron microscopy (SEM) – to the recognizable image of the complete mandala, and then back again. The original Chakrasamvara mandala was created by monks of the Ghaden Lhopa Khangsten monastery. Patience will allow experiencing the whole.

ZERO@WAVEFUNCTION plays with the idea of scale and molecular manipulation from a distance with the participant changing the structures of the buckyballs with their shadows, a real time interactive metaphor of the scanning tunneling microscope (STM). Slow motion makes change happen.

BRAIN STORMING: SOUNDS OF THINKING a premier of a work of self organization in progress focusing on scale invariant and the brain using biometric data. A number of brain storming sessions with cutting neuroscientists, nanotechnologists, philosophers and monks will take place throughout the exhibition. In many ways the works in this exhibition reverse the scale of nanotechnology to a visible realm and time in nano scale creating a sublime reversal of space-time.

The show opened Feb. 2 and closes May 6, 2012. The address is

Beall Center for Art + Technology
University of California, Irvine
Claire Trevor School of the Arts
712 Arts Plaza
Irvine, CA 92697-2775
www.beallcenter.uci.edu

Here are some details about the art/sci collaborators, Victoria Vesna and James Gimzewski, from the undated Beall Center news release,

Victoria Vesna is a media artist and Professor at the Department of Design | Media Arts at the UCLA School of the Arts and director of the UCLA Art|Sci center. Currently she is Visiting Professor at Art, Media + Technology, Parsons the New School for Design in New York and a senior researcher at IMéRA – Institut Méditerranéen de Recherches Avancées in Marseille, France. Her work can be defined as experimental creative research that resides between disciplines and technologies. She explores how communication technologies affect collective behavior and how perceptions of identity shift in relation to scientific innovation. Her most recent experiential installations — Blue Morph, Water Bowls, Hox Zodiac, all aim to raise consciousness around environmental issues natural and human-animal relations. …

James Gimzewski FRS is a distinguished Professor in the Dept. of Chemistry and Biochemistry at UCLA. He is director of Pico and Nano core laboratory at the California NanoSynstems Institute (CNSI). He is also scientific director of the Art | Sci center and a senior fellow of IMéRA. He is a satellite co-director and PI of materials nanoarchitectonics at the National Institute of Material Science in Tsukuba, Japan. Until February 2001, he was a group leader at the IBM Zurich Labs, where he was involved in Nanoscale science since 1983. He pioneered research on electrical contact with single atoms and molecules, light emission and molecular imaging using STM. His accomplishments include the first STM-manipulation of molecules at room temperature, the realization of molecular abacus using buckyballs, the discovery of single molecule rotors and the development of nanomechanical sensors based on nanotechnology, which explore the ultimate limits of sensitivity and measurement. …

I have mentioned Gimzewski previously in a post (Oct. 17, 2011) about a three-part nanotechnology series on Canadian television.