NTU Singapore Team Develops Portable Device That Creates 3D Images of Skin in 10 Minutes (Medicine)

A team from Nanyang Technological University, Singapore (NTU Singapore) has developed a portable device that produces high-resolution 3D images of human skin within 10 minutes.

The team said the portable skin mapping (imaging) device could be used to assess the severity of skin conditions, such as eczema and psoriasis.

3D skin mapping could be useful to clinicians, as most equipment used to assess skin conditions only provide 2D images of the skin surface. As the device also maps out the depth of the ridges and grooves of the skin at up to 2mm, it could also help with monitoring wound healing.

The device presses a specially devised film onto the subject’s skin to obtain an imprint of up to 5 by 5 centimetres, which is then subjected to an electric charge, generating a 3D image.

The researchers designed and 3D printed a prototype of their device using polylactic acid (PLA), a biodegradable bioplastic. The battery-operated device which measures 7cm by 10cm weighs only 100 grams.

The made-in-NTU prototype is developed at a fraction of the cost of devices with comparable technologies, such as optical coherence tomography (OCT) machines, which may cost thousands of dollars and weigh up to 30 kilogrammes.

Assistant Professor Grzegorz Lisak from NTU’s School of Civil and Environmental Engineering, who led the research, said: “Our non-invasive, simple and inexpensive device could be used to complement current methods of diagnosing and treating skin diseases. In rural areas that do not have ready access to healthcare, non-medically trained personnel can make skin maps using the device and send them to physicians for assessment.”

Providing an independent comment on how the device may be useful to clinicians, Dr Yew Yik Weng, a Consultant Dermatologist at the National Skin Centre and an Assistant Professor at NTU’s Lee Kong Chian School of Medicine, said: “The technology is an interesting way to map the surface texture of human skin. It could be a useful method to map skin texture and wound healing in a 3D manner, which is especially important in research and clinical trials. As the device is battery-operated and portable, there is a lot of potential in its development into a tool for point of care assessment in clinical settings.”

Asst Prof Dr Yew added: “The device could be especially useful in studies involving wound healing, as we are currently lacking a tool that maps the length and the depth of skin ridges. Currently, we rely on photographs or measurements in our trials which could only provide a 2D assessment.”

First author of the study, Mr Fu Xiaoxu, a PhD student from NTU’s School of Civil and Environmental Engineering, said: “The 3D skin mapping device is simple to operate. On top of that, a 1.5V dry battery is all that is necessary to run the device. It is an example of a basic, yet very effective application of electrochemistry, as no expensive electronic hardware is required.”

Published in the scientific journal Analytica Chimica Acta this month, the technology was developed by Asst Prof Lisak, who is also Director of Residues & Resource Reclamation Centre at the Nanyang Environment and Water Research Institute (NEWRI) and his PhD student, Mr Fu Xiaoxu.

The ‘golden’ solution to 3D skin mapping

The key component of the NTU device is a polymer called PEDOT:PSS, commonly used in solar panels to convert light into electricity. However, the team found a different use for its electrical conductivity – to reproduce skin patterns on gold-coated film. Gold is used as it has excellent electrical conductivity and flexibility.

To use the device, a person pushes a button to press the gold-coated film onto the subject’s skin to obtain an imprint. This causes sebum, an oily substance produced by the skin, to be transferred onto the film, creating an imprint of the skin surface.

Next, the imprint of the skin is transferred to the portable device where a set of electrodes is immersed in a solution. With another push of a button, the device triggers a flow of electric charge, causing PEDOT:PSS to be deposited on the surfaces of the gold-coated film in areas that are not covered with sebum. This results in a high-resolution 3D map of the skin, which reflects the ridges and grooves of the subject’s skin.

Using pig skin as a model, the researchers demonstrated that the technology was able to map the pattern of various wounds such as punctures, lacerations, abrasions, and incisions.

The team also showed that even the complex network of wrinkles on the back of a human hand could be captured on the film. The thin film is also flexible enough to map features on uneven skin areas, such as the creases of an elbow and fingerprints.

Asst Prof Lisak added: “The device has also proven to be effective in lifting fingerprints and gives a high-resolution 3D image of their characteristics.”

Commenting on the potential uses of the device, Asst Prof Dr Yew added: “The device may aid in fingerprint identification, which is commonly performed in forensic analysis. The device could offer a higher degree of accuracy when it comes to differentiating between similar prints, due to the 3D nature of its imagery.”

To further validate its efficacy, the team is exploring conducting clinical trials later this year to test the feasibility of their device, as well as other potential therapeutic uses.

The NTU research paper titled Diagnostics of skin features through 3D skin mapping based on electro-controlled deposition of conducting polymers onto metal-sebum modified surfaces and their possible applications in skin treatment“, is published in Analytica Chimica Acta, 15 January 2021. DOI 10.1016/J.ACA.2020.10.056

Featured image: (Left to Right) Members of the NTU research team include Assistant Professor Grzegorz Lisak from NTU’s School of Civil and Environmental Engineering, PhD student Yi-Heng Cheong, the study’s first author and PhD student Fu Xiaoxu, and Research Associate Ashiq Ahamed. © NTU Singapore

Provided by Nanyang Technological University

About Nanyang Technological University, Singapore

A research-intensive public university, Nanyang Technological University, Singapore (NTU Singapore) has 33,000 undergraduate and postgraduate students in the Engineering, Business, Science, Humanities, Arts, & Social Sciences, and Graduate colleges. It also has a medical school, the Lee Kong Chian School of Medicine, established jointly with Imperial College London.

NTU is also home to world-renowned autonomous institutes – the National Institute of Education, S Rajaratnam School of International Studies, Earth Observatory of Singapore, and Singapore Centre for Environmental Life Sciences Engineering – and various leading research centres such as the Nanyang Environment & Water Research Institute (NEWRI) and Energy Research Institute @ NTU (ERI@N).

Ranked amongst the world’s top universities by QS, NTU has also been named the world’s top young university for the last seven years. The University’s main campus is frequently listed among the Top 15 most beautiful university campuses in the world and it has 57 Green Mark-certified (equivalent to LEED-certified) building projects, of which 95% are certified Green Mark Platinum. Apart from its main campus, NTU also has a campus in Singapore’s healthcare district.

Under the NTU Smart Campus vision, the University harnesses the power of digital technology and tech-enabled solutions to support better learning and living experiences, the discovery of new knowledge, and the sustainability of resources.

For more information, visit www.ntu.edu.sg

Novel Polymer that Toughens Up and Changes Color Upon Mechanical Stress (Material Science)

Scientists at Tokyo Institute of Technology (Tokyo Tech) developed a polymer whose properties change markedly after being exposed to mechanical stress. In bulk form, the mechano-responsive polymer shows color changing, fluorescence, and self-strengthening abilities even under simple compression or extension. These fundamental findings are unprecedented in the field of mechanochemistry and could pave the way for numerous applications in materials science.

A fascinating and crucial ability of biological tissue, such as muscle, is self-healing and self-strengthening in response to damage caused by external forces. Most human-made polymers, on the other hand, break irreversibly under enough mechanical stress, which makes them less useful for certain critical applications like manufacturing artificial organs. But what if we could design polymers that reacted chemically to mechanical stimuli and used this energy to enhance their properties?

This goal, which has proven to be a big challenge, is under the spotlight in the field of mechanochemistry. In a recent study published in Angewandte Chemie International Edition, a team of scientists from Tokyo Tech, Yamagata University, and Sagami Chemical Research Institute, Japan, made remarkable progress with bulk self-strengthening polymers. Professor Hideyuki Otsuka, who led the study, explains their motivation: “Furthering the development of elegant bulk systems in which a force-induced reaction causes a clear change in mechanical properties would represent a game-changing advance in mechanochemistry, polymer chemistry, and materials science.” They achieved this goal by focusing on difluorenylsuccinonitrile (DFSN), a ‘mechanophore’ or molecule that responds to mechanical stress.

The team created segmented polyurethane polymeric chains with hard as well as soft functional segments. The soft segments contain DFSN molecules acting as their “weakest link,” with both of its halves joined by a single covalent bond. The soft segments also have their side chains topped off with methacryloyl units. Upon applying mechanical stress, such as simple compression or extension, on the polymer, the DFSN molecule splits into two equal cyanofluorene (CF) radicals. These CF radicals, unlike DFSN, acquire a pink color, making it easy to visually detect mechanical damage.

Most importantly, the CF radicals react with the methacryloyl units in the side chains of other polymers, causing separate polymers to chemically hook to one another in a process known as cross-linking. This phenomenon ultimately makes the overall strength of the bulk material go up as polymers become more chemically intertwined. This chemical cross-linking effect, as the scientists proved experimentally, becomes more pronounced as more compression cycles are performed on the segmented polymer samples because more DFSN molecules are split into CF radicals.

In addition, the team created a slight variant of their segmented polymer that not only turns pink but also exhibits fluorescence under ultraviolet irradiation when mechanical force is applied to it. This functionality comes in handy when trying to more accurately quantify the extent of the damage done by mechanical stress.

The attractive properties and functionalities of the developed polymers are useful, for example, for intuitive damage detection and the creation of adaptive materials. Expressing excitement for their findings, Otsuka remarks: “We successfully developed unprecedented mechanoresponsive polymers that exhibit color change, fluorescence, and self-strengthening ability, marking the first report of force-induced cross-linking reactions achieved by simply the extension or compression of a bulk film. Our findings represent a significant advance in the fundamental research of mechanochemistry and its applications in material science.”

As more mechano-responsive materials with unique functions are developed, we can expect to explore their myriad applications in various industrial and engineering fields. Be sure to keep an eye out for further progress in mechanochemistry!

Featured image: Segmented polyurethanes (SPUs) that contain di-fluorenyl succinonitrile (DFSN) moieties and methacryloyl groups were synthesized. The obtained elastomers generated pink cyanofluorene radicals and changed color by compression or extension. This is the first example of force-induced cross-linking reactions achieved by only the extension or compression of a bulk film. © Tokyo Tech

Reference: Seshimo, K., Sakai, H., Watabe, T., Aoki, D., Sugita, H., Mikami, K., Mao, Y., Ishigami, A., Nishitsuji, S., Kurose, T., Ito, H. and Otsuka, H. (2021), Segmented Polyurethane Elastomers with Mechanochromic and Self‐strengthening Functions. Angew. Chem. Int. Ed.. Accepted Author Manuscript. https://doi.org/10.1002/anie.202015196

Provided by Tokyo Institute of Technology

Study Challenges Ecology’s ‘Field of Dreams’ Hypothesis (Ecology)

Restoring habitat requires much more than just the right plants

If you build it, they might not come. That’s the key finding of a new study on habitat restoration practices that challenges a commonly accepted principle in ecology.

The study tested the “Field of Dreams” hypothesis, which predicts that restoring plant biodiversity will lead to recovery of animal biodiversity. The prediction, which often guides restoration practices, is infrequently tested because restoration studies typically measure plant or animal biodiversity, but rarely both, said lead author Pete Guiden, a post-doctoral researcher at Northern Illinois University.

Guiden and NIU colleagues studied 17 research plots of restored tallgrass prairie, measuring biodiversity in four animal communities—snakes, small mammals and ground and dung beetles. “We wanted to know if the most diverse animal communities were found in the most diverse plant communities, or if something else is responsible for patterns of animal biodiversity,” he said.

While the scientists did find some positive connections between plant and animal biodiversity, the gains weren’t nearly as strong as benefits derived from implementation of restoration management strategies.

NIU postdoctoral researcher Pete Guiden.

“We found that the effects of management strategies like controlled burns and bison reintroduction on animal communities were six times stronger on average than the effects of plant biodiversity,” Guiden said.

“The most important effects of restoration on animal biodiversity had little to do with plant community biodiversity,” he added. “So management practices focused on restoring plants might be insufficient to also restore animals.”

The study is published in the Proceedings of the National Academy of Sciences.

Co-authors include NIU professors Holly Jones (biologyenvironmental studies) and Richard King (biology); NIU post-doctoral fellow John Vanek; NIU graduate student Erin Rowland; former NIU students Ryan Blackburn, Anna Farrell, Jessica Fliginger, Sheryl C. Hosler, Melissa Nelson and Kirstie Savage; and former NIU professor Nicholas Barber of San Diego State University.

The research was carried out by Professor Holly Jones’ Evidence-based Restoration Laboratory. Jones holds a joint appointment at NIU in biological sciences and environmental studies. Credit: Northern Illinois University

“This is an important study,” said Jones, whose Evidence-based Restoration Laboratory at NIU carried out the research. “With Earth’s biodiversity rapidly disappearing, ecological restoration has emerged as an important strategy to slow or reverse biodiversity losses. Critical tests of the Field of Dreams and other hypotheses are needed to improve restoration science and ensure we get the most bang for our buck.”

The study results were a surprise to the authors, who had predicted that plant biodiversity would have stronger effects on animal biodiversity than management strategies.

“We expected plant biodiversity to be important because having more plant species allows animals to split up food resources or habitat,” Guiden said. “However, the strong effects of land management on animal biodiversity highlight the important role of people in shaping the quantity or quality of habitat, especially through disturbance regimes used in restoration.”

The new study measured biodiversity in four animal communities at Nachusa Grasslands—snakes, small mammals such as this prairie vole and ground and dung beetles. Credit: Holly Jones

The scientists’ work was conducted at Nachusa Grasslands, a 3,800-acre nature preserve in Franklin Grove, Illinois, managed by The Nature Conservancy. Since 1986, Nachusa crew members and volunteers have been reconnecting remnant prairie, woodlands and wetlands through habitat restoration to create one of the largest and most biologically diverse grasslands in Illinois. Tallgrass prairie is one of the most globally imperiled ecosystems.

“While Illinois is known as the Prairie State, 99.9 percent of its prairie has been lost to agriculture and development,” Jones said. “Nachusa Grasslands is an incredible success story. What The Nature Conservancy has done is show us we can restore ecosystems. What was once rows of corn is now a really high-functioning prairie that also serves as a living laboratory for restoration scientists.”

Snakes were among the animal communities monitored in the study on biodiversity. Credit: Richard King

The 17 research sites studied measured 60-by-60 meters and had restoration ages spanning three to 32 years. Each site experienced a unique controlled-burn history, and bison had been reintroduced to eight of the sites between 2014 and 2015. For Nachusa Grasslands, fire and bison-grazing are key management practices that are components of healthy prairies and together can increase plant and animal biodiversity.

By simultaneously measuring plant and animal responses to restoration disturbances, the scientists were able to tease out and compare management-driven and plant-driven effects.

Guiden said each animal community studied differed considerably in its specific responses to restoration. In fact, the study found that restoration can simultaneously have positive and negative effects on biodiversity through different pathways, which may help reconcile why there can be variation in restoration outcomes.

For example, in older restorations, high diversity among plants resulted in a decrease in a specific diversity measure for dung beetles, likely because key resources became more difficult to find. On the other hand, older restorations also had soil conditions that provided high quality habitat for a wide range of other species.

Guiden also noted that the animals studied in this research project are decomposers (dung beetles), omnivores (small mammals) or carnivores (snakes, ground beetles). “Animal communities composed of herbivores, particularly species highly specialized on specific prairie plants, may show stronger relationships to plant diversity,” he said.

A field of Ohio spiderwort rivals the skyscape at Nachusa grasslands. Credit: Pete Guiden

Ecosystems are difficult to restore because they represent such highly intricate webs of species’ interactions with each other and their environments, Jones said.

“Our study shows that it’s critical to define restoration goals before projects get off the ground and to measure progress,” she said. “This will help ensure the restoration is eliciting the desired responses.

“Perhaps more importantly, our study shows these active restoration techniques of introducing megaherbivores like bison, which were near extinction last century, and fire regimes that Indigenous people used to set to prairies, are absolutely critical components to recreating those complex webs of species and interactions. Seeding alone gets us started, but extra management super charges the animal communities that are critical to maintaining healthy prairies.”

Featured image: The new study found that, when restoring habitat, the effects of management strategies on animal communities were six times stronger on average than the effects of plant biodiversity. One such management strategy in prairie restoration is the reintroduction of bison, seen here at Nachusa Grasslands. Credit: Holly Jones

Reference: Peter W. Guiden, Nicholas A. Barber, Ryan Blackburn, Anna Farrell, Jessica Fliginger, Sheryl C. Hosler, Richard B. King, Melissa Nelson, Erin G. Rowland, Kirstie Savage, John P. Vanek, Holly P. Jones, “Effects of management outweigh effects of plant diversity on restored animal communities in tallgrass prairies”, Proceedings of the National Academy of Sciences Feb 2021, 118 (5) e2015421118; DOI: 10.1073/pnas.2015421118

Provided by Northern Illinois University

“Genetic SD-card”: Scientists Obtained New Methods to Improve the Genome Editing System (Medicine)

Researchers take a step in the development of genome editing technology.

Researchers from Peter the Great St.Petersburg Polytechnic University (SPbPU) in collaboration with colleagues from Belgium take a step in the development of genome editing technology. Currently it is possible to deliver genetic material of different sizes and structures to organs and tissues. This is the key to eliminating DNA defects and treating more patients. The project is guided by Professor Gleb Sukhorukov and supported by the Russian Science Foundation. Research results were published in Particle & Particle Systems Characterization journal.

An international research group developed a polymer carrier with a number of unique properties, several types of genetic material can be loaded in its structure. In particular, the scientists managed to load genetic material of various sizes and structures into “universal containers”. From small interfering RNAs (siRNAs) to messenger RNAs (mRNAs). The efficiency of delivery was demonstrated on human stem cells.

“Nowadays most of the vaccines, including those for COVID-19, are made on the basis of mRNA. This is a kind of “genetic SD-card” with information which activates human immune system, thus teaches it how to deal with the “enemy proteins” of the virus. Typically, for medical purposes, different types of carriers are used to deliver specific molecules, we proved that it is possible to deliver genetic materials of different sizes using one type of carrier. This technology opens up new horizons for the development of non-viral delivery systems”, – notes Alexander Timin, head of the Laboratory for microencapsulation and controlled delivery of biologically active compounds at St. Petersburg Polytechnic University.

Scientists added that the micron-scaled carrier with incorporated genetic material can be delivered by systemic administration, or locally (directly into the tumor focus for cancer).

“The study is conducted jointly with the Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, which provided the patients’mesenchymal stem cells (cells building organs and tissues) for the experiments. In the future, we plan to conduct experiments on tumor-bearing laboratory animals in order to find out how the genetic material delivered to the tumor will be managed, “- said Igor Radchenko, director of the “RASA-Polytech” center.

The Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation is interested in the early implementation of these developments in order to fulfill the recommendations and medical protocols that will be introduced into medical practice.

Featured image: Researchers take a step in the development of genome editing technology © Peter the Great St.Petersburg Polytechnic University

Reference: Tarakanchikova, Y. V., Muslimov, A. R., Zyuzin, M. V., Nazarenko, I., Timin, A. S., Sukhorukov, G. B., Lepik, K. V., Layer‐by‐Layer‐Assembled Capsule Size Affects the Efficiency of Packaging and Delivery of Different Genetic Cargo. Part. Part. Syst. Charact. 2020, 2000228. https://doi.org/10.1002/ppsc.202000228

Provided by Peter the Great Saint- Petersburg Polytechnic University

Air-guiding in Solid-core Optical Waveguides: A Solution For On-chip Trace Gas Spectroscopy (Physics)

Optical waveguides suspended in air are capable to beat free-space laser beams in light-analyte interaction even without complex dispersion engineering. This phenomenon has been predicted more than 20 years ago, yet never observed in experiment.

In a new paper published in Light Science & Application, a team of scientists, led by Professor Jana Jágerská from Department of Science and Technology, UiT The Arctic University of Norway, and co-workers have devised a mid-infrared free standing solid core optical waveguide which pushes the light interaction with the surrounding air beyond what has been reported up until now: 107 % interaction strength compared to that of a free-space beam has been demonstrated.

“The guided mode of our thin waveguide resembles a free-space beam: it is strongly de-localized and travels predominantly in air. But, at the same time, it is still bound to the chip and can be guided along a pre-defined e.g. spiral waveguide path.”

This is a significant achievement from the perspective of basic research but also an important step towards practical applications in on-chip gas sensing. Thanks to the high air-confinement of the guided mode, the waveguide not only improves upon the light-analyte interaction, but the guided light also experiences minimal overlap with the solid waveguide core material. This means that the guided mode is only marginally disturbed by material or structural imperfections, which suppresses undesired loss, scattering or reflections. The waveguide hence delivers transmission nearly free from spurious etalon fringes, which are of utmost importance for applications in trace gas spectroscopy.

“The main killer of precision of TDLAS instruments are [spectral] fringes, and integrated nanophotonic components typically produce plenty of them. Our chips are different. The theoretical reflections on the waveguide facets are as low as 0.1 %, and spurious fringes in transmission are therefore suppressed to below the noise level.”

This optical waveguide fits therefore very well into the prospect of a future miniature trace gas sensors. Sensitive and selective integrated sensors based on the reported waveguide chips would not only down scale the dimensions of existing trace gas analysers, but also allow for microlitre sensing volumes and deployment in distributed sensors networks, leading to new applications in environmental monitoring, biology, medicine, as well as industrial process control.

Featured image: An illustration of the waveguide in a flow cell together with an absorption spectrum of 4 % acetylene measured through the waveguide. Laser beam of 2566 nm wavelength is coupled with an objective lens into the waveguide enclosed in a flow cell with controlled atmosphere. The transmitted light is collected using a detector and the recorded absorption signal is fitted with a known reference spectrum to determine the air-confinement factor. A free-space beam spectrum of a beam passed through the same but empty cell is shown as reference. The graph inset highlights that a 7 % stronger absorption signal is obtained with the waveguide than with the free-space beam, signifying stronger light-analyte interaction. © by Marek Vlk, Anurup Datta, Sebastián Alberti, Henock Demessie Yallew, Vinita Mittal, Ganapathy Senthil Murugan, Jana Jágerská

Reference: Vlk, M., Datta, A., Alberti, S. et al. Extraordinary evanescent field confinement waveguide sensor for mid-infrared trace gas spectroscopy. Light Sci Appl 10, 26 (2021). https://www.nature.com/articles/s41377-021-00470-4 https://doi.org/10.1038/s41377-021-00470-4

Provided by CIOMP

Moffitt Researchers Identify Why CAR T Therapy May Fail in Some Lymphoma Patients (Medicine)

Chimeric antigen receptor T-cell therapy, or CAR T, has been a breakthrough in the treatment of blood cancers such as acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Clinical studies have shown overall response rates of more than 80% with an ongoing response of nearly 40% more than two years after therapy. However, the cellular immunotherapy doesn’t work for every patient. Moffitt Cancer Center, one of the leading centers for cellular immunotherapy, is researching why some patients have a better CAR T response than others and what can be done to improve the treatment’s effectiveness. In a new study published in Blood, the official journal of the American Society of Hematology, Moffitt researchers show that immune dysregulation can directly affect the efficacy of CAR T therapy in patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. It is an aggressive cancer affecting B lymphocytes, a type of white blood cell that helps the body fight infection. Axicabtagene ciloleucel was the first CAR T therapy approved for the treatment of this type of cancer. It is indicated for patients with refractory or relapsed disease, meaning they have failed two or more prior courses of therapy. For CAR T-cell therapy, a patient’s immune cells are collected through a process called apheresis. Those immune cells are genetically modified in a lab, adding a chimeric antigen receptor that helps the T cells locate and kill tumor cells once infused back into the patient.

For this observational study, the research team collected blood and tumor samples from 105 patients treated with axicabtagene ciloleucel. The samples, which were taken before and after therapy, were analyzed. Patients were categorized into two groups: durable responders, meaning they remained in remission at a minimum follow-up of six months following CAR T infusion, and nondurable responders who experienced relapsed lymphoma.

“Large B cell lymphoma patients with active disease already experience immune dysregulation, such as elevated cytokines, altered myeloid cell populations and T cell deficits. Our analysis was to determine how these immune characteristics and inflammation affect the ability for CAR T cells to expand and seek out cancer cells following infusion,” said Frederick Locke, M.D., vice chair of the Blood and Marrow Transplant and Cellular Immunotherapy Department and co-leader of the Immuno-Oncology Program at Moffitt.

The results showed that large tumors lead to immune dysregulation in patients due to chronic interferon signaling within the tumor and high cytokine levels in the patient. Overall, CAR T-cell therapy was less likely to be successful in patients with immune dysregulation. This was attributed to impairment of the growth of CAR T cells in these patients, as well as resistance to CAR T-cell therapy by the tumor due to the expression of multiple immune checkpoints.

“These findings could help improve the way we administer CAR T therapy on two fronts. We can use interventions to help improve the quality of patients’ immune cells prior to apheresis, resulting in a better CAR T product. We can also help better prepare patients’ immune systems to receive the CAR T cells to increase response following infusion,” said Michael Jain, M.D., Ph.D., assistant member of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt.

The researchers stress more study is needed to determine what those interventions would be, but there is hope these findings can help modify therapy to reduce relapses that occur following CAR T therapy.

This study was supported by the National Institutes of Health (P30 CA076292, K23 CA201594), Pinellas Partners, the Hoenle family, The Hyer Family Foundation, and the John Morroni Pinellas County First Responders Ball.

Reference: Michael D. Jain, Hua Zhao, Xuefeng Wang, Reginald Atkins, Meghan Menges, Kayla Reid, Kristen Spitler, Rawan Faramand, Christina A Bachmeier, Erin A. Dean, Biwei Cao, Julio C Chavez, Bijal D Shah, Aleksandr Lazaryan, Taiga Nishihori, Mohammad OMAR Hussaini, Ricardo J Gonzalez, John E Mullinax, Paulo Rodriguez, Jose Conejo-Garcia, Claudio Anasetti, Marco L Davila, Frederick L. Locke; Tumor interferon signaling and suppressive myeloid cells associate with CAR T cell failure in large B cell lymphoma. Blood 2021; blood.2020007445. doi: https://doi.org/10.1182/blood.2020007445

Provided by Moffitt Cancer Center

Iron Release May Contribute to Cell Death in Heart Failure (Biology)

A new study shows that the release of stored iron in heart cells may contribute to heart failure, suggesting potential new approaches to treatment.

A process that releases iron in response to stress may contribute to heart failure, and blocking this process could be a way of protecting the heart, suggests a study in mice published today in eLife.

People with heart failure often have an iron deficiency, leading some scientists to suspect that problems with iron processing in the body may play a role in this condition. The study explains one way that iron processing may contribute to heart failure and suggests potential treatment approaches to protect the heart.

“Iron is essential for many processes in the body including oxygen transport, but too much iron can lead to a build-up of unstable oxygen molecules that can kill cells,” says first author Jumpei Ito, who was a Research Associate at the School of Cardiovascular Medicine and Sciences, King’s College London, UK, at the time the study was carried out, and is now a visiting scientist based at Osaka Medical College, Japan. “We already knew that iron metabolism undergoes changes in heart failure, but it was unclear whether these changes are helpful or harmful.”

To learn more about the role of iron metabolism in heart failure, Ito and colleagues studied mice lacking a protein called the nuclear receptor coactivator 4 (NCOA4), which is necessary to release iron stored in cells when the body’s iron levels are low. They found that these mice developed less severe changes associated with heart failure compared to mice with NCOA4. Specifically, the NCOA4-deficient mice did not develop excessive levels of iron or a build-up of unstable oxygen molecules that can lead to cell death in heart failure.

A compound called ferrostatin-1 inhibits the release of stored iron and reduces the accumulation of unstable oxygen molecules. Further experiments by the team showed that treating mice with NCOA4 with ferrostatin-1 can reduce the amount of cell death in heart failure. “Our results suggest that the release of iron can be detrimental to the heart,” Ito says. “It can lead to unstable oxygen levels, death in heart cells and ultimately heart failure.”

More studies are now needed to understand each step in the process that releases iron and to test whether inhibiting this process could be beneficial to people with heart failure.

“Patients with heart failure who are iron deficient are currently treated with iron supplements, which previous studies have shown reduces their symptoms,” adds senior author Kinya Otsu, the British Heart Foundation Professor of Cardiology at King’s College London. “While our work does not contradict those studies, it does suggest that reducing iron-dependent cell death in the heart could be a potential new treatment strategy for patients.”

Reference: Jumpei Ito et al., “Iron derived from autophagy-mediated ferritin degradation induces cardiomyocyte death and heart failure in mice”, eLife, 2021. DOI: 10.7554/eLife.62174

Provided by Elife

Automated Imaging Detects And Tracks Brain Protein Involved in Alzheimer’s Disease (Neuroscience)

The method may lead to earlier diagnoses, when treatments are most effective

Amyloid-beta and tau are the two key abnormal protein deposits that accumulate in the brain during the development of Alzheimer’s disease, and detecting their buildup at an early stage may allow clinicians to intervene before the condition has a chance to take hold. A team led by investigators at Massachusetts General Hospital (MGH) has now developed an automated method that can identify and track the development of harmful tau deposits in a patient’s brain. The research, which is published in Science Translational Medicine, could lead to earlier diagnoses of Alzheimer’s disease.

“While our understanding of Alzheimer’s disease has increased greatly in recent years, many attempts to treat the condition so far have failed, possibly because medical interventions have taken place after the stage at which the brain injury becomes irreversible,” says lead author Justin Sanchez, a data analyst at MGH’s Gordon Center for Medical Imaging.

In an attempt to develop a method for earlier diagnosis, Sanchez and his colleagues, under the leadership of Keith A. Johnson, MD, of the departments of Radiology and Neurology at MGH, evaluated brain images of amyloid-beta and tau obtained by positron emission tomography, or PET, in 443 adults participating in several observational studies of aging and Alzheimer’s disease. Participants spanned a wide range of ages, with varying degrees of amyloid-beta and cognitive impairment — from healthy 20-year-olds to older patients with a clinical diagnosis of Alzheimer’s dementia. The researchers used an automated method to identify the brain region most vulnerable to initial cortical tau buildup in each individual PET scan.

“We hypothesized that applying our method to PET images would enable us to detect the initial accumulation of cortical tau in cognitively normal people, and to track the spread of tau from this original location to other brain regions in association with amyloid-beta deposition and the cognitive impairment of Alzheimer’s disease,” explains Sanchez. He notes that cortical tau, when it spreads from its site of origin to neocortical brain regions under the influence of amyloid-beta, appears to be the “bullet” that injures brains in Alzheimer’s disease.

The technique revealed that tau deposits first emerge in the rhinal cortex region of the brain, independently from amyloid-beta deposits, before spreading to the nearby temporal neocortex. “We observed initial cortical tau accumulation at this site of origin in cognitively normal individuals without evidence of elevated amyloid-beta, as early as 58 years old,” says Sanchez.

Importantly, when the scientists followed 104 participants for two years, they found that people with the highest initial levels of tau at the point of origin exhibited the most spread of tau throughout the brain over time.

The findings suggest that PET measurements of tau focused on precisely individualized specific brain regions may predict an individual’s risk of future tau accumulation and consequent Alzheimer’s disease. Targeting tau when detected at an early stage might prevent the condition or slow its progression.

“Clinical trials evaluating the efficacy of anti-tau therapeutics would benefit from an automated, individualized imaging method to select cognitively normal individuals vulnerable to impending tau spread, thus advancing our efforts to provide effective interventions for patients at risk for Alzheimer’s disease,” says Sanchez.

This work was supported by the National Institutes of Health.

Featured image: By mapping individuals’ unique brain anatomy, Massachusetts General Hospital researchers have identified early tau PET imaging signals to track Alzheimer’s pathology. Left: Tau PET images for a person with normal cognition. Right: top, 3D brain surface rendering with tau PET overlay; bottom, flat map showing brain surface details, with cortical tau origin (rhinal cortex) outlined in white. © Justin Sanchez

Reference: Justin S. Sanchez, J. Alex Becker et al., “The cortical origin and initial spread of medial temporal tauopathy in Alzheimer’s disease assessed with positron emission tomography”, Science Translational Medicine 20 Jan 2021: Vol. 13, Issue 577, eabc0655 DOI: 10.1126/scitranslmed.abc0655

Provided by Massachusetts General Hospital

Venus Flytraps Found to Produce Magnetic Fields (Physics)

Physicists use atomic magnetometers to measure the biomagnetic signals of the carnivorous plant.

The Venus flytrap (Dionaea muscipula) is a carnivorous plant that encloses its prey using modified leaves as a trap. During this process, electrical signals known as action potentials trigger the closure of the leaf lobes. An interdisciplinary team of scientists has now shown that these electrical signals generate measurable magnetic fields. Using atomic magnetometers, it proved possible to record this biomagnetism. “You could say the investigation is a little like performing an MRI scan in humans,” said physicist Anne Fabricant. “The problem is that the magnetic signals in plants are very weak, which explains why it was extremely difficult to measure them with the help of older technologies.”

Electrical activity in the Venus flytrap is associated with magnetic signals

We know that in the human brain voltage changes in certain regions result from concerted electrical activity that travels through nerve cells in the form of action potentials. Techniques such as electroencephalography (EEG), magnetoencephalography (MEG), and magnetic resonance imaging (MRI) can be used to record these activities and noninvasively diagnose disorders. When plants are stimulated, they also generate electrical signals, which can travel through a cellular network analogous to the human and animal nervous system.

An interdisciplinary team of researchers from Johannes Gutenberg University Mainz (JGU), the Helmholtz Institute Mainz (HIM), the Biocenter of Julius-Maximilians-Universität of Würzburg (JMU), and the Physikalisch-Technisch Bundesanstalt (PTB) in Berlin, Germany’s national meteorology institute, has now demonstrated that electrical activity in the Venus flytrap is also associated with magnetic signals. “We have been able to demonstrate that action potentials in a multicellular plant system produce measurable magnetic fields, something that had never been confirmed before,” said Anne Fabricant, a doctoral candidate in Professor Dmitry Budker’s research group at JGU and HIM.

The trap of Dionaea muscipula consists of bilobed trapping leaves with sensitive hairs, which, when touched, trigger an action potential that travels through the whole trap. After two successive stimuli, the trap closes and any potential insect prey is locked inside and subsequently digested. Interestingly, the trap is electrically excitable in a variety of ways: in addition to mechanical influences such as touch or injury, osmotic energy, for example salt-water loads, and thermal energy in the form of heat or cold can also trigger action potentials. For their study, the research team used heat stimulation to induce action potentials, thereby eliminating potentially disturbing factors such as mechanical background noise in their magnetic measurements.

Biomagnetism – detection of magnetic signals from living organisms

While biomagnetism has been relatively well-researched in humans and animals, so far very little equivalent research has been done in the plant kingdom, using only superconducting-quantum-interference-device (SQUID) magnetometers, bulky instruments which must be cooled to cryogenic temperatures. For the current experiment, the research team used atomic magnetometers to measure the magnetic signals of the Venus flytrap. The sensor is a glass cell filled with a vapor of alkali atoms, which react to small changes in the local magnetic-field environment. These optically pumped magnetometers are more attractive for biological applications because they do not require cryogenic cooling and can also be miniaturized.

The researchers detected magnetic signals with an amplitude of up to 0.5 picotesla from the Venus flytrap, which is millions of times weaker than the Earth’s magnetic field. “The signal magnitude recorded is similar to what is observed during surface measurements of nerve impulses in animals,” explained Anne Fabricant. The JGU physicists aim to measure even smaller signals from other plant species. In the future, such noninvasive technologies could potentially be used in agriculture for crop-plant diagnostics, by detecting electromagnetic responses to sudden temperature changes, pests, or chemical influences without having to damage the plants using electrodes.

The results of the study have been published in Scientific Reports. The project received financial support from the German Research Foundation (DFG), the Carl Zeiss Foundation, and the German Federal Ministry of Education and Research (BMBF).

Featured image: Measuring magnetic signals generated by a Venus flytrap © Anne Fabricant

Reference: A. Fabricant et al., Action potentials induce biomagnetic fields in carnivorous Venus flytrap plants, Scientific Reports 11, 14 January 2021,

Provided by JGU