Category: Medical Research & Technology

Categories : Medical Research & Technology NeurologyTags :

Brain-computer Interface Lets Paralysed People Write Letters

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Image by Gerd Altmann from Pixabay

Researchers have developed a new brain-computer interface (BCI) that can let paralysed people write by mentally writing letters by hand.

Working with a participant with paralysis who has sensors implanted in his brain, the team used an algorithm to identify letters in real time as he attempted to write them, putting the results on a screen.

This technology could be further developed to allow people with paralysis type rapidly without using their hands, said study coauthor Krishna Shenoy, a Howard Hughes Medical Institute Investigator at Stanford University who jointly supervised the work with Jaimie Henderson, a Stanford neurosurgeon.

By attempting handwriting, the study participant was able to ‘type’ 90 characters per minute — more than double the previous record for typing with such a brain-computer interface.

Thought-powered communication

Even if injury or disease the ability to move, the brain’s neural activity for being able to do so remains. By making use of this activity, researchers can help people with paralysis or amputations regain lost abilities.

In recent years, Shenoy’s team has decoded the neural activity associated with speech in the hopes of reproducing it. Patients with implanted sensors mentally pointed at and clicked on letters on a screen to type at about 40 characters per minute, the previous speed record for typing with a BCI.
Wanting to try something new and different, Frank Willett, a neuroscientist in Shenoy’s group, wondered if it might be possible to harness the brain signals evoked by writing by hand “We want to find new ways of letting people communicate faster,” he said. 

The team worked with a participant enrolled in a clinical trial involving BCIs. Henderson implanted two tiny sensors into the part of the brain that controls the hand and arm, making it possible for the person to, for example, move a robotic arm or a cursor on a screen by attempting to move their own paralysed arm.
The participant, who was 65 years old at the time of the research, had a spinal cord injury that left him paralysed from the neck down. A machine learning algorithm recognised the patterns his brain produced when he attempted to write each letter.

With this system, the man could copy sentences and answer questions at a rate similar to that of someone his age typing on a smartphone. The reason why this so-called “Brain-to-Text” BCI is so fast is because each letter elicits a highly distinctive activity pattern, making it relatively easy for the algorithm to distinguish one from another, Willett explained.

A new system

Shenoy’s team envisions using attempted handwriting for text entry as part of a more comprehensive system that also includes point-and-click navigation, much like that used on current smartphones, and even attempted speech decoding. “Having those two or three modes and switching between them is something we naturally do,” he said.
The team intends to next work with a participant who cannot speak, such as a person with amyotrophic lateral sclerosis, a degenerative neurological disorder leading to loss of movement and speech.

The new system could potentially help those suffering from paralysis caused by a number of conditions, Henderson added. Those include brain stem stroke, which afflicted Jean-Dominique Bauby, the author of the book The Diving Bell and the Butterfly. “He was able to write this moving and beautiful book by selecting characters painstakingly, one at a time, using eye movement,” Henderson said. “Imagine what he could have done with Frank’s handwriting interface!”

Source: Howard Hughes Medical Institute

Categories : Medical Research & Technology Mental HealthTags :

Distraction a Big Problem in Teletherapy Sessions

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Photo by Tracy le Blanc from Pexels

A small survey has found that although therapists appear to prefer virtual sessions over in-person meetings, a significant proportion admit to being distracted while delivering care.

A third of respondents admitted to providing lower-quality care to clients during online sessions. Overall, 39% admitted to checking emails and social media while providing virtual care.

These were the results of a survey of 600 therapists conducted and published by OnlineTherapy.com, a virtual directory for teletherapists and counselors. It’s also an affiliate of the controversial app BetterHelp, stating on their website that the company “may receive compensation from BetterHelp if you purchase products or services through the links provided.”

Online care is generally well received by therapists: nearly half said they prefer virtual sessions over in-person meetings. They appreciated many advantages of virtual therapy, such as working from home which allows therapists to keep a flexible schedule and increases their availability. Video sessions also provide therapists with a uniquely intimate look into their clients’ daily lives, making assessing their mental health easier.

However, teletherapy has introduced its own challenges. Besides the struggle to remain for therapists to stay focused themselves, 56% of those surveyed said their clients are more easily distracted during virtual sessions, and 48% reported technological issues as a major impediment to their practice.

Peter Yellowlees, MD, of UC Davis Health in Sacramento, California, noted with concern and confusion that 16% of therapists reported substance use before or during their sessions.

“There are all sorts of people in this world who call themselves therapists, most of whom have very reasonable training, but quite a number don’t,” Dr Yellowlees told MedPage Today, expressing serious doubts about whether these rates of social media distraction and substance use during virtual sessions would ring true for mental health clinicians with PhDs and MDs.

According to a spokesperson from OnlineTherapy.com, the survey only asked if respondents were currently practicing mental health professionals and did not ask for their credentials or certifications.

The results of the survey did, however, echo Dr Yellowlees’s own concerns of mental health problems on the rise of among therapists in general. The vast majority (90%) said that during the last year they suffered mental health issues, including anxiety disorders (50%) and depressive disorder (48%). This would likely impact the level of care that a therapist able to provide to their clients.

A further concern is that 17% of respondents reported seriously considered suicide since the start of the pandemic.

But  Dr Yellowlees also sees teletherapy as a way for therapists to start getting the help that they need, rather than simply treating themselves in fear of stigma or possible repercussions for their licences.

“It’s undoubtedly helped significantly,” Dr Yellowlees said. “We know that certain teletherapies are actually good for the mental health of providers, as well as the patients.”

Source: MedPage Today

Categories : Cardiovascular Disease Medical Research & TechnologyTags :

Manganese Sharpens MRI Scans of Heart Attacks

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Clinician prepares an MRI scanner. Image by Michal Jarmoluk from Pixabay

Manganese, a common trace mineral, could improve MRI scans of hearts after a heart attack and guide therapy, according to a new study.

By far the most widely used contrast agent for MRI is gadolinium, which improves the visibility of different organs and tissue types in MRI scans. However, it is taken up equally by cells regardless of their activity, and spreads out in damaged tissue. Furthermore, there are also extremely rare instances of serious kidney damage from its use. 

Manganese, besides being less toxic, has a useful property in that it competes with calcium uptake. Calcium handling is highly sensitive to altered heart muscle viability and changes rapidly after damage. Manganese ions enter heart muscle cells through calcium channels, and thus give a useful surrogate for heart tissue viability.

The contrast agent was tested first in vitro with heart muscle cells, and then in mice which had a myocardial infarction (heart attack) induced. The manganese contrast agent was administered with a calcium supplement or administered slowly to negate the effects of manganese interfering with the heart’s calcium channel. Findings were evaluated by examining the infarct size and blood supply at three key intervals: one hour, one day and 14 days after a myocardial infarction was induced. Overall, the manganese contrast agent was superior to gadolinium.

These findings could have major implications for heart attack treatment, if confirmed. They could also be greatly useful in preclinical evaluation of treatments for patients with cardiac ischaemia – where blood supply to the heart muscle is reduced, possibly leading to cardiac arrest.

Furthermore, if manganese-enhanced MRI is performed within the first few hours of a heart attack it could be used to determine the optimal treatment regime for individual patients – helping to regulate changes in the cardiac muscle and thereby further improving survival chances. 

“Magnetic resonance imaging (MRI) is increasingly used to diagnose and give information on heart conditions,” said lead researcher Dr Patrizia Camelliti, Senior Lecturer in Cardiovascular Science, University of Surrey. “This research using mice allows us to measure the health status of the heart muscle rapidly after a heart attack and could provide important information for optimizing treatments in patients.”

Source: News-Medical.Net

Journal reference: Jasmin, N.H., et al. (2021) Myocardial Viability Imaging using Manganese‐Enhanced MRI in the First Hours after Myocardial Infarction. Advanced Science. doi.org/10.1002/advs.202003987.

Categories : Immunology Medical Research & Technology New Compounds and TreatmentsTags :

New Treatment may Regenerate Liver Scarring

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Japanese researchers have come up with a new approach that could revolutionise the treatment and prevention of liver disease damage and possibly regenerate liver scarring.

This novel strategy involves small extracellular vesicles (sEVs), which are lipid-enclosed particles that are naturally released from a cell. The ones used in this study derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs).

Cirrhosis (scarring of the liver) and other chronic liver diseases result in up to 2 million deaths reported annually around the world, these in turn account for approximately 3.5% of annual deaths globally. As the only treatment for clinically advanced cirrhosis liver transplantation, targeted therapies for modulating fibrosis and aiding tissue regeneration.  The ability to control fibrosis–the growth of fibrous tissue in response to damage– is often lost in livers under advanced cirrhosis.  The research builds upon this.

One of the most popular approaches is cell therapy, where mesenchymal stromal cells (MSCs) and macrophages have shown the potential to reduce liver fibrosis. MSCs are able to transform into a number of different cells. They are cost-effective, being available not only from bone marrow, but also from medical waste such as umbilical cord tissue, adipose (fatty) tissue, and dental pulp.

Apart from the ease of availability, MSCs can also be lab-grown. MSCs don’t replace tissue but instead have been shown to be medical signaling cells that indirectly produce cytokines, chemokines, growth factors, and exosomes that are crucial for repairing and regenerating damaged tissue.

Previous research showed that MSCs have anti-inflammatory, anti-fibrotic, and anti-oxidative effects through these humoural factors. MSCs also have lower potential for provoking an immune response and therefore rejection, enabling their use in both within the same individual and another.

In a series of experimental mice studies, researchers pre-conditioned fat extracellular vesicles with interferon gamma (IFN-γ), an important immune system signaller. They showed that this increases the number of anti-inflammatory macrophages, which are the key players in tissue repair, reducing fibrosis and promoting tissue regeneration.

They reported that both MSCs derived from fatty tissue (AD-MSC-sEVs) and AD-MSC-γ-sEVs can boost macrophage motility and phagocytic activity. In addition, they also show that AD-MSC-γ- sEVs can effectively control inflammation and fibrosis in mice with cirrhosis.

They found thatAD-MSC-derived sEVs can affect the shape and function of macrophages, effectively recruiting them into damaged areas to initiate tissue repair.

In an interview, researcher Dr Atsunori Tsuchiya at Niigata University, explained that, “Both mesenchymal stromal cells and macrophages are reported to have therapeutic effects for liver cirrhosis, however relationship of both cells and mechanisms of action was not clear. We challenged this problem.”

He continued, “We found the important fact that extracellular vesicles from interferon-γ can induce the tissue repair macrophages, which can regress fibrosis and promote liver regeneration effectively.” 

Dr Suguru Takeuchi, another of the researchers at Niigata University, concurred: “In our previous study, we reported that intravenous administration of mesenchymal stromal cells migrated to the lung, can work as ‘conducting cells’ and affect to macrophages ‘working cells’ in the liver.

“In this study we first elucidated that extracellular vesicles from mesenchymal stromal cells are key molecules to affect the macrophages.”

This study, which complements macrophage therapy, holds potential as a strategy for treating liver diseases using small extracellular vesicles pre-conditioned with IFN-γ. However, further development is needed, as well as uncovering the mechanisms by which they increase Treg cell count.

“Our results showed that modified extracellular vesicles can become a new therapeutic strategy for liver cirrhosis,” said Professor Shuji Terai, Niigata University.

Source: News-Medical.Net

Journal information: Takeuchi, S., et al. (2021) Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis. npj Regenerative Medicine. oi.org/10.1038/s41536-021-00132-4.

Categories : Medical Research & TechnologyTags :

A 3D Printed Hydrogel With Self-healing Capacity

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Much research has focused on hydrogels, polymer-based materials containing large amounts of water, but hydrogels with both self-healing and complex construction have proved elusive until now. 

Hydrogels need to fulfil two key criteria if they are to be effective replacements for organic tissue: the ability to form extremely complex shapes, and to self-heal after sustaining damage. Previously, hydrogels created in the laboratory had either the capability of being 3D printed into complex shapes, or had the ability to self-heal. This research realises the first time these two capabilities had been combined into one material.

The development of these materials may now be easier, and cheaper, thanks to the use of 3D printing: the researchers in the MP4MNT (Materials and Processing for Micro and Nanotechnologies) team of the Department of Applied Science and Technology of the Politecnico di Torino, coordinated by Professor Fabrizio Pirri. The researchers detailed their work in the prestigious journal Nature Communications.

In addition, the hydrogel was created using both commercially available materials and printer, thus making the approach proposed extremely flexible and potentially applicable anywhere, throwing open the door for development in the fields of both biomedicine and soft robotics.

The research was carried out in the context of the HYDROPRINT3D doctoral project, funded by the Compagnia di San Paolo, in the frame of “Joint Research Projects with Top Universities” initiative, by the PhD student Matteo Caprioli, under the supervision of the DISAT researcher Ignazio Roppolo, in collaboration with Professor Magdassi’s research group of the Hebrew University of Jerusalem (Israel).
The researchers used the digital pulsed light to create a semi-interpenetrated structure of polymer strands that, when severed, could rejoin in 12 hours at room temperature with no outside intervention. The restored section retains 72% of its initial strength.

“[For] many years, in the MP4MNT group, a research unit coordinated by Dr Annalisa Chiappone and I, specifically devoted to development of new materials that can be processed using 3D printing activated by light,” said Ignazio Roppolo, Researcher, DISAT. “3D printing is able to offer a synergistic effect between the design of the object and the intrinsic properties of materials, making [it] possible to obtain manufactured items with unique features.

“From our perspective, we need to take advantage of this synergy to best develop the capabilities of 3D printing, so that this can truly become an element of our everyday life. And this research falls right in line with this philosophy.”

This research represents a first step towards the development of highly complex devices, which can exploit both the complex geometries and the intrinsic self-healing properties in various application fields. Once biocompatibility studies have been refined, it will be possible to use these structures both for cellular mechanism research and for regenerative medicine applications.

Source: News-Medical.Net

Journal reference: Caprioli, M., et al. (2021) 3D-printed self-healing hydrogels via Digital Light Processing. Nature Communications. doi.org/10.1038/s41467-021-22802-z.

Categories : COVID Medical Research & TechnologyTags :

‘Nanotraps’ Capture COVID Virus and Prevent Infection

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Researchers have developed an entirely new treatment for COVID: ‘Nanotraps’ that capture the viruses inside the body, allowing the immune systems to destroy them

The “Nanotraps” mimick the human cells the virus normally attaches to, and bind it to their surface, keeping the virus from reaching other cells and target it for destruction by the immune system. It is possible that Nanotraps could be used on SARS-CoV-2 variants, and could be administered as a nasal spray.

“Since the pandemic began, our research team has been developing this new way to treat COVID-19,” said Assistant Professor Jun Huang, whose lab led the research. “We have done rigorous testing to prove that these Nanotraps work, and we are excited about their potential.”

Postdoc Min Chen and graduate student Jill Rosenberg targeted the spike mechanism that SARS-CoV-2 uses to lock onto ACE2 proteins on human cells.

To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Other nanoparticles were designed with neutralising antibodies on their surfaces.

ACE2 proteins and neutralising antibodies have both been used in COVID treatments, but by mounting them onto nanoparticles, a much more effective and robust means for trapping the virus was created.

The nanoparticles are smaller than cells, 500 nanometres in diameter, allowing them to reach deep inside tissue and trap the virus.

No evidence of toxicity was seen in tests with mice, and they then tested the Nanotraps against a non-replicating virus called a pseudovirus in human lung cells in tissue culture plates and saw that they completely prevented viral entry into the cells.

 When the nanoparticle binds to the virus (about 10 minutes after injection), it chemically signalled macrophages to engulf and destroy the nanoparticle and the attached virus. Macrophages normally engulf nanoparticles, so this merely sped up the process.

Testing the Nanotraps on a pair of donated lungs kept alive with a ventilator, they found that they completely prevented infection.

They also collaborated with researchers at Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found a 10 times better performance than with neutralising antibodies or ACE2 inhibitor.

The researchers plan further tests, including live virus and its variants.

“That’s what is so powerful about this Nanotrap,” Rosenberg said. “It’s easily modulated. We can switch out different antibodies or proteins or target different immune cells, based on what we need with new variants.”

Storage is simple, as the Nanotraps can be kept in a standard freezer, and administration is simple, using a nasal spray. The researchers said it is also possible to serve as a vaccine by optimisation of the Nanotrap formulation.

Source: Phys.Org

Journal information: Min Chen et al, Nanotraps for the containment and clearance of SARS-CoV-2, Matter (2021). DOI: 10.1016/j.matt.2021.04.005

Categories : Medical Research & TechnologyTags :

Spacesuit Tech Leads to Improved Patient Outcomes

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A tech startup is pioneering wearable health technology derived from spacesuit technology.

Maarten Sierhuis, a NASA alum, commented to Rachna Dhamija, a tech veteran and his future cofounder saying, “If your dad would just wear a space suit, I could monitor him”. Both had ageing parents with health issues.

Having worked for 12 years as a senior research scientist at NASA, Sierhuis used sensors and artificial intelligence (AI) to monitor astronauts in space. When astronauts go on spacewalks, their spacesuits contain various sensors that monitor their vitals, with the data being sent to NASA and distributed to the flight surgeon, biomedical engineers, and others. The ground-based crew uses that information to guide its support efforts—perhaps a reminder to drink some water and avert dehydration, or to take a short break to lower heart rate. This technology—called the Brahms Intelligent Agent platform—was licensed to Ejenta from NASA. Now, hospitals and health systems are using it to help better their patient care.

“When we started the company, we just had a very strong conviction that our parents deserve the same level of care NASA provides its astronauts,” Dhamija said.

Ejenta integrates wearable and home sensors that gather data from patients with AI-driven virtual assistants. Using a chat function, patients can use the platform to exchange messages with these assistants, called “intelligent agents” by Ejenta, right from their homes. Clinicians can securely access patient information from the Ejenta platform to better inform their care decisions.

Advances in cloud computing enabled the technology to be adapted from space to the Earth. Ejenta’s founders use a cloud infrastructure to securely collect, store and analyse health data.

Ejenta—whose name is a Bengali slang term for “agents”— is one of them. The company, which was founded in 2012, originally focused on government-related work, including projects for NASA. However, in the last four years, Ejenta evolved into a digital health company. Dhamija said the company’s AI-driven technology is what makes Ejenta unique from other digital health startups.

“There are a lot of healthcare devices available to consumers, but what’s missing is AI and the automation that can turn this data into insights a doctor can use—actionable data to make care more preventative and more proactive,” she said.

Ejenta uses its NASA technology to take data from wearable Internet of Things (IoT) devices and at-home sensors to monitor a patient’s health. Patients can interact with their assistant via text or voice and ask questions like, “What medication do I need to take with breakfast?”and receive an appropriate answer.

A clinical trial with Ejenta by one of the country’s largest healthcare providers, saw heart failure readmissions dropped by 56%. Readmissions come are costly for both patients and the healthcare system, so this application can save considerable amounts of money as well as improving the patient’s quality of life. Ejenta, in separate clinical trials, also contributed to improved outcomes for women who had high-risk pregnancies, reducing risk for gestational diabetes, preterm birth and cesarean sections. These successes were made possible by years of difficult development.

“We had a big challenge adapting our solution, which was originally designed to monitor 12 astronauts in space, to scale up to support thousands of patients across a number of different customer types and a number of different health conditions while still being HIPAA compliant,” Dhamija said.

However, by leveraging Amazon Webs Servers (AWS) as its cloud provider, Ejenta was able to scale up. Dhamija said her team chose AWS because it offers both flexibility and scalability in a secure cloud environment, which is critical when dealing with healthcare data. Ejenta wanted a “cloud provider that had a reputation for providing HIPAA-compliant services our customers would trust,” she said.

Ejenta was part of the Alexa Accelerator, an Amazon programme to help companies incorporate voice technology into their innovations. Before entering the programme, Ejenta had used Alexa to support improved diabetes care management for patients. It continued this work during the accelerator.

“Alexa is one of the only voice-based solutions that gave us the ability to engage customers, whether it’s patients or their family, with voice and do it in a HIPAA-compliant way,” Dhamija said.

Ejenta’s participation in the accelerator led to its involvement in AWS Connections, a program that introduces startups to large organisations that have specific technological or business needs. Through this programme, Ejenta is developing a health and communication management system for astronauts in deep space to relay health informationa and communicate with their families.

“It’s translational, meaning it can be applied for both Earth and space,” Dhamija said. “If you look at some of the problems we face on Earth or space, they do inform each other, so the goal is to have our Earth-based work inform space, and vice versa.”

Source: Forbes

Categories : Medical Research & TechnologyTags :

Harnessing Tailocins, Antibacterial ‘Homing Missiles’

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A Berkeley Lab-led team is investigating how to harness tailocins, antibacterial nanomachine ‘weapons’ akin to phages but produced by certain bacteria in suicide attacks against other strains.

“Tailocins are extremely strong protein nanomachines made by bacteria,” explained Vivek Mutalik, a research scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) who studies tailocins and phages, the bacteria-infecting viruses that tailocins appear to be remnants of. “They look like phages but they don’t have the capsid, which is the ‘head’ of the phage that contains the viral DNA and replication machinery. So, they’re like a spring-powered needle that goes and sits on the target cell, then appears to poke all the way through the cell membrane making a hole to the cytoplasm, so the cell loses its ions and contents and collapses.”

Many bacteria can produce tailocins, seemingly under stress conditions. However, the tailocins are only lethal to specific strains, and seem to be used by bacteria to compete with rivals. Since they are so similar to phages, scientists believe that tailocins are repurposed from DNA that was injected into bacterial genomes from viral infections.

According to Mutalik, tailocins kill the bacteria that produce them as they erupt through the membrane, much the way replicated viruses do. However, once released, the tailocins selectively target certain strains and not the host lineage cells.

“They benefit kin but the individual is sacrificed, which is a type of altruistic behavior. But we don’t yet understand how this phenomenon happens in nature,” Mutalik commented. Scientists also don’t know precisely how the stabbing needle plunger of the tailocin functions.

These topics, and tailocins as a whole, are an area of hot research due to the many possible applications. Mutalik and his colleagues in Berkeley Lab’s Biosciences Area along with collaborators at UC Berkeley are interested in harnessing tailocins to better study microbiomes. Other groups are keen to use tailocins as an alternative to traditional antibiotics -which indiscriminately wipe out beneficial strains alongside the bad and are increasingly ineffective due to the evolution of drug-resistance traits.
There is also great interest in using tailocins as an alternative to antibiotics, due to increasing antibiotic resistance and the fact that conventional antibiotics wipe out beneficial strains along with the disease-causing ones.

In their most recent paper, the collaborative Berkeley team explored the genetic basis and physical mechanisms governing how tailocins attack specific strains, and looked at genetic similarities and differences between tailocin producers and their target strains.

Upon examination of 12 strains of tailocin-using soil bacteria, the researchers found that differences in the lipopolysaccharides on the outer membranes determined whether they were targeted by a particular tailocin.

“The bacteria we studied live in a challenging, resource-poor environment, so we’re interested to see how they might be using tailocins to fight for survival,” said co-lead author Adam Arkin, a senior faculty scientist in the Biosciences Area and technical co-manager of the Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA) Scientific Focus Area. Arkin observed that although bacteria can easily be induced to produce tailocins in the lab, as well as scale up for mass production for medicinal applications, it is not well understood how bacteria deploy tailocins in their natural environment, and how or why particular strains are so precisely targeted.

“Once we understand the targeting mechanisms, we can start using these tailocins ourselves,” Arkin added. “The potential for medicine is obviously huge, but it would also be incredible for the kind of science we do, which is studying how environmental microbes interact and the roles of these interactions in important ecological processes, like carbon sequestration and nitrogen processing.”

At the moment, it is difficult to observe what is happening in a bacterial community, but tailocins could remove individual strains with precision to allow a better understanding of the situation.

Follow-up studies being conducted involve taking atomic-level images of the taolicins in action.

Source: SciTech Daily

Journal information: “Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins” by Sean Carim, et al., 1 March 2021, The ISME Journal. DOI: 10.1038/s41396-021-00921-1

Categories : Medical Research & TechnologyTags :

New X-Ray Tool to Spy into Virus’ Cellular Subversion

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A new X-Ray tool called the Compact Cell-Imaging Device (CoCID) will seek to answer the questions of how viruses penetrate cells, and disrupt and subvert cellular processes to produce more virus copies.

In order to advance research into viral diseases, the aim of the project is to develop a particularly suitable cell-imaging method – which has so far been of limited access to researchers – for extensive application in medical research.

A particularly high-performance method of cell-imaging is soft X-ray microscopy (SXM), explained Dr Venera Weinhardt from the Centre for Organismal Studies of Heidelberg University. A physicist specialising in innovative X-ray procedures, she is head of the Molecular Virology division at the Department of Infectious Diseases of Heidelberg University Hospital. “SXM makes use of the special properties of the soft X-ray spectrum in order to look into the interior of a single intact cell and generate three-dimensional images of its whole internal structure. That also reveals the changes induced by viral infections,” explained Dr Weinhardt. 
Thus, soft X-ray microscopy is distinct from methods like electron microscopy, which can visualise individual parts of a cell but not the whole interior.

Professor Ralf Bartenschlager, a Molecular Virologist at the Ruprecht-Karls-Universität Heidelberg commented, “As a virologist working on how SARS-CoV-2 interacts with and alters its host cell, we will greatly benefit from the development of a soft X-ray microscope that allows us to gain unprecedented insights into this intimate interaction. We have previously used several imaging technologies to address the question of host cell reprogramming by viruses, but each technique has its limitations.”

Since the illumination required for this type of microscopy comes from huge particle accelerators called synchrotrons, currently SXM can only be performed at five research stations in the entire world. The main feature of CoCID therefore lies in further developing a miniaturised soft X-ray approach which has been patented by SiriusXT, a spin-out company from University College Dublin. The breakthrough technology will reduce the size of the X-ray source from a football-field sized synchrotron, instead using a laser-produced plasma (LPP) device that can fit on a bench.

“The SXM microscope developed by SiriusXT performs just as well but is many times smaller, less expensive, and still very fast.” said Dr Weinhardt.

Heidelberg researchers are particularly interested in the potential of the new technology in researching SARS-CoV-2. Prof Bartenschlager’s working group is mainly concerned with how the virus reprograms its host cells. He said that SXM images created under the leadership of Dr Weinhardt at Lawrence Berkeley National Laboratory in California are already promising in this respect.

Three-dimensional images of cells infected with SARS-CoV-2 were generated thanks to a cooperation agreement with the European Molecular Biology Laboratory (EMBL) in Heidelberg.

“Through working with these images we have a pretty good idea of what factors play a role with imaging in connection with the virus-infected cells and we can pass these findings on to the CoCID consortium. As soon as the soft X-ray prototype from Dublin is up and running we will also deliver samples of infected cells, enable a direct comparison with available images and provide support in interpreting data,” said Prof Bartenschlager.

According to the Heidelberg researchers, a soft X-ray microscopy available for daily use should have distinct advantages over current techniques, such as being much faster. Prof Bartenschlager said: “We can’t afford long waits or a time-intensive method when it comes to novel viruses such as SARS-CoV-2, which we learn something new about and which changes on a daily basis.”

Source: News-Medical.Net

Categories : Genetics Medical Research & TechnologyTags :

New Bioluminescent System Illuminates Biological Processes

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Scientists at the Federal University of São Carlos (UFSCar) have developed a new bioluminescent system that can enable greatly improved imaging of biological and pathological processes in organisms.

Luciferases are enzymes that catalyse the oxidation of luciferins present in organisms such as fireflies, which results in bioluminescence in the visible light spectrum. Images of cell cultures and live animal models are made using the luciferin-luciferase system found in fireflies. For example, this can show the structure and activity of tumours, or follow the viral process in cells, helping physicians develop treatments.

“We obtained a novel luciferin-luciferase system that produces far-red light at the wavelength of 650 nanometres and emits the brightest bioluminescence ever reported in this part of the spectrum,” said principal investigator Professor Vadim Viviani, biochemist at UFSCar. “It’s a highly promising result for bioluminescence imaging of biological and pathological processes in mammalian tissues.”

“Red bioluminescence is preferred when imaging biological or pathological processes in mammalian tissues because haemoglobin, myoglobin and melanin absorb little long-wavelength light. Detection is best of all in the far red and near-infrared bands, but bioluminescent systems that naturally emit far red light don’t exist,” Prof Viviani added.

“Some genetically modified forms of luciferase and synthetic analogs of natural luciferins are produced commercially. In conjunction, they produce light at wavelengths as long as 700 nanometers, but the light produced by these artificial systems is generally much weaker and more short-lived than light from natural bioluminescent systems.”

Prof Viviani and collaborators genetically modified luciferase from the Railroad worm Phrixothrix hirtus, the only luciferase that naturally emits red light, and combined with luciferin analogues synthesised by colleagues at the University of Electro-Communications in Tokyo. The resulting luciferin-luciferase generates a much more efficient far-red bioluminescence.

“Our best combination produces far-red at 650 nanometres, three times brighter than natural luciferin and luciferase, and roughly 1000 times brighter than the same luciferase with a commercial analog,” Viviani said.

“Besides the long-wavelength and intense brightness, our combination has better thermal stability and cell membrane penetrability. Above all, it produces more lasting continuous bioluminescence, taking at least an hour to decay and significantly facilitating the real-time imaging of biological and pathological processes.”

Source: News-Medical.Net

Journal information: Viviani, R. V, et al. (2021) A Very Bright Far-Red Bioluminescence Emitting Combination Based on Engineered Railroad Worm Luciferase and 6′-Amino-Analogs for Bioimaging Purposes. International Journal of Molecular Sciences. doi.org/10.3390/ijms22010303.