Scientists Replicated Self-Cleaning Anti-Reflective Coating Of Insects’ Eyes (Biology)

Scientists from Russia and Switzerland have probed into nanostructures covering the corneas of the eyes of small fruit flies. Investigating them the team learned how to produce the safe biodegradable nanocoating with antimicrobial, anti-reflective, and self-cleaning properties in a cost-effective and eco-friendly way. The protection coating might find applications in diverse areas of economics including medicine, nanoelectronics, automotive industry, and textile industry. The article describing these discoveries appears in Nature.

Step-wise increases in magnification are shown, from a macroscale image of a Drosophila head to an atomic force microscopy (AFM) image of a single nipple-type nanostructure coating an ommatidial lens. ©Mikhail Kryuchkov, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.

Scientists from Far Eastern Federal University (FEFU, Russia) teamed up with colleagues from University of Geneva, The University of Lausanne, and Swiss Federal Institute of Technology in Zurich for an interdisciplinary research project during which they were able to artificially reproduce the nanocoating of the corneas of fruit flies (Drosophila flies) naturally designed to protect the eyes of the insects from the smallest dust particles and shut off the reflection of light.

The craft of nanocoating meets demands in various fields of economics. It can wrap up any flat or three-dimensional structure, and, depending on the task, give it anti-reflective, antibacterial, and hydrophobic properties, including self-cleaning. The latter, for example, is a very important feature for expensive reusable overnight ortho-k lenses that correct the eyesight. Similar anti-reflective coatings are already known though created by more complex and costly methods. They are being used on the panels of computers, glasses, paintings in museums can be covered with them in order to exclude reflection and refraction of light.

“We are able to produce the nanocoating in any required quantity given that its design is more cost-effective compared to the modern methods of manufacturing similar structures. The work with natural components requires no special equipment nor significant energy consumption and constraints of chemical etching, lithography, and laser printing,” Vladimir Katanaev explains, the head of the research and Head of the Laboratory of Pharmacology of Natural Compounds in the School of Biomedicine of FEFU. “The development has broad applications. For example, it could be the structural dying of textiles that would change the color depending on the angle of view. It is possible to create a disguise coat based on metamaterials, an antibacterial layer for medical implants, and a self-cleaning coating for contact lenses and windshields. We also believe that if we reinforce the nanocoating, it might be utilized as a basis of flexible miniature transistors prototypes designed for modern electronics.”

Scientists managed to rebuild the corneal coating of small fruit flies via direct and reverse bioengineering methods. First, they took the protective layer apart into its constituent components, which turned out to be retinin (protein) and corneal wax (lipids) and then reassemble it under room temperature conditions, covering glass and plastic surfaces.

According to Vladimir Katanaev, any other types of materials can be nanocoated too. Combinations with different types of wax and genetic manipulations of the retinin protein allow the design of highly diverse and complex functional nanocoatings.

The scientist explains that the mechanism underlying the formation of the protective nanostructures on the corneas of Drosophila flies is a self-organizing process, described by Alan Turing back in 1952 as a reaction-diffusion mechanism. That is consistent with the mathematical modelling performed during the research. This mechanism is also responsible for the patterns forming, for example, on the fur of a zebra or a leopard. The nanostructures that protect the corneas of Drosophila eyes are the first established example of Turing patterns at the nanoscale.

In the course of the research project, scientists made a detailed characterization of the properties of retinin, as this protein has been little studied so far. It turned out that this initially unstructured protein forms a globular structure when interacting with corneal waxes. Thus, scientists took a look deep into the biophysical nature of the self-organization abiding to the Turing model, highlighting an important molecular process likely at the core of the self-organization – the initiation of the protein structuring.

At next stages, the research team aims at developing a model of three-dimensional nanostructuring (with nano-funnels, nanocolumns, nanorolls within the layer of the coating), also based on the Turing mechanism. This work would lie at the very frontier of modern scientific knowledge and can have promising fundamental and technological consequences.

Professor Vladimir Katanaev started studying the structure of the eye of Drosophila fly about 10 years ago. According to the scientist, the first data were obtained almost impromptu by means of atomic force microscopy. During collaboration with the laboratory of Prof. Igor Serdyuk from the Institute of Protein Research (Russian Academy of Sciences), it was discovered that the surface of the corneas of the flies was not smooth but was covered with beautiful patterns of pseudo-ordered nanoscale outgrowths. As it turned out, nanocoatings of this kind were described back in the late 1960s on the surface of the eyes of moths, larger insects to whom these structures also provide an anti-reflex function, reducing the reflection of incident light to zero and allowing to optimize light perception in the darkness.

References: Kryuchkov, M., Bilousov, O., Lehmann, J. et al. Reverse and forward engineering of Drosophila corneal nanocoatings. Nature 585, 383–389 (2020). https://doi.org/10.1038/s41586-020-2707-9

Provided by Far Eastern Federal University

New Insight On Mole Growth Could Aid Development Of Skin Cancer Treatments (Biology)

Moles stop growing when they reach a certain size due to normal interactions between cells, despite having cancer-associated gene mutations, says a new study published today in eLife.

This image shows the progression of pigmented moles in the paw of a mouse. ©Rolando Ruiz-Vega and Emaad Razzak (CC BY 4.0)

The findings in mice could help scientists develop new ways to prevent skin cancer growth that take advantage of the normal mechanisms that control cell growth in the body.

Mutations that activate the protein made by the BRAF gene are believed to contribute to the development of skin cancer. However, recent studies have shown that these mutations do not often cause skin cancer, but instead result in the formation of completely harmless pigmented moles on the skin. In fact, 90% of moles have these cancer-linked mutations but never go on to form tumours. “Exploring why moles stop growing might lead us to a better understanding of what goes wrong in skin cancer,” says lead author Roland Ruiz-Vega, a postdoctoral researcher at the University of California, Irvine, US.

Scientists believe that stress caused by rapid cell growth may stop the growth of moles through a process called oncogene-induced senescence (OIS), but this has not been proven. To test the idea, Ruiz-Vega and colleagues studied mice with BRAF mutations that develop numerous moles.

The team first focused on assessing ‘senescence’, a set of changes in cells usually associated with aging. Using a technique called single-cell RNA sequencing to compare mole cells with normal skin cells, they found that moles are growth-arrested, but no more senescent than normal skin cells. The cells also did not have any apparent differences in gene expression (where a gene is activated to create a necessary protein) that would support the idea of OIS controlling their growth.

Additionally, computer modelling of mole growth did not support the idea of OIS. In fact, the models suggested that mole cells communicate with each other when moles reach a certain size and stop growing. The same kind of communication also takes place in many normal tissues to enable them to achieve and maintain a correct size.

“Our results suggest that moles stop growing as a result of normal cell-to-cell communication, not as a response to stress from cancer genes, potentially changing the way we think about skin cancer,” explains senior author Arthur Lander, Director of the Center for Complex Biological Systems, and Donald Bren Professor of Developmental and Cell Biology, at the University of California, Irvine. “This work paves the way for further research into the mechanisms that control skin cell growth, with the aim of better understanding what goes wrong to cause skin cancer and ultimately developing new treatments to help prevent the disease.”

References: Ronaldo Ruiz Vega et al., “Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes”, Cancer Biology Computational and Systems Biology, 2020. DOI: 10.7554/eLife.61026 link: https://elifesciences.org/articles/61026

Provided by Elife

UCF Researchers Are Working On Tech So Machines Can Thermally ‘Breathe’ (Engineering)

The UCF researchers are developing a way for large machines to “breathe” in and out cooling blasts of water to keep their systems from overheating.

In the era of electric cars, machine learning and ultra-efficient vehicles for space travel, computers and hardware are operating faster and more efficiently. But this increase in power comes with a trade-off: They get superhot.

UCF mechanical and aerospace engineering researchers Khan Rabbi and Shawn Putnam are developing new ways to cool machines and electronics. Rabbi is a doctoral candidate in the department, and Putnam is an associate professor. ©Karen Norum, University of Central Florida Office of Research

To counter this, University of Central Florida researchers are developing a way for large machines to “breathe” in and out cooling blasts of water to keep their systems from overheating.

The findings are detailed in a recent study in the journal Physical Review Fluids.

The process is much like how humans and some animals breath in air to cool their bodies down, except in this case, the machines would be breathing in cool blasts of water, says Khan Rabbi, a doctoral candidate in UCF’s Department of Mechanical and Aerospace Engineering and lead author of the study.

“Our technique used a pulsed water-jet to cool a hot titanium surface,” Rabbi says. “The more water we pumped out of the spray jet nozzles, the greater the amount of heat that transferred between the solid titanium surface and the water droplets, thus cooling the titanium. Fundamentally, an idea of optimum jet-pulsation needs to be generated to ensure maximum heat transfer performance.”

“It is essentially like exhaling the heat from the surface,” he says.

The water is emitted from small water-jet nozzles, about 10 times the thickness of a human hair, that douse a hot surface of a large electronic system and the water is collected in a storage chamber, where it can be pumped out and circulated again to repeat the cooling process. The storage chamber in their study held about 10 ounces of water.

Using high-speed, infrared thermal imaging, the researchers were able to find the optimum amount of water for maximum cooling performance.

Rabbi says everyday applications for the system could include cooling large electronics, space vehicles, batteries in electric vehicles and gas turbines.

Shawn Putnam, an associate professor in UCF’s Department of Mechanical and Aerospace Engineering and study co-author, says that this research is part of an effort to explore different techniques to efficiently cool hot devices and surfaces.

“Most likely, the most versatile and efficient cooling technology will take advantage of several different cooling mechanisms, where pulsed jet cooling is expected to be one of these key contributors,” Putnam says.

The researcher says there are multiple ways to cool hot hardware, but water-jet cooling is a preferred method because it can be adjusted to different directions, has good heat-transfer ability, and uses minimum amounts of water or liquid coolant.

However, it has its drawbacks, namely either over or underwatering that results in floods or dry hotspots. The UCF method overcomes this problem by offering a system that is tunable to hardware needs so that the only water applied is the amount needed and in the right spot.

The technology is needed since once device temperatures surpass a threshold value, for example, 194 degrees Fahrenheit, the device’s performance decreases, Rabbi says.

“For this reason, we need better cooling technologies in place to keep the device temperature well within the maximum temperature for optimum operation,” he says. “We believe this study will provide engineers, scientists and researchers a unique understanding to develop future generation liquid cooling systems.”

References: Khan Md. Rabbi, Jake Carter, and Shawn A. Putnam, “Understanding pulsed jet impingement cooling by instantaneous heat flux matching at solid-liquid interfaces”, Phys. Rev. Fluids 5(9), 094003 – Published 11 September 2020. Link: https://journals.aps.org/prfluids/abstract/10.1103/PhysRevFluids.5.094003

Provided by University Of Central Florida

Anticancer Compounds For B Cell Cancer Therapy Targeting Cellular Stress Response (Medicine)

IRE-1 inhibitors block a main pathway in the endoplasmic reticulum stress response that supports cell survival under stressful conditions and is important for B cell cancer development.

Researchers at The Wistar Institute and collaborators from the University of Notre Dame are developing anticancer compounds targeting a pathway of the endoplasmic reticulum (ER) stress response implicated in the development of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and lymphoma. The study was published online today in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research.

Wistar and collaborators from the University of Notre Dame are developing anticancer compounds targeting a pathway of the endoplasmic reticulum (ER) stress response implicated in the development of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and lymphoma. ©The Wistar Institute

The ER is an important organelle in our cells that oversees the quality control of protein folding under normal conditions and responds to the accumulation of misfolded proteins found under stressful conditions by activating specific mechanisms and signaling pathways such as the IRE-1/XBP-1 pathway that triggers a cascade of events that brings cells back to normal physiological conditions.

The laboratory of Chih-Chi Andrew Hu, Ph.D., professor in the Immunology, Microenvironment & Metastasis Program at Wistar, and collaborators show that targeting the ER stress signaling response is an effective strategy against various B cell cancers that rely upon ER stress signaling response to survive under stressful conditions.

The Wistar Institute and Notre Dame teams are working together to advance a new class of compounds to inhibit IRE-1 protein and block the function of the IRE-1/XBP-1 pathway, which promotes survival of malignant B cells such as MM and CLL cells. The IRE-1 inhibitors being developed by Hu and collaborators have shown promising activity in several preclinical cancer models, compared to other commercially available IRE-1 inhibitors having variable and inconsistent ability to selectively target ER stress signaling in vitro and in vivo.

“We carefully compared many published inhibitors of the IRE-1/XBP-1 pathway with our own inhibitors, showing that our compounds are the most reliable small molecule inhibitors for targeting this pathway in malignant B cells and that many of the other published inhibitors we tested have subpar activity or adverse off-target effects,” said Hu.

The team measured the ability of various inhibitors to block the RNase activity of IRE-1 in test tubes and within the cells. The best-performing molecules were further evaluated for their cytotoxicity against MM, CLL and mantle cell lymphoma, both as single agents and in combination with PI3K/AKT pathway inhibitors that are used as targeted therapy for these malignancies.

Two inhibitors developed by the team, B-I09 and D-F07, showed the highest and longest-lasting inhibitory activity at lower concentrations.

To improve the tumor specificity of these compounds, Hu and colleagues exploited a feature of tumor cells. Since tumor cells typically produce higher hydrogen peroxide (H2O2) levels than normal cells, researchers designed, synthesized and tested novel inhibitors modified with boronate cages, which require high levels of H2O2 to subsequently turn on their inhibitory activity towards IRE-1.

E-F02, a modified prodrug form of B-I09, could be optimally activated by H2O2 to inhibit IRE-1 in malignant B cells. Furthermore, its killing activity was further enhanced in combination with a compound that induces the production of H2O2 in the cells. “E-F02’s inhibitory activity can be controlled spatiotemporally with specificity against cancer cells in vitro,” said co-corresponding author Chih-Hang Anthony Tang, M.D., Ph.D., a staff scientist in the Hu lab. “Next step is to further test it in vivo in our cancer mouse models.”

“We are interested in collaborating with a biotech partner to complete preclinical testing of our lead candidates in order to pursue clinical development of our IRE-1/XBP-1s inhibitors to target human CLL and many other cancers including solid tumors to one day deliver a new highly specific and effective cancer therapy.”

References: Andong Shao, Qin Xu, Walker T. Spalek, Christopher F. Cain, Chang Won Kang, Chih-Hang Anthony Tang, Juan R. Del Valle, and Chih-Chi Andrew Hu, “Development of tumor-targeting IRE-1 inhibitors for B cell cancer therapy”, Molecular Cancer Therapeutics, 2020. DOI: 10.1158/1535-7163.MCT-20-0127

Provided by Wistar Institute

Scientists Use Holographic Imaging To Detect Viruses And Antibodies (Medicine)

A team of New York University scientists has developed a method using holographic imaging to detect both viruses and antibodies. The breakthrough has the potential to aid in medical diagnoses and, specifically, those related to the COVID-19 pandemic.

A rendering of 2019-ncov coronavirus. Photo credit: Maksim Tkachenko/Getty Images/NYU.

“Our approach is based on physical principles that have not previously been used for diagnostic testing,” explains David Grier, a professor of physics at NYU and one of the researchers on the project, which is reported in the journal Soft Matter. “We can detect antibodies and viruses by literally watching them stick to specially prepared test beads.”

If fully realized, this proposed test could be done in under 30 minutes, is highly accurate, and can be performed by minimally trained personnel. Moreover, the method can test for either the virus (current infection) or antibodies (immunity).

The scientists, who also include NYU doctoral candidates Kaitlynn Snyder and Rushna Quddus as well as NYU Chemistry Professor Kent Kirshenbaum and NYU Physics Professor Andy Hollingsworth, base their test on holographic video microscopy, which uses laser beams to record holograms of their test beads. The surfaces of the beads are activated with biochemical binding sites that attract either antibodies or virus particles, depending on the intended test. Binding antibodies or viruses causes the beads to grow by a few billionths of a meter, which the NYU researchers have shown they can detect through changes in the beads’ holograms.

“We can analyze a dozen beads per second,” explains Grier, “which means that we can cut the time for a reliable thousand-bead diagnostic test to 20 minutes. And we can measure those changes rapidly, reliably, and inexpensively.”

The holographic video microscopy is performed by an instrument, xSight, created by Spheryx, a New York-based company Grier co-founded.

The scientists also note the versatility of their method.

“This instrument can count virus particles dispersed in patients’ saliva and also detect and differentiate antibodies dissolved in their blood,” adds Grier. “This flexibility is achieved by changing the composition of the test beads to model what we are testing.

“Each type of bead tests for the presence of a particular target, but can also test for several targets simultaneously. Our holographic analysis distinguishes the different test beads by their size and by their refractive index–an easily controlled optical property.”

The scientists say that this capability can be used to develop libraries of test beads that may be combined into test kits for mixing with patient samples. This will support doctors in distinguishing among possible diagnoses, speeding patients’ treatment, reducing the risk of misdiagnosis, and cutting the cost of healthcare.

References: Kaitlynn Snyder, Rushna Quddus, Andrew D Hollingsworth, Kent Kirshenbaum and David G Grier, “Holographic Immunoassays: Direct Detection of Antibodies Binding to Colloidal Spheres”, Royal Society Of Chemistry, 2020. https://pubs.rsc.org/en/Content/ArticleLanding/2020/SM/D0SM01351J#!divAbstract

Provided by New York University

Researchers Developed Cameras That Can Learn (Science And Technology)

Intelligent cameras could be one step closer thanks to a research collaboration between the Universities of Bristol and Manchester who have developed cameras that can learn and understand what they are seeing.

A Convolutional Neural Network (CNN) on the SCAMP-5D vision system classifying hand gestures at 8,200 frames per second. ©University of Bristol, 2020

Roboticists and artificial intelligence (AI) researchers know there is a problem in how current systems sense and process the world. Currently they are still combining sensors, like digital cameras that are designed for recording images, with computing devices like graphics processing units (GPUs) designed to accelerate graphics for video games.

This means AI systems perceive the world only after recording and transmitting visual information between sensors and processors. But many things that can be seen are often irrelevant for the task at hand, such as the detail of leaves on roadside trees as an autonomous car passes by. However, at the moment all this information is captured by sensors in meticulous detail and sent clogging the system with irrelevant data, consuming power and taking processing time. A different approach is necessary to enable efficient vision for intelligent machines.

Two papers from the Bristol and Manchester collaboration have shown how sensing and learning can be combined to create novel cameras for AI systems.

SCAMP-5d vision system. ©The University of Manchester, 2020

Walterio Mayol-Cuevas, Professor in Robotics, Computer Vision and Mobile Systems at the University of Bristol and principal investigator (PI), commented: “To create efficient perceptual systems we need to push the boundaries beyond the ways we have been following so far.

“We can borrow inspiration from the way natural systems process the visual world – we do not perceive everything – our eyes and our brains work together to make sense of the world and in some cases, the eyes themselves do processing to help the brain reduce what is not relevant.”

This is demonstrated by the way the frog’s eye has detectors that spot fly-like objects, directly at the point where the images are sensed.

SCAMP-5d’s hardware architecture. It incorporates a 256 x 256 PPA array of pixel-processors, each containing light sensor, local memory registers and other functional components. ©The University of Manchester, 2020

The papers, one led by Dr Laurie Bose and the other by Yanan Liu at Bristol, have revealed two refinements towards this goal. By implementing Convolutional Neural Networks (CNNs), a form of AI algorithm for enabling visual understanding, directly on the image plane. The CNNs the team has developed can classify frames at thousands of times per second, without ever having to record these images or send them down the processing pipeline. The researchers considered demonstrations of classifying handwritten numbers, hand gestures and even classifying plankton.

The research suggests a future with intelligent dedicated AI cameras – visual systems that can simply send high-level information to the rest of the system, such as the type of object or event taking place in front of the camera. This approach would make systems far more efficient and secure as no images need be recorded.

The work has been made possible thanks to the SCAMP architecture developed by Piotr Dudek, Professor of Circuits and Systems and PI from the University of Manchester, and his team. The SCAMP is a camera-processor chip that the team describes as a Pixel Processor Array (PPA). A PPA has a processor embedded in each and every pixel which can communicate to each other to process in truly parallel form. This is ideal for CNNs and vision algorithms.

Professor Dudek said: “Integration of sensing, processing and memory at the pixel level is not only enabling high-performance, low-latency systems, but also promises low-power, highly efficient hardware.

“SCAMP devices can be implemented with footprints similar to current camera sensors, but with the ability to have a general-purpose massively parallel processor right at the point of image capture.”

Dr Tom Richardson, Senior Lecturer in Flight Mechanics, at the University of Bristol and a member of the project has been integrating the SCAMP architecture with lightweight drones.

He explained: ‘What is so exciting about these cameras is not only the newly emerging machine learning capability, but the speed at which they run and the lightweight configuration.

“They are absolutely ideal for high speed, highly agile aerial platforms that can literally learn on the fly!’

The research, funded by the Engineering and Physical Sciences Research Council (EPSRC), has shown that it is important to question the assumptions that are out there when AI systems are designed. And things that are often taken for granted, such as cameras, can and should be improved towards the goal of more efficient intelligent machines.

Provided by University Of Bristol

New Method Uses Noise To Make Spectrometers More Accurate (Engineering)

Optical spectrometers are instruments with a wide variety of uses. By measuring the intensity of light across different wavelengths, they can be used to image tissues or measure the chemical composition of everything from a distant galaxy to a leaf. Now researchers at the UC Davis Department of Biomedical Engineering have come up a with a new, rapid method for characterizing and calibrating spectrometers, based on how they respond to “noise.”

Optical spectroscopy splits light and measures the intensity of different wavelengths. It is a powerful technique across a wide range of applications. UC Davis engineers Aaron Kho and Vivek Srinivasan have now found a new way to characterize and cross-calibrate spectroscopy instruments using excess “noise” in a light signal. (Getty Images)

Rendering of prism and spectrum

Optical spectroscopy splits light and measures the intensity of different wavelengths. It is a powerful technique across a wide range of applications. UC Davis engineers Aaron Kho and Vivek Srinivasan have now found a new way to characterize and cross-calibrate spectroscopy instruments using excess “noise” in a light signal. (Getty Images)

Spectral resolution measures how well a spectrometer can distinguish light of different wavelengths. It’s also important to be able to calibrate the spectrometer so that different instruments will give reliably consistent results. Current methods for characterizing and calibrating spectrometers are relatively slow and cumbersome. For example, to measure how the spectrometer responds to different wavelengths, you would shine multiple lasers of different wavelengths on it.

Noise is usually seen as being a nuisance that confuses measurements. But graduate student Aaron Kho, working with Vivek Srinivasan, associate professor in biomedical engineering and ophthalmology, realized that the excess noise in broadband, multiwavelength light could also serve a useful purpose and replace all those individual lasers.

“The spectrometer’s response to noise can be used to infer the spectrometer’s response to a real signal,” Srinivasan said. That’s because the excess noise gives each channel of the spectrum a unique signature.

Faster, more accurate calibration

Instead of using many single-wavelength lasers to measure the spectrometer’s response at each wavelength, the new approach uses only the noise fluctuations that are naturally present in a light source with many wavelengths. In this way, it’s possible to assess the spectrometer’s performance in just a few seconds. The team also showed that they could use a similar approach to cross-calibrate two different spectrometers.

Kho and Srinivasan used the excess noise method in Optical Coherence Tomography (OCT), a technique for imaging living eye tissue. By increasing the resolution of OCT, they were able to discover a new layer in the mouse retina.

The excess noise technique has similarities to laser speckle, Kho said. Speckle – granular patterns formed when lasers are reflected off surfaces – was originally seen as a nuisance but turns out to be useful in imaging, by providing additional information such as blood flow.

“Similarly, we found that excess noise can be useful too,” he said.

These new approaches for characterization and cross-calibration will improve the rigor and reproducibility of data in the many fields that use spectrometers, Srinivasan said, and the insight that excess noise can be useful could lead to the discovery of other applications.

References: Kho, A.M., Zhang, T., Zhu, J. et al. Incoherent excess noise spectrally encodes broadband light sources. Light Sci Appl 9, 172 (2020). https://doi.org/10.1038/s41377-020-00404-6

Provided by University Of California -Davis

Building ‘ToxAll’ — A Smart, Self-Assembling Nano-Vaccine To Prevent Toxoplasmosis (Biology)

Fighting clever parasites requires smart vaccines that can trigger critical immune responses. A University of Chicago-based research team has found a novel way to do that. These experts, specialists in toxoplasmosis and leaders in vaccine design, have focused on one of the most frequent parasitic infections of humans.

Toxoplasmosis

The parasite, Toxoplasma gondii, can cause lifelong infection. It lives in the brain (and sometimes the eyes) of about 30 percent of all humans. When someone drinks contaminated water, eats infected undercooked meat or is exposed to these parasites in soil, it can result in lasting damage. Infection from unrecognized exposure to this microscopic parasite can harm the eyes, damage the brain and, in some cases, lead to death. Toxoplasmosis, according to the CDC, is the second most frequent cause of foodborne-associated death in the United States.

These parasites tend to attack unborn babies, newborns, children and adults. While most healthy adults who are exposed to the parasite never experience any serious symptoms, dormant, unrecognized, smoldering infections can emerge years later in immune-compromised patients. There is currently no vaccine to protect people from this infection.

“We urgently need a vaccine, as well as new and better medicines, to prevent and treat this infection,” said the study’s senior author, Rima McLeod, MD, Professor of Ophthalmology and Visual Science and Pediatrics at University of Chicago and a leading authority on toxoplasmosis.

“Millions of people suffer from these infections,” McLeod said. These neglected infections are often detected too late to prevent irreversible damage, and some patients die if the infection is untreated. Until now, no vaccine has been available for humans and no known medicine in clinical use has been able to eliminate the chronic, encysted form of Toxoplasma.

In an article published in the journal Scientific Reports (Nature), the research team unveiled a clever “immunosense” approach – the use of Self-Assembling Protein Nanoparticles (SAPNs). These have been engineered to boost each component of the immune system. The goal is to protect humans from this common, harmful and sometimes lethal parasite. “Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A11:01, HLA-A02:01 and HLA-B*07:02 transgenic mice” was published online on October 12, 2020.

The team used cell-based and murine models. These mouse models have human immune-response genes to mimic how people can fight the infection. The SAPN scaffold serves as a stimulus, boosting the innate immune response and delivering components of the vaccine to relevant target cells.

“Especially important,” McLeod said, “these novel SAPNs have been engineered to have the size, shape and ability to produce immune responses against Toxoplasma gondii. This triggers a protective effect.”

The team’s approach has been quickly adopted by other investigators. There is ongoing work to immunize against herpetic eye disease, SARS-CoV-2 (COVID19), HIV, malaria and influenza viruses.

The researchers found that their SAPN scaffold can fold reliably into a stable shape. As the immune system perceives it as a foreign invader stimulating a protective immune response, the scaffold can incorporate components that stimulate an immune response against the genetic variants of the parasite.

This can be tailored for people of differing genetic backgrounds. The vaccine becomes a multisystem targeting weapon. The researchers named their new weapon “ToxAll.” They describe it as a “multi-epitope, multi-functional, toxoplasmosis nano-vaccine.”

It contains crucial immunity-stimulating components, mixed with an adjuvant, known as GLA-SE, that appears to be powerful and safe in humans. This type of vaccine, with components from plasmodia, has already been tested in primates for malaria, and is moving into the clinic.

Prior infections with T.gondii before pregnancy can protect a pregnant woman from passing the infection to her unborn child. But when a mother first acquires the infection during pregnancy – before her body can mount an immune response – the parasite can cause significant harm to the unborn child.

The investigators first created a live, attenuated vaccine that can protect mice against toxoplasmosis. Prior natural infection of humans can confer protection, and live vaccines could protect mice. These live vaccines, however, can have safety concerns.

ToxAll was created as a synthetic vaccine that could stimulate danger signals, alerting the immune system to focus on foreign invaders. A crucial part of the process is to create a design with the right properties, assembling particles into predictable shapes that resemble viruses, then enabling the fragments of components of the parasite to educate the “adaptive memory” of the immune system. This creates a long-lasting immune response, including antibodies and protective T lymphocytes.

Protection with the full SAPN, at this point, is not yet available, “but is under development with promising results,” McLeod said. The team is working to expand the use of additional fragments of the parasite. They hope to create a next generation vaccine that could provide lasting immunity against toxoplasmosis – one that could offer a novel, safe, synthetic vaccine to prevent this disease.

The next step is to develop vaccines as part of a “toolbox” that also includes new medicines and novel use of older medicines for prevention and treatment of toxoplasmosis. The team has applied their clinical and laboratory experiences to understand the infection and devise ways to prevent it, using immunology, genetics, bioinformatics and systems biology to develop and enhance the vaccine and make certain it can help humans worldwide.

“We now think we are reaching the next stage,” McLeod said. “Our toolbox could be developed to prevent and treat human T. gondii and P. falciparum infections.” This approach for vaccines, she added, “can generate innate immunity, cell-mediated adaptive immunity, and host-neutralizing antibodies that are critical to protect against different pathogens.”

References: El Bissati, K., Zhou, Y., Paulillo, S.M. et al. Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A11:01, HLA-A02:01 and HLA-B*07:02 transgenic mice. Sci Rep 10, 16984 (2020). https://doi.org/10.1038/s41598-020-73210-0

Provided by University Of Chicago Medical Center

The Mountains Of Pluto Are Snowcapped, But Not For The Same Reasons As On Earth (Planetary Science)

In 2015, the New Horizons space probe discovered spectacular snowcapped mountains on Pluto, which are strikingly similar to mountains on Earth. Such a landscape had never before been observed elsewhere in the Solar System. However, as atmospheric temperatures on our planet decrease at altitude, on Pluto they heat up at altitude as a result of solar radiation. So where does this ice come from? An international team led by CNRS scientists* conducted this exploration. They first determined that the “snow” on Pluto’s mountains actually consists of frozen methane, with traces of this gas being present in Pluto’s atmosphere, just like water vapour on Earth. Then, to understand how the same landscape could be produced in such different conditions, they used a climate model for the dwarf planet, which revealed that due to its particular dynamics, Pluto’s atmosphere is rich in gaseous methane at altitudes. As a result, it is only at the peaks of mountains high enough to reach this enriched zone that the air contains enough methane for it to condense. At lower altitudes the air is too low in methane for ice to form. This research, published in Nature Communications, could also explain why the thick glaciers consisting of methane observed elsewhere on Pluto bristle with spectacular craggy ridges, unlike Earth’s flat glaciers, which consist of water.

At left, the “Cthulhu” region near Pluto’s equator, at right the Alps on Earth. Two identical landscapes created by highly different processes. ©NASA/Johns Hopkins University Applied Physics Laboratory/Southwest Research Institute and Thomas Pesquet/ESA

*- Scientists from the IPSL Dynamic Meteorology Laboratory (CNRS / Sorbonne Université / École polytechnique / ENS Paris), the Institute for Planetary Sciences and Astrophysics of Grenoble (CNRS / Université Grenoble Alpes), the NASA Ames Research Center, and the Lowell Observatory (Unite States) took part in this research.

On Earth snow condenses at altitude because air dilates during ascending movements, and thus cools (at the rate of 1°C approximately every 100 m). On Pluto, methane ice forms on the peaks of mountains when they are high enough to reach upper atmospheric levels, which are hotter and rich in methane. ©Tanguy Bertrand et al.

References: Bertrand, T., Forget, F., Schmitt, B. et al. Equatorial mountains on Pluto are covered by methane frosts resulting from a unique atmospheric process. Nat Commun 11, 5056 (2020). https://doi.org/10.1038/s41467-020-18845-3 link: http://dx.doi.org/10.1038/s41467-020-18845-3

Provided by CNRS