Articles from April 2021



Animal Muscle Tissue to Move Robots

The US Army Research Laboratory believes its bots could use real muscle, which allows most living things to move and manipulate their environments, instead of mechanical arms, wheels, tracks, and other systems to travel across the battlefield. The concept, which some might find disturbing, is an example of the new field of “biohybrids.”  Today’s military robots, particularly ground-based robots, navigate the battlefield on wheels and tracks, methods of locomotion copied over from human-occupied vehicles.

But researchers “are reaching a point where they’re experiencing diminishing returns in the design of these robots with wheels as their primary locomotor, and batteries as their centralized power system,” NextGov reports. Modern army robots use batteries that power motors, which then drive axles and turn wheels. A biohybrid-powered robot would replace this entire system with lab-grown organic muscle tissue that might power artificial legs or other limbs. Electrical impulses or chemical actuation would control the muscles.

One of the major advantages of using organic muscle tissue is its inherent flexibility. Muscles and tendons can flex, pull, and give as an animal moves over mixed terrain, and especially as it encounters unexpected problems.

Dr. Dean Culver, a research scientist at the Army Research Lab, explains it like this, via NextGov:

If you run through a field, and your foot steps into a rabbit hole, even before the signal from your foot has reached your brain to say, ‘Oh, my gosh, I’m in a rabbit hole,’ your body is already moving to accommodate that sudden change. Part of that is the way that control systems are designed in organisms—that’s obviously really amazing—but another part of that is the ability of muscles and tendons to bend and flex a little bit, and offer those control systems an opportunity to adapt. So that is a huge capability that we could offer.”

A wheel-bound robot can’t do that, instead relying on shock absorbers to make up for the sudden shift.  “Robots who are, obviously, in Army applications going to go into unknown and unpredictable environments—they need to be able to adapt to things that they weren’t planning for,” Culver said. “So, that’s a big part of this effort as well.”

Source: https://www.popularmechanics.com/

COVID-19 Can Cause Antibodies that Mistakenly Target your Own Tissues

An increasing body of research is pointing toward the possibility that COVID-19 causes the development of autoantibodies linked to other autoimmune diseases — and may be tied to the long-hauler symptoms associated with coronavirus.

In the latest preprint study (which means it has not yet undergone peer review) researchers analyzed the levels of 18 different autoantibodies between four groups:

  • 29 unexposed pre-pandemic individuals from the general population
  • 20 individuals hospitalized with moderate-to-severe COVID-19
  • 9 recovering COVID-19-infected individuals with asymptomatic to mild viral symptoms during the acute phase, with samples collected between 1.8 and 7.3 months after infection
  • 6 unexposed pre-pandemic subjects with lupus (an autoimmune disease that involves different kinds of autoantibodies)
  • Autoantibodies are antibodies that mistakenly target your own tissues or organs and are associated with diseases such as rheumatoid arthritis and lupus. Unsurprisingly, the researchers found that autoantibodies were detected in five out of the six lupus subjects, compared to just 11 of 29 non-lupus, pre-pandemic controls.

However, the researchers also found that autoantibodies were detected in seven out of nine patients recovering from SARS-CoV-2 and in 12 out of the 20 hospitalized individuals with moderate to severe COVID-19. In the first group, autoantibodies were detected in all patients with reported persistent symptoms and two of the four without any long-term symptoms.

The autoantibodies that set SARS-CoV-2  infected patients apart from the pre-pandemic subjects are widely associated with myopathies (neuromuscular disorders), vasculitis (inflammation of the blood vessels), and antiphospholipid syndromes (when your body creates antibodies that make your blood much more likely to clot), all of which are conditions that share some similarities with COVID-19. The researchers note that these results underscore the importance of further investigating autoimmunity during a COVID-19 infection, and the role of autoimmunity in lingering symptoms. That said, they do urge caution in interpreting the results, which still need to undergo peer review.

It’s a signal; it is not definitive,” lead researcher Nahid Bhadelia, MD, told the New York Times. We don’t know how prevalent it is, and whether or not it can be linked to long COVID.” (Long COVID is sometimes used to describe the syndrome that causes long-hauler symptoms in those who have recovered from COVID-19.)

Still, as many as one-third of COVID-19 survivors say they still experience symptoms — and determining the role autoimmunity may play after coronavirus infection is critical.

This is a real phenomenon,” Dr. Bhadelia said. “We’re looking at a second pandemic of people with ongoing potential disability who may not be able to return to work, and that’s a huge impact on the health symptoms.”

Source: https://creakyjoints.org/
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https://www.medrxiv.org/

Skin and Bones Repaired by Bioprinting

Fixing traumatic injuries to the skin and bones of the face and skull is difficult because of the many layers of different types of tissues involved, but now, researchers have repaired such defects in a rat model using bioprinting during surgery, and their work may lead to faster and better methods of healing skin and bones.

Schematic of the skin and bone bioprinting process. After scanning, the bone and then skin layers are bioprinted creating a layered repair with bone, a barrier layer, and dermis and epidermis

This work is clinically significant,” said Ibrahim T. Ozbolat, Associate Professor of Biomedical Engineering and Neurosurgery, Penn State. “Dealing with composite defects, fixing hard and soft tissues at once, is difficult. And for the craniofacial area, the results have to be esthetically pleasing.

Currently, fixing a hole in the skull involving both bone and soft tissue requires  using bone from another part of the patient’s body or a cadaver. The bone must be covered by soft tissue with blood flow, also harvested from somewhere else, or the bone will die. Then surgeons need to repair the soft tissue and skin. Ozbolat and his team used extrusion bioprinting and droplet bioprinting of mixtures of cells and carrier materials to print both bone and soft tissueThere is no surgical method for repairing soft and hard tissue at once,” said Ozbolat. “This is why we aimed to demonstrate a technology where we can reconstruct the whole defect — bone to epidermis — at once.”

The researchers attacked the problem of bone replacement first, beginning in the laboratory and moving to an animal model. They needed something that was printable and nontoxic and could repair a 5-millimeter hole in the skull. The “hard tissue ink” consisted of collagen, chitosan, nano-hydroxyapatite and other compounds and mesenchymal stem cells — multipotent cells found in bone marrow that create bone, cartilage and bone marrow fat. The hard tissue ink extrudes at room temperature but heats up to body temperature when applied. This creates physical cross-linkage of the collagen and other portions of the ink without any chemical changes or the necessity of a crosslinker additive.

The researchers used droplet printing to create the soft tissue with thinner layers than the bone. They used collagen and fibrinogen in alternating layers with crosslinking and growth enhancing compounds. Each layer of skin including the epidermis and dermis differs, so the bioprinted soft tissue layers differed in composition. Experiments repairing 6 mm holes in full thickness skin proved successful. Once the team understood skin and bone separately, they moved on to repairing both during the same surgical procedure. “This approach was an extremely challenging process and we actually spent a lot of time finding the right material for bone, skin and the right bioprinting techniques,” said Ozbolat.

The scientists have reported their results in Advanced Functional Materials.

Source: https://news.psu.edu/

Simple test Improves Prostate Cancer Detection

A new urine-based test improved prostate cancer detection — including detecting more aggressive forms of prostate cancer — compared with traditional models based on prostate serum antigen — or PSA — levels, a new study finds. The test, developed at the U-M Comprehensive Cancer Center (University of Michigan), is called Mi-Prostate Score, or MiPS. It combines PSA with two markers for prostate cancer, T2:ERG and PCA3, both of which can be detected through a urine sample. The test has been available clinically since September 2013.

Around 50 percent of men who undergo a prostate biopsy will not have cancer. We need better ways to manage elevated PSA and determine who really needs to have a biopsy. MiPS gives men and their doctors better information to help make those decisions,” says lead study author Dr. Scott A. Tomlins, assistant professor of pathology and urology at the Medical School.

The study looked at 1,977 men undergoing prostate biopsy because of elevated PSA levels. Using urine samples, the researchers conducted MiPS testing and compared results to various combinations of PSA, PCA3, T2:ERG and other PSA-based risk calculators. They assessed how well the individual biomarkers and combinations of biomarkers predicted the likelihood of cancer and the likelihood of high-risk cancer — the aggressive type that needs immediate treatment.

The test reports individual risk estimates for prostate cancer and high-grade cancer. Each patient’s personal threshold for choosing to undergo biopsy may vary, so there is no single cutoff for a “positive” result. However, using one MiPS cutoff score to decide whether to biopsy patients would reduce the number of biopsies by one-third, while delaying the diagnosis of only about 1 percent of high-risk prostate cancers.

MiPS gives men a more individualized risk assessment for prostate cancer, so that men concerned about their serum PSA levels can have a more informed conversation with their doctor about next steps in their care,” Tomlins says. A cost-benefit analysis of MiPS is being conducted. PCA3 is approved by the U.S. Food and Drug Administration for prostate cancer risk assessment in men with a previous negative biopsy. Most of the men involved in this study were undergoing initial biopsy, suggesting MiPS can be useful earlier in the process.

The study is published in European Urology.

Source: https://record.umich.edu/

Reversible Gene Editing

The gene-editing system, CRISPR-Cas9, is truly revolutionizing medicine: in the future, it may help us eradicate ailments from sickle cell, cancer, and even blindness. While this system allows scientists to make changes to DNA, the changes are permanent. On the one hand, this is useful, because it could potentially cure genetic diseases without requiring a lifetime of treatment. The downside is that unintended consequences of the edits are difficult to fix — especially “off-targetedits, where CRISPR changes the wrong stretch of DNA. This is a huge concern for the scientific community — no one wants to be responsible for genetic mutations that go awry.

But what if the changes were not permanent? What if we could simply turn CRISPR off whenever we wanted?  A team of researchers at MIT and UCSF has developed a new gene-editing system that they call “CRISPRoff.” According to the researchers, this system can change how specific genes behave, much like CRISPR, while leaving the DNA strand unaltered — and even better, these modifications are completely reversible.

The traditional CRISPR system invented in 2012 relies on a protein called Cas9, which is found in bacterial immune systems. Cas9 can target specific genes and cut the DNA strand, removing or replacing defective genes. The DNA then self-repairs and continues functioning after the gene has been removed. Because this system alters the DNA sequence, the changes are permanent, and even though CRISPR is one of the most accurate ways to change DNA, it can be difficult to ensure that the modification will always be limited to that one gene.

As beautiful as CRISPR-Cas9 is, it hands off the repair to natural cellular processes, which are complex and multifaceted,MIT‘s Jonathan Weissman and coauthor of the study, said in a press release. “It’s very hard to control the outcomes.”

CRISPRoff is a new kind of gene-editing technology that doesn’t modify the DNA sequence, but instead changes the way those sequences are read. With this system, scientists can silence or activate various genes by adding chemical tags onto the DNA strand, without making any permanent changes. The tags cause the DNA to become unreadable by the cell’s messenger RNA, the molecule responsible for carrying instructions from the DNA to make proteins.

Source: https://news.mit.edu/

How to Speed up Bone Implant Recovery

An international research team led by Monash University has uncovered a new technique that could speed up recovery from bone replacements by altering the shape and nucleus of individual stem cells. The research collaboration involving Monash University, the Melbourne Centre for Nanofabrication, CSIRO, the Max Planck Institute for Medical Research and the Swiss Federal Institute of Technology in Lausanne, developed micropillar arrays using UV nanoimprint lithography that essentially ‘trick’ the cells to become boneNanoimprint lithography allows for the creation of microscale patterns with low cost, high throughput and high resolution.

When implanted into the body as part of a bone replacement procedure, such as a hip or knee, researchers found these pillars – which are 10 times smaller than the width of a human hair – changed the shape, nucleus and genetic material inside stem cells. Not only was the research team able to define the topography of the pillar sizes and the effects it had on stem cells, but they discovered four times as much bone could be produced compared to current methods.

Novel micropillars, 10 times smaller than the width of a human hair, can change the size, shape and nucleus of individual stem cells and ‘trick’ them to become bone

What this means is, with further testing, we can speed up the process of locking bone replacements with surrounding tissue, in addition to reducing the risks of infection,” Associate Professor Jessica Frith from Monash University’s Department of Materials Science and Engineering said. “We’ve also been able to determine what form these pillar structures take and what size they need to be in order to facilitate the changes to each stem cell, and select one that works best for the application.

Researchers are now advancing this study into animal model testing to see how they perform on medical implants. Engineers, scientists and medical professionals have known for some time that cells can take complex mechanical cues from the microenvironment, which in turn influences their development.

However, Dr Victor Cadarso from Monash University’s Department of Mechanical and Aerospace Engineering says their results point to a previously undefined mechanism where ‘mechanotransductory signalling’ can be harnessed using microtopographies for future clinical settings. “Harnessing surface microtopography instead of biological factor supplementation to direct cell fate has far-reaching ramifications for smart cell cultureware in stem cell technologies and cell therapy, as well as for the design of smart implant materials with enhanced osteo-inductive capacity,” Dr Cadarso said.

The findings were published in Advanced Science.

Source: https://www.monash.edu/

Self-Assembling Nanofibers Prevent Damage from Inflammation

Biomedical engineers at Duke University have developed a self-assembling nanomaterial that can help limit damage caused by inflammatory diseases by activating key cells in the immune system. In mouse models of psoriasis, the nanofiber-based drug has been shown to mitigate damaging inflammation as effectively as a gold-standard therapy. One of the hallmarks of inflammatory diseases, like rheumatoid arthritis, Crohn’s disease and psoriasis, is the overproduction of signaling proteins, called cytokines, that cause inflammation. One of the most significant inflammatory cytokines is a protein called TNF. Currently, the best treatment for these diseases involves the use of manufactured antibodies, called monoclonal antibodies, which are designed to target and destroy TNF and reduce inflammation.

Although monoclonal antibodies have enabled better treatment of inflammatory diseases, the therapy is not without its drawbacks, including a high cost and the need for patients to regularly inject themselves. Most significantly, the drugs also have uneven efficacy, as they may sometimes not work at all or eventually stop working as the body learns to make antibodies that can destroy the manufactured drug. To circumvent these issues, researchers have been exploring how immunotherapies can help teach the immune system how to generate its own therapeutic antibodies that can specifically limit inflammation.

The graphic shows the peptide nanofiber bearing complement protein C3dg (blue) and key components of the TNF protein, which include B-cell epitopes (green), and T-cell epitopes (purple)

We’re essentially looking for ways to use nanomaterials to induce the body’s immune system to become an anti-inflammatory antibody factory,” said Joel Collier, a professor of biomedical engineering at Duke University. “If these therapies are successful, patients need fewer doses of the therapy, which would ideally improve patient compliance and tolerance. It would be a whole new way of treating inflammatory disease.”

In their new paper, which appeared online in the Proceedings of the National Academy of Sciences (PNAS), Collier and Kelly Hainline, a graduate student in the Collier lab, describe how novel nanomaterials could assemble into long nanofibers that include a specialized protein, called C3dg. These fibers then were able to activate immune system B-cells to generate antibodies. “C3dg is a protein that you’d normally find in your body,” said Hainline. “The protein helps the innate immune system and the adaptive immune system communicate, so it can activate specific white blood cells and antibodies to clear out damaged cells and destroy antigens.”

Due to the protein’s ability to interface between different cells in the immune system and activate the creation of antibodies without causing inflammation, researchers have been exploring how C3dg could be used as a vaccine adjuvant, which is a protein that can help boost the immune response to a desired target or pathogen.

Source: https://pratt.duke.edu/

How to Convert Carbon Dioxide (CO2) into Fuels

If the CO2 content of the atmosphere is not to increase any further, carbon dioxide must be converted into something else. However, as CO2 is a very stable molecule, this can only be done with the help of special catalysts. The main problem with such catalysts has so far been their lack of stability: after a certain time, many materials lose their catalytic properties.

At TU Wien (Austria), research is being conducted on a special class of minerals – the perovskites, which have so far been used for solar cells, as anode materials or electronic components rather than for their catalytic properties. Now scientists at TU Wien have succeeded in producing a special perovskite that is excellently suited as a catalyst for converting CO2 into other useful substances, such as synthetic fuels. The new perovskite catalyst is very stable and also relatively cheap, so it would be suitable for industrial use.

We are interested in the so-called reverse water-gas shift reaction,” says Prof. Christoph Rameshan from the Institute of Materials Chemistry at TU Wien. “In this process, carbon dioxide and hydrogen are converted into water and carbon monoxide. You can then process the carbon monoxide further, for example into methanol, other chemical base materials or even into fuel.”

This reaction is not new, but it has not really been implemented on an industrial scale for CO2 utilisation. It takes place at high temperatures, which contributes to the fact that catalysts quickly break down. This is a particular problem when it comes to expensive materials, such as those containing rare metals.

Christoph Rameshan and his team investigated how to tailor a material from the class of perovskites specifically for this reaction, and he was successful: “We tried out a few things and finally came up with a perovskite made of cobalt, iron, calcium and neodymium that has excellent properties,” says Rameshan.

Because of its crystal structure, the perovskite allows certain atoms to migrate through it. For example, during catalysis, cobalt atoms from the inside of the material travel towards the surface and form tiny nanoparticles there, which are then particularly chemically active. At the same time, so-called oxygen vacancies form – positions in the crystal where an oxygen atom should actually sit. It is precisely at these vacant positions that CO2 molecules can dock particularly well, in order to then be dissociated into oxygen and carbon monoxide.

We were able to show that our perovskite is significantly more stable than other catalysts,” says Christoph Rameshan. “It also has the advantage that it can be regenerated: If its catalytic activity does wane after a certain time, you can simply restore it to its original state with the help of oxygen and continue to use it.

Initial assessments show that the catalyst is also economically promising. “It is more expensive than other catalysts, but only by about a factor of three, and it is much more durable,” says Rameshan. “We would now like to try to replace the neodymium with something else, which could reduce the cost even further.“Theoretically, you could use such technologies to get CO2 out of the atmosphere – but to do that you would first have to concentrate the carbon dioxide, and that requires a considerable amount of energy. It is therefore more efficient to first convert CO2 where it is produced in large quantities, such as in industrial plants. “You could simply add an additional reactor to existing plants that currently emit a lot of CO2, in which the CO2 is first converted into CO and then processed further,” says Christoph Rameshan. Instead of harming the climate, such an industrial plant would then generate additional benefits.

Source: https://www.tuwien.at/

How to Completely Wipe out Colon Cancer in Anybody Who Gets Screened

Michael Wallace has performed hundreds of colonoscopies in his 20 years as a gastroenterologist. He thinks he’s pretty good at recognizing the growths, or polyps, that can spring up along the ridges of the colon and potentially turn into cancer. But he isn’t always perfect. Sometimes the polyps are flat and hard to see. Other times, doctors just miss them. “We’re all humans,” says Wallace, who works at the Mayo Clinic. After a morning of back-to-back procedures that require attention to minute details, he says, “we get tired.”

Colonoscopies, if unpleasant, are highly effective at sussing out pre-cancerous polyps and preventing colon cancer. But the effectiveness of the procedure rests heavily on the abilities of the physician performing it. Now, the Food and Drug Administration has approved a new tool that promises to help doctors recognize precancerous growths during a colonoscopy: an artificial intelligence system made by Medtronic. Doctors say that alongside other measures, the tool could help improve diagnoses.

 

We really have the opportunity to completely wipe out colon cancer in anybody who gets screened,” says Wallace, who consulted with Medtronic on the project.

The Medtronic system, called GI Genius, has seen the inside of more colons than most doctors. Medtronic and partner Cosmo Pharmaceuticals trained the algorithm to recognize polyps by reviewing more than 13 million videos of colonoscopies conducted in Europe and the US that Cosmo had collected while running drug trials. To “teach” the AI to distinguish potentially dangerous growths, the images were labeled by gastroenterologists as either normal or unhealthy tissue. Then the AI was tested on progressively harder-to-recognize polyps, starting with colonoscopies that were performed under perfect conditions and moving to more difficult challenges, like distinguishing a polyp that was very small, only in range of the camera briefly, or hidden in a dark spot. The system, which can be added to the scopes that doctors already use to perform a colonoscopy, follows along as the doctor probes the colon, highlighting potential polyps with a green box. GI Genius was approved in Europe in October 2019 and is the first AI cleared by the FDA for helping detect colorectal polyps. “It found things that even I missed,” says Wallace, who co-authored the first validation study of GI Genius. “It’s an impressive system.”

Source: https://www.wired.com/

How to Produce Drinkable Water from Sea Water

University of California, Berkeley, chemists have discovered a way to simplify the removal of toxic metals, like mercury and boron, during desalination to produce clean water, while at the same time potentially capturing valuable metals, such as gold.

Desalination — the removal of salt — is only one step in the process of producing drinkable water, or water for agriculture or industry, from ocean or waste water. Either before or after the removal of salt, the water often has to be treated to remove boron, which is toxic to plants, and heavy metals like arsenic and mercury, which are toxic to humans. Often, the process leaves behind a toxic brine that can be difficult to dispose of.

The new technique, which can easily be added to current membrane-based electrodialysis desalination processes, removes nearly 100% of these toxic metals, producing a pure brine along with pure water and isolating the valuable metals for later use or disposal.

A flexible polymer membrane incorporating nanoparticles of PAF selectively absorbs nearly 100% of metals such mercury, copper or iron during desalination, more efficiently producing clean, safe water

Desalination or water treatment plants typically require a long series of high-cost, pre- and post-treatment systems that all the water has to go through, one by one,” said Adam Uliana, a UC Berkeley graduate student who is first author of a paper describing the technology. “But here, we have the ability to do several of these steps all in one, which is a more efficient process. Basically, you could implement it in existing setups.”

The UC Berkeley chemists synthesized flexible polymer membranes, like those currently used in membrane separation processes, but embedded nanoparticles that can be tuned to absorb specific metal ionsgold or uranium ions, for example. The membrane can incorporate a single type of tuned nanoparticle, if the metal is to be recovered, or several different types, each tuned to absorb a different metal or ionic compound, if multiple contaminants need to be removed in one step.

The polymer membrane laced with nanoparticles is very stable in water and at high heat, which is not true of many other types of absorbers, including most metal-organic frameworks (MOFs), when embedded in membranes.

Source: https://news.berkeley.edu/