Tag Archives: Johanna Wilde

Reducing toxicity of Alzheimer’s proteins with graphene oxide

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Nobody really knows what causes Alzheimer’s disease (a form of dementia) so researchers continue to investigates the cause(s) and, also, possible remedies. An October 4, 2023 news item on ScienceDaily announces some of the latest research,

A probable early driver of Alzheimer’s disease is the accumulation of molecules called amyloid peptides. These cause cell death, and are commonly found in the brains of Alzheimer’s patients. Researchers at Chalmers University of Technology, Sweden, have now shown that yeast cells that accumulate these misfolded amyloid peptides can recover after being treated with graphene oxide nanoflakes.

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An October 4, 2023 Chalmers University of Technology press release (also received via email and on EurekAlert) by Susanne Nilsson Lindh & Johanna Wilde, which originated the news item, delves into the topic,

Alzheimer’s disease is an incurable brain disease, leading to dementia and death, that causes suffering for both the patients and their families. It is estimated that over 40 million people worldwide are living with the disease or a related form of dementia. According to Alzheimer’s News Today, the estimated global cost of these diseases is one percent of the global gross domestic product.

Misfolded amyloid-beta peptides, Aβ peptides, that accumulate and aggregate in the brain, are believed to be the underlying cause of Alzheimer’s disease. They trigger a series of harmful processes in the neurons (brain cells) – causing the loss of many vital cell functions or cell death, and thus a loss of brain function in the affected area. To date, there are no effective strategies to treat amyloid accumulation in the brain.

Researchers at Chalmers University of Technology have now shown that treatment with graphene oxide leads to reduced levels of aggregated amyloid peptides in a yeast cell model.

“This effect of graphene oxide has recently also been shown by other researchers, but not in yeast cells”, says Xin Chen, Researcher in Systems Biology at Chalmers and first author of the study. “Our study also explains the mechanism behind the effect. Graphene oxide affects the metabolism of the cells, in a way that increases their resistance to misfolded proteins and oxidative stress. This has not been previously reported.”

Investigating the mechanisms using baker’s yeast affected by Alzheimer’s disease
In Alzheimer’s disease, the amyloid aggregates exert their neurotoxic effects by causing various cellular metabolic disorders, such as stress in the endoplasmic reticulum – a major part of the cell, in which many of its proteins are produced. This can reduce cells’ ability to handle misfolded proteins, and consequently increase the accumulation of these proteins.

The aggregates also affect the function of the mitochondria, the cells’ powerhouses. Therefore, the neurons are exposed to increased oxidative stress (reactive molecules called oxygen radicals, which damage other molecules); something to which brain cells are particularly sensitive.

The Chalmers researchers have conducted the study by a combination of protein analysis (proteomics) and follow-up experiments. They have used baker’s yeast, Saccharomyces cerevisiae, as an in vivo model for human cells. Both cell types have very similar systems for controlling protein quality. This yeast cell model was previously established by the research group to mimic human neurons affected by Alzheimer’s disease.

“The yeast cells in our model resemble neurons affected by the accumulation of amyloid-beta42, which is the form of amyloid peptide most prone to aggregate formation”, says Xin Chen. “These cells age faster than normal, show endoplasmic reticulum stress and mitochondrial dysfunction, and have elevated production of harmful reactive oxygen radicals.”

High hopes for graphene oxide nanoflakes
Graphene oxide nanoflakes are two-dimensional carbon nanomaterials with unique properties, including outstanding conductivity and high biocompatibility. They are used extensively in various research projects, including the development of cancer treatments, drug delivery systems and biosensors.

The nanoflakes are hydrophilic (water soluble) and interact well with biomolecules such as proteins. When graphene oxide enters living cells, it is able to interfere with the self-assembly processes of proteins.

“As a result, it can hinder the formation of protein aggregates and promote the disintegration of existing aggregates”, says Santosh Pandit, Researcher in Systems Biology at Chalmers and co-author of the study. “We believe that the nanoflakes act via two independent pathways to mitigate the toxic effects of amyloid-beta42 in the yeast cells.”

In one pathway, graphene oxide acts directly to prevent amyloid-beta42 accumulation. In the other, graphene oxide acts indirectly by a (currently unknown) mechanism, in which specific genes for stress response are activated. This increases the cell’s ability to handle misfolded proteins and oxidative stress.

How to treat Alzheimer’s patients is still a question for the future. However, according to the research group at Chalmers, graphene oxide holds great potential for future research in the field of neurodegenerative diseases. The research group has already been able to show that treatment with graphene oxide also reduces the toxic effects of protein aggregates specific to Huntington’s disease in a yeast model.

“The next step is to investigate whether it is possible to develop a drug delivery system based on graphene oxide for Alzheimer’s disease.” says Xin Chen. “We also want to test whether graphene oxide has beneficial effects in additional models of neurodegenerative diseases, such as Parkinson’s disease.”

More about: proteins and peptides
Proteins and peptides are fundamentally the same type of molecule and are made up of amino acids. Peptide molecules are smaller – typically containing less than 50 amino acids – and have a less complicated structure. Proteins and peptides can both become deformed if they fold in the wrong way during formation in the cell. When many amyloid-beta peptides accumulate in the brain, the aggregates are classified as proteins.

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

Graphene Oxide Attenuates Toxicity of Amyloid-β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response by Xin Chen, Santosh Pandit, Lei Shi, Vaishnavi Ravikumar, Julie Bonne Køhler, Ema Svetlicic, Zhejian Cao, Abhroop Garg, Dina Petranovic, Ivan Mijakovic. Advanced Functional Materials Volume 33, Issue 45 November 2, 2023 2304053 DOI: https://doi.org/10.1002/adfm.202304053 First published online: 07 July 2023

This paper is open access.

Living with a mind-controlled prosthetic

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This could be described as the second half of an October 10, 2014 post (Mind-controlled prostheses ready for real world activities). Five and a half years later, Sweden’s Chalmers University of Technology has announced mind-controlled prosthetics in daily use that feature the sense of touch. From an April 30, 2020 Chalmers University of Technology press release (also on EurekAlert but published April 29, 2020) by Johanna Wilde,

For the first time, people with arm amputations can experience sensations of touch in a mind-controlled arm prosthesis that they use in everyday life. A study in the New England Journal of Medicine reports on three Swedish patients who have lived, for several years, with this new technology – one of the world’s most integrated interfaces between human and machine.

See the film: “The most natural robotic prosthesis in the world” [Should you not have Swedish language skills, you can click on the subtitle option in the video’s settings field]

The advance is unique: the patients have used a mind-controlled prosthesis in their everyday life for up to seven years. For the last few years, they have also lived with a new function – sensations of touch in the prosthetic hand. This is a new concept for artificial limbs, which are called neuromusculoskeletal prostheses – as they are connected to the user’s nerves, muscles, and skeleton.

The research was led by Max Ortiz Catalan, Associate Professor at Chalmers University of Technology, in collaboration with Sahlgrenska University Hospital, University of Gothenburg, and Integrum AB, all in Gothenburg, Sweden. Researchers at Medical University of Vienna in Austria and the Massachusetts Institute of Technology in the USA were also involved.

“Our study shows that a prosthetic hand, attached to the bone and controlled by electrodes implanted in nerves and muscles, can operate much more precisely than conventional prosthetic hands. We further improved the use of the prosthesis by integrating tactile sensory feedback that the patients use to mediate how hard to grab or squeeze an object. Over time, the ability of the patients to discern smaller changes in the intensity of sensations has improved,” says Max Ortiz Catalan.

“The most important contribution of this study was to demonstrate that this new type of prosthesis is a clinically viable replacement for a lost arm. No matter how sophisticated a neural interface becomes, it can only deliver real benefit to patients if the connection between the patient and the prosthesis is safe and reliable in the long term. Our results are the product of many years of work, and now we can finally present the first bionic arm prosthesis that can be reliably controlled using implanted electrodes, while also conveying sensations to the user in everyday life”, continues Max Ortiz Catalan.

Since receiving their prostheses, the patients have used them daily in all their professional and personal activities.

The new concept of a neuromusculoskeletal prosthesis is unique in that it delivers several different features which have not been presented together in any other prosthetic technology in the world:

[1] It has a direct connection to a person’s nerves, muscles, and skeleton.

[2] It is mind-controlled and delivers sensations that are perceived by the user as arising from the missing hand.

[3] It is self-contained; all electronics needed are contained within the prosthesis, so patients do not need to carry additional equipment or batteries.

[4] It is safe and stable in the long term; the technology has been used without interruption by patients during their everyday activities, without supervision from the researchers, and it is not restricted to confined or controlled environments.

The newest part of the technology, the sensation of touch, is possible through stimulation of the nerves that used to be connected to the biological hand before the amputation. Force sensors located in the thumb of the prosthesis measure contact and pressure applied to an object while grasping. This information is transmitted to the patients’ nerves leading to their brains. Patients can thus feel when they are touching an object, its characteristics, and how hard they are pressing it, which is crucial for imitating a biological hand.

“Currently, the sensors are not the obstacle for restoring sensation,” says Max Ortiz Catalan. “The challenge is creating neural interfaces that can seamlessly transmit large amounts of artificially collected information to the nervous system, in a way that the user can experience sensations naturally and effortlessly.”
The implantation of this new technology took place at Sahlgrenska University Hospital, led by Professor Rickard Brånemark and Doctor Paolo Sassu. Over a million people worldwide suffer from limb loss, and the end goal for the research team, in collaboration with Integrum AB, is to develop a widely available product suitable for as many of these people as possible.

“Right now, patients in Sweden are participating in the clinical validation of this new prosthetic technology for arm amputation,” says Max Ortiz Catalan. “We expect this system to become available outside Sweden within a couple of years, and we are also making considerable progress with a similar technology for leg prostheses, which we plan to implant in a first patient later this year.”

More about: How the technology works:

The implant system for the arm prosthesis is called e-OPRA and is based on the OPRA implant system created by Integrum AB. The implant system anchors the prosthesis to the skeleton in the stump of the amputated limb, through a process called osseointegration (osseo = bone). Electrodes are implanted in muscles and nerves inside the amputation stump, and the e-OPRA system sends signals in both directions between the prosthesis and the brain, just like in a biological arm.

The prosthesis is mind-controlled, via the electrical muscle and nerve signals sent through the arm stump and captured by the electrodes. The signals are passed into the implant, which goes through the skin and connects to the prosthesis. The signals are then interpreted by an embedded control system developed by the researchers. The control system is small enough to fit inside the prosthesis and it processes the signals using sophisticated artificial intelligence algorithms, resulting in control signals for the prosthetic hand’s movements.

The touch sensations arise from force sensors in the prosthetic thumb. The signals from the sensors are converted by the control system in the prosthesis into electrical signals which are sent to stimulate a nerve in the arm stump. The nerve leads to the brain, which then perceives the pressure levels against the hand.

The neuromusculoskeletal implant can connect to any commercially available arm prosthesis, allowing them to operate more effectively.

More about: How the artificial sensation is experienced:

People who lose an arm or leg often experience phantom sensations, as if the missing body part remains although not physically present. When the force sensors in the prosthetic thumb react, the patients in the study feel that the sensation comes from their phantom hand. Precisely where on the phantom hand varies between patients, depending on which nerves in the stump receive the signals. The lowest level of pressure can be compared to touching the skin with the tip of a pencil. As the pressure increases, the feeling becomes stronger and increasingly ‘electric’.

I have read elsewhere that one of the most difficult aspects of dealing with a prosthetic is the loss of touch. This has to be exciting news for a lot of people. Here’s a link to and a citation for the paper,

Self-Contained Neuromusculoskeletal Arm Prostheses by Max Ortiz-Catalan, Enzo Mastinu, Paolo Sassu, Oskar Aszmann, and Rickard Brånemark. N Engl J Med 2020; 382:1732-1738 DOI: 10.1056/NEJMoa1917537 Published: April 30, 2020

This paper is behind a paywall.

Man with world’s first implanted bionic arm participates in first Cybathlon (olympics for cyborgs)

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The world’s first Cybathlon is being held on Oct. 8, 2016 in Zurich, Switzerland. One of the participants is an individual who took part in some groundbreaking research into implants which was featured in my Oct. 10, 2014 posting. There’s more about the Cybathlon and the participant in an Oct. 4, 2016 news item on phys.org,

A few years ago, a patient was implanted with a bionic arm for the first time in the world using control technology developed at Chalmers University of Technology. He is now taking part in Cybathlon, a new international competition in which 74 participants with physical disabilities will compete against each other, using the latest robotic prostheses and other assistive technologies – a sort of ‘Cyborg Olympics’.

The Paralympics will now be followed by the Cybathlon, which takes place in Zürich on October 8th [2016]. This is the first major competition to show that the boundaries between human and machine are becoming more and more blurred. The participants will compete in six different disciplines using the machines they are connected to as well as possible.

Cybathlon is intended to drive forward the development of prostheses and other types of assistive aids. Today, such technologies are often highly advanced technically, but provide limited value in everyday life.

An Oct. 4, 2016 Chalmers University of Technology press release by Johanna Wilde, which originated the news item, provides details about the competitor, his prosthetic device, and more,

Magnus, one of the participants, has now had his biomechatronically integrated arm prosthesis for almost four years. He says that his life has totally changed since the implantation, which was performed by Dr Rickard Brånemark, associate professor at Sahlgrenska University Hospital.

“I don’t feel handicapped since I got this arm”, says Magnus. “I can now work full time and can perform all the tasks in both my job and my family life. The prosthesis doesn’t feel like a machine, but more like my own arm.”

Magnus lives in northern Sweden and works as a lorry driver. He regularly visits Gothenburg in southern Sweden and carries out tests with researcher Max Ortiz Catalan, assistant professor at Chalmers University of Technology, who has been in charge of developing the technology and leads the team competing in the Cybathlon.

“This is a completely new research field in which we have managed to directly connect the artificial limb to the skeleton, nerves and muscles,” says Dr Max Ortiz Catalan. “In addition, we are including direct neural sensory feedback in the prosthetic arm so the patient can intuitively feel with it.”

Today Magnus can feel varying levels of pressure in his artificial hand, something which is necessary to instinctively grip an object firmly enough. He is unique in the world in having a permanent sensory connection between the prosthesis and his nervous system, working outside laboratory conditions. Work is now under way to add more types of sensations.

At the Cybathlon he will be competing for the Swedish team, which is formed by Chalmers University of Technology, Sahlgrenska University Hospital and the company Integrum AB.

The competition has a separate discipline for arm prostheses. In this discipline Magnus has to complete a course made up of six different stations at which the prosthesis will be put to the test. For example, he has to open a can with a can opener, load a tray with crockery and open a door with the tray in his hand. The events at the Cybathlon are designed to be spectator-friendly while being based on various operations that the participants have to cope with in their daily lives.

“However, the competition will not really show the unique advantages of our technology, such as the sense of touch and the bone-anchored attachment which makes the prosthesis comfortable enough to wear all day,” says Max Ortiz Catalan.

Magnus is the only participant with an amputation above the elbow. This naturally makes the competition more difficult for him than for the others, who have a natural elbow joint.

“From a competitive perspective Cybathlon is far from ideal to demonstrate clinically viable technology,” says Max Ortiz Catalan. “But it is a major and important event in the human-machine interface field in which we would like to showcase our technology. Unlike several of the other participants, Magnus will compete in the event using the same technology he uses in his everyday life.”

Facts about Cybathlon
•    The very first Cybathlon is being organised by the Swiss university ETH Zürich.
•    The €5 million event will take place in Zürich´s 7600 spectator ice hockey stadium, Swiss Arena.
•    74 participants are competing for 59 different teams from 25 countries around the world. In total, the teams consist of about 300 scientists, engineers, support staff and competitors.
•    The teams range from small ad hoc teams to the world’s largest manufacturers of advanced prostheses.
•    The majority of the teams are groups from research labs and many of the prostheses have come straight out of the lab.
•    Unlike the Olympics and Paralympics, the Cybathlon participants are not athletes but ordinary people with various disabilities. The aims of the competition are to establish a dialogue between academia and industry, to facilitate discussion between technology developers and people with disabilities and to promote the use of robotic assistive aids to the general public.
•    Cybathlon will return in 2020, as a seven-day event in Tokyo, to coincide with the Olympics.

Facts about the Swedish team
The Opra Osseointegration team is a multidisciplinary team comprising technical and medical partners. The team is led by Dr Max Ortiz Catalan, assistant professor at Chalmers University of Technology, who has been in charge of developing the technology in close collaboration with Dr Rickard Brånemark, who is a surgeon at Sahlgrenska University Hospital and an associate professor at Gothenburg University. Dr Brånemark led the team performing the implantation of the device. Integrum AB, a Swedish company, complements the team as the pioneering provider of bone-anchored limb prostheses.

This video gives you an idea of what it’s in store on Oct. 8, 2016,

A use for fullerenes—inside insulation plastic for high-voltage cables

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A Jan. 27, 2015 news item on Nanowerk, describes research which suggests that there may a new use for buckminsterfullerenes (or what they’re calling ‘carbon nanoballs’),

Researchers at Chalmers University of Technology [Sweden] have discovered that the insulation plastic used in high-voltage cables can withstand a 26 per cent higher voltage if nanometer-sized carbon balls are added. This could result in enormous efficiency gains in the power grids of the future, which are needed to achieve a sustainable energy system.

The renewable energy sources of tomorrow will often be found far away from the end user. Wind turbines, for example, are most effective when placed out at sea. Solar energy will have the greatest impact on the European energy system if focus is on transport of solar power from North Africa and Southern Europe to Northern Europe.

“Reducing energy losses during electric power transmission is one of the most important factors for the energy systems of the future,” says Chalmers researcher Christian Müller. “The other two are development of renewable energy sources and technologies for energy storage.”

The Jan. 27, 2015 Chalmers University of Technology press release (also on EurekAlert) by Johanna Wilde, which originated the news item, provides more information about the research,

Together with colleagues from Chalmers and the company Borealis in Stenungsund, he [Müller] has found a powerful method for reducing energy losses in alternating current cables.  The results were recently published in Advanced Materials, a highly ranked scientific journal.

The researchers have shown that different variants of the C60 carbon ball, a nanomaterial in the fullerene molecular group, provide strong protection against breakdown of the insulation plastic used in high-voltage cables. Today the voltage in the cables has to be limited to prevent the insulation layer from getting damaged. The higher the voltage the more electrons can leak out into the insulation material, a process which leads to breakdown.

It is sufficient to add very small amounts of fullerene to the insulation plastic for it to withstand a voltage that is 26 per cent higher, without the material breaking down, than the voltage that plastic without the additive can withstand.

“Being able to increase the voltage to this extent would result in enormous efficiency gains in power transmission all over the world,” says Christian Müller. “A major issue in the industry is how transmission efficiency can be improved without making the power cables thicker, since they are already very heavy and difficult to handle.”

Using additives to protect the insulation plastic has been a known concept since the 1970s, but until now it has been unknown exactly what and how much to add. Consequently, additives are currently not used at all for the purpose, and the insulation material is manufactured with the highest possible degree of chemical purity.

In recent years, other researchers have experimented with fullerenes in the electrically conductive parts of high-voltage cables. Until now, though, it has been unknown that the substance can be beneficial for the insulation material.

The Chalmers researchers have now demonstrated that fullerenes are the best voltage stabilizers identified for insulation plastic thus far. This means they have a hitherto unsurpassed ability to capture electrons and thus protect other molecules from being destroyed by the electrons.

To arrive at these findings, the researchers tested a number of molecules that are also used within organic solar cell research at Chalmers. The molecules were tested using several different methods, and were added to pieces of insulation plastic used for high-voltage cables. The pieces of plastic were then subjected to an increasing electric field until they crackled. Fullerenes turned out to be the type of additive that most effectively protects the insulation plastic.

The press release includes some facts about buckyballs or buckminsterfullerenes or fullerenes or C60 or carbon nanoballs, depending on what you want to call them,

 Facts: Carbon ball C60

  • The C60 carbon ball is also called buckminsterfullerene. It consists of 60 carbon atoms that are placed so that the molecule resembles a nanometer-sized football. C60 is included in the fullerene molecular class.
  • Fullerenes were discovered in 1985, which resulted in the Nobel Prize in Chemistry in 1996. They have unique electronic qualities and have been regarded as very promising material for several applications. Thus far, however, there have been few industrial usage areas.
  • Fullerenes are one of the five forms of pure carbon that exist. The other four are graphite, graphene/carbon nanotubes, diamond and amorphous carbon, for example soot.

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

A New Application Area for Fullerenes: Voltage Stabilizers for Power Cable Insulation by Markus Jarvid, Anette Johansson, Renee Kroon, Jonas M. Bjuggren, Harald Wutzel, Villgot Englund, Stanislaw Gubanski, Mats R. Andersson, and Christian Müller. Advanced Materials DOI: 10.1002/adma.201404306 Article first published online: 12 DEC 2014

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Here’s an image of wind turbines, an example of equipment which could benefit greatly from better insulation.,

Images: Lina Bertling, Jan-Olof Yxell, Carolina Eek Jaworski, Anette Johansson, Markus Jarvid, Christian Müller

Images: Lina Bertling, Jan-Olof Yxell, Carolina Eek Jaworski, Anette Johansson, Markus Jarvid, Christian Müller

You can find this image and others by clicking on the Chalmers University press release link (assuming the page hasn’t been moved). You can find more information about Borealis (the company Müller is working with) here.