Tech

Overview:

Associate Professor Hiroto Sekiguchi and Ph.D. candidate Hiroki Yasunaga in the Department of Electrical and Electronic Information Engineering at Toyohashi University of Technology have developed a MicroLED neural probe for neuroscience. This MicroLED tool can optogenetically control and observe neural activity in the brain. Neural activity was successfully recorded using the neural probe, and sufficient light output was obtained from the MicroLED to activate neural activity. The developed MicroLED tool will contribute to the development of neuroscience research-purposed optogenetic technology.

Details:

A research team in the Department of Electrical and Electronic Information Engineering at Toyohashi University of Technology has developed a MicroLED neural probe for neuroscience. This MicroLED tool can optogenetically control and observe neural activity in the brain. The neural activity was successfully recorded using the neural probe, and a light output that is sufficient to activate neural activity is obtained from the MicroLED. This probe will contribute to the development of neuroscience research-purposed optogenetic technology. The results of their research will be published in Japanese Journal of Applied Physics on December 16, 2020.

Advanced information processes are associated with higher brain functions and are the products of complex interactions between interconnected neurons. Optogenetic technology uses light to precisely target specific cells for manipulation without affecting other cells in the brain, which contributes to elucidating how neural activity and animal behaviors are linked. Although an optical fiber has been used as a photodelivery system, there are some issues with high invasion of the brain tissue and complex spatial control.

In the field of engineering, microLEDs, which are 1/10 or 1/100 of the performance of the conventional LED, have been attracting attention towards the realization of the high-brightness, highly efficient, and high resolution display. In this study, we have fabricated a new device that applies this small LED to brain science. The developed epoch-making neural probe tool can solve tasks in conventional neuroscience tools and can control and record the functions of different nerves in a complex area with a high spatiotemporal resolution.

The leader of the research team, Associate Professor Hiroto Sekiguchi, said, "We have been developing LED materials and MicroLED fabrication technology for more than 10 years, and LEDS are being industrialized. I have to find a new field to utilize LED technology. At one point, I met a pharmacy researcher in an encounter unrelated to research, and talked about research in a casual conversation. Half a year later, I received a consultation about this research, which led to the results of this research. I think that the simple and easy-to-understand explanations and the active interest in discussing themes in different fields has led to present research in the area of fusion of pharmacy and engineering."

The research team believes that the developed MicroLED neural probe would be useful as a tool for in vivo optogenetics research. If the mechanism of the brain is elucidated, the findings can be utilized in various fields, such as the establishment of treatment for cancer, psychiatric disorders, and epilepsy, application to brain-machine interface, and development of new algorithms based on brain function.

Severe thunderstorms often produce lightning, heavy precipitation, hails, and wind gusts, and cause significant economic losses and casualties in the region they passed through. So, their prediction is one of the primary concerns of not only weather forecasters but also local government and public. However, the accurate forecasting on severe thunderstorm is still a great challenge because of its complicated mechanism of formation and enhancement.

Beijing metropolitan region is one of the most developed areas in China and is also influenced greatly by severe thunderstorms. The complex terrain, dynamic and thermal characteristics of Beijing and its surrounding areas, as well as the multi-process and multi-scale interactions inside the thundercloud, make the development and propagation of the lightning weather system in Beijing very complicated.

"Efforts to understand the effects of complex thermal dynamics and microphysical characteristics on lightning, five consecutive years of collaborative observation experiments on severe convective thunderstorms were conducted in Beijing", said the fist author Xiushu Qie from the Institute of Atmospheric Physics, Chinese Academy of Sciences. "The primary detection equipment contains a 3D lightning location system - Beijing Lightning Network (BLNET), two X-band dual linear polarization Doppler radars and four laser raindrop spectrometers, etc. The data from the mesoscale meteorological observation network in Beijing operated by China Meteorological Administration was also utilized."

The researchers stated: "The lightning location data from the BLNET has the advantages of the 3D location of both intracloud and cloud-to-ground lightning with high-precision and being free from the terrain influences, providing new insights into the structure of the severe thunderstorms, especially the small-scale storm cells."

The researchers found that squall lines and multi-cell thunderstorms are the two main types of lightning disaster weather systems affecting Beijing. Lightning weather systems often generate and develop in the western and northern mountainous areas. The heat island effect and boundary layer characteristics of Beijing urban areas play important roles in the propagation and enhancement of thunderstorms passing over. The highest lightning density regions are in the east of Changping, the middle and east of Shunyi District, and the central city of Beijing. The lightning frequency of very strong thunderstorms can produce hundreds of lightning flashes per minute in the central Beijing.

Analyzing the lightning in thundercloud, the authors found that lightning mostly occurs in areas of strong convection and transition areas about 10 km away from the edge of strong convection, where the strong updraft or wind shift distributed. The growth and collision of ice-phase particles not only enhances the lightning process in the cloud, but also facilitates the generation of hailstones. The jump increase in lightning frequency can early warn the occurrence of hailfall and short-term heavy precipitation. The early warning time can reach nearly half an hour.

"By establishing the relationship between lightning frequency and the model parameters, such as water vapor mixing ratio, ice phase particle content, updraft velocity and radar reflection factor, lightning data can be assimilated into numerical weather prediction models at the cloud-resolved scale", the authors said. "Lightning data assimilation can significantly improve the forecast of severe convection and heavy precipitation".

Groundwater flow and seepage can form large gullies along coastal cliffs in the matter of days, it has been discovered, as per a recently-published paper.

An international team of scientists from Malta, Germany, Romania, New Zealand and USA has used drones and satellite imagery to monitor a stretch of coastline near Ashburton (South Island, New Zealand). They found that gullies up to 30m in length can develop in less than a week.

Field observations and numerical models have shown that groundwater plays a key role in forming these gullies, by either eroding tunnels or triggering landslides.

Gullies are an important coastal hazard. There is an average of one gully every 250m along the Canterbury coastline, and their formation leads to the loss of precious agricultural land.

Similar coastal gullies have been documented in South Taranaki (North Island, New Zealand), as well as other countries such as the USA, Japan and Brazil.

When and where coastal gullies form can be partly predicted. The study has shown that gullies form when more than 40mm of rain fall per day, and that they are preferentially located above buried, old river channels.

Researchers at the University of York are calling for more stringent regulatory measures to reduce the health burden of smokeless tobacco, a product often found in UK stores without the proper health warnings and as a result of illicit trading.

Smokeless tobacco is particularly popular in Asia and Africa and includes chewing tobacco as well as various types of nasal tobacco. They contain high levels of nicotine as well as cancer producing toxic chemicals, making head and neck cancers common in those who consume smokeless tobacco products.

In a study of 25 wards across five boroughs - Birmingham, Bradford, Blackburn, Leicester, and Tower Hamlets - researchers looked at the types of products sold in local shops and assessed their compliance with UK regulations.

They found that small amounts of smokeless tobacco are smuggled into the UK through domestic luggage, and larger amounts came through land and sea routes via Europe, whilst others are produced locally through small scale setups. In 52% of the local shops surveyed, products were sold under different brand names, none of which are legally permitted for sale in the UK.

Faraz Siddiqui, Research Fellow at the University of York's Department of Health Sciences, said: "Many people of South Asian origin use smokeless tobacco products, and it is particularly popular among women. Continued use of these products is known to lead to several oral and general health conditions, including cancers.

"It is imperative that smokeless tobacco products, which are directly implicated in head and neck cancers, are regulated in the same way that cigarette smoking is. And yet despite 181 countries agreeing to a common approach to controlling the demand and supply, there is still a serious lack of regulations in place."

The research, funded by Cancer Research UK, showed that almost half of identified products did not match packaging requirements. These were often sold in colourful packaging resembling confectionery items, and carried misleading information on taste and experience. Only 15% of these products were found to have health warnings.

Products were also considerably cheaper than cigarettes, and some varieties were available for as low as 70p. Approximately 18% of surveyed shopkeepers were aware of laws that applied to smokeless tobacco.

Professor Kamran Siddiqui, from the University's Department of Health Sciences, said: "In a study we conducted earlier this year, we found that the number of deaths globally due to smokeless tobacco has gone up by a third in just seven years to an estimated 350,000 people.

"Plain packaging and graphic health warnings applicable to cigarettes, for example, do not currently apply to smokeless tobacco, which is why we found so many products resembling sweet wrappers, readily accessible on shop countertops.

"Stricter laws and regulations of smokeless tobacco products in England are needed as a matter of urgency, as the absence of these policies will only see the health risks for South Asian people rise still further."

The researchers have suggested that a holistic approach to improving smokeless tobacco regulation could be the best way forward in communities with high numbers of South Asian people. This includes community engagement activities to raise awareness of health risks and offering dedicated cessation support services for smokeless tobacco in the same way that it is for smoking.

If you were an owner of a newly set-up company, you would most likely be focused on building brand awareness to reach out to as many people as possible. But how can you do so with budget constraints?

These days, businesses have turned to a select group of people who are active on social media platforms as a cost efficient way to drive their promotional efforts. Also referred to as 'influencers', they have the ability to influence the opinions or buying decisions of others.

The company would then focus their efforts on influencing the influencers, hoping that, in turn, their product information gets disseminated to the largest possible number of people through these influencers' wide social media networks.

This process, referred to as 'influence maximization' is well studied in social networks and computer science. Most often, one aspires to choose only a small number (let us call this k) of influencers, due to budget considerations.

The important questions to answer would then be; how do companies go about choosing these k influencers? How would they, in turn, model their behaviour? Does each of them influence their contacts independently or are their behaviours somehow linked? What are the computational implications?

Traditionally a popular model in influence maximization has been the independent cascade model wherein the assumption is that all the members in the network influence their contacts independently of others.

However, there could be hidden correlations in their behaviour which are not immediately evident.

In a study led by a team of researchers from the Singapore University of Technology and Design (SUTD), they computed the best k influencers, assuming the correlations between the way the members in the network behave is most detrimental to the company's interest. Thus the model assumed is of adversarial nature.

The team showed that such a model has computational benefits over an independent cascade model. They also performed a comparison of the set of seed agents chosen by their model versus the set chosen by the independent cascade model.

Their research work also provided a snapshot of their results from a sample network (refer to image).

"Evaluating and enhancing the robustness of networks to adversarial attacks will be important in various domains in the future. This work provides some useful computationally tractable models which can be used by practitioners, agencies and companies in such setups," said principal investigator Professor Karthik Natarajan from SUTD.

Photosynthesis, the process by which plants and other organisms convert sunlight into chemical energy, has been a major player during the evolution of life and our planet's atmosphere. Although most of the ins and outs of photosynthesis are understood, how the necessary mechanisms evolved is still a topic of debate. The answer to this question, however, may actually lie buried in the mineral world.

In a recent study published in Earth Science Frontiers (10.13745/j.esf.sf.2020.12.3), scientists from Peking University, China, shifted the focus in photosynthesis research from plants and bacteria one step further back to rocks and substances found in what's known as the "mineral membrane" of Earth. They propose that various components of this relatively thin layer, such as birnessite, goethite, and hematite, can also absorb energy from sunlight and channel it into chemical reactions. But how does this happen?

These semiconducting minerals are sensitive to specific wavelength of sunlight. When they absorb photons, electrons in lower energy states (valence band) are excited to jump into higher energy states (conduction band). The photoelectrons have sufficient energy to drive reduction reactions that would otherwise require external energy.

Surprisingly, this non-classical photosynthesis mechanism that occurs in widespread semiconducting minerals can catalyze reactions akin to those in biological photosynthesis found in cyanobacteria. For example, certain minerals can promote oxygen evolution (formation of dioxygen molecules) and carbon fixation (producing organic compounds using carbon atoms from inorganic sources). Moreover, these minerals may even act as photocatalysts for water splitting, which produces hydrogen and oxygen from water, and the conversion of atmospheric carbon dioxide into marine carbonate products. These processes combined might have played a transformative role throughout primitive Earth, causing noticeable changes in atmospheric and marine conditions to foster the evolution of early lifeforms.

Most importantly, the scientists noted that birnessite is structurally similar to the "Mn4CaO5 complex at the core of the photosynthesis systems of modern organisms. This manganese-containing compound, which performs water splitting upon absorbing sunlight, may have actually evolved as an analog to birnessite. Lead author Dr. Anhuai Lu explains, "Our work in this new research field on the mechanisms of interaction between light, minerals, and life reveals that minerals and organisms are actually inseparable." The scientists postulate that primitive bacteria would have depended on minerals like birnessite to convert sunlight into useful chemical energy at first, before slowly incorporating structural analogues into their cellular bodies throughout evolution.

A better understanding of non-classical photosynthesis will help scientists unravel the mysteries behind the evolution of life and the chemical composition of our planet as we know it. From a more practical standpoint, it will also aid in the development of efficient methods for harvesting solar energy. "We can use mineral photocatalysis to promote water splitting, thereby improving the efficiency of biophotosynthesis systems and leading to revolutionary technologies," remarks Dr. Lu.

From progress in eco-friendly applications to a deeper knowledge of the history of life, it is clear that there is much to gain from studying the natural interactions between sunlight and minerals. Contrary to how the old saying goes, there still seems to be many things new under the sun!

Scientists are combining artificial intelligence and advanced computer technology with biological know how to identify insects with supernatural speed. This opens up new possibilities for describing unknown species and for tracking the life of insects across space and time

Insects are the most diverse group of animals on Earth and only a small fraction of these have been found and formally described. In fact, there are so many species that discovering all of them in the near future is unlikely.

This enormous diversity among insects also means that they have very different life histories and roles in the ecosystems.

For instance, a hoverfly in Greenland lives a very different life than a mantid in the Brazilian rainforest. But even within each of these two groups, numerous species exist each with their own special characteristics and ecological roles.

To examine the biology of each species and its interactions with other species, it is necessary to catch, identify, and count a lot of insects. It goes without saying that this is a very time-consuming process, which to a large degree, has constrained the ability of scientists to gain insights into how external factors shape the life of insects.

A new study published in the Proceedings of the National Academy of Sciences shows how advanced computer technology and artificial intelligence quickly and efficiently can identify and count insects. It is a huge step forward for the scientists to be able to understand how this important group of animals changes through time - for example in response to loss of habitat and climate change.

Deep Learning

"With the help of advanced camera technology, we can now collect millions of photos at our field sites. When we, at the same time, teach the computer to tell the different species apart, the computer can quickly identify the different species in the images and count how many it found of each of them. It is a game-changer compared to having a person with binoculars in the field or in front of the microscope in the lab who manually identifies and counts the animals", explains senior scientist Toke T. Høye from Department of Bioscience and Arctic Research Centre at Aarhus University, who headed the new study. The international team behind the study included biologists, statisticians, and mechanical, electrical and software engineers.

The methods described in the paper go by the umbrella term deep learning and are forms of artificial intelligence mostly used in other areas of research such as in the development of driverless cars. But now the researchers have demonstrated how the technology can be an alternative to the laborious task of manually observing insects in their natural environment as well as the tasks of sorting and identifying insect samples.

"We can use the deep learning to find the needle in the hay stack so to speak - the specimen of a rare or undescribed species among all the specimens of widespread and common species. In the future, all the trivial work can be done by the computer and we can focus on the most demanding tasks, such as describing new species, which until now was unknown to the computer, and to interpret the wealth of new results we will have" explains Toke T. Høye.

And there is indeed many tasks ahead, when it comes to research on insects and other invertebrates, called entomology. One thing is the lack of good databases to compare unknown species to those which have already been described, but also because a proportionally larger share of researchers concentrate on well-known species like birds and mammals. With deep learning, the researchers expect to be able to rapidly advance knowledge about insects considerably.

Long time series are necessary

To understand how insect populations change through time, observations need to be made in the same place and in the same way over a long time. It is necessary with long time series of data.

Some species become more numerous and others more rare, but to understand the mechanisms that causes these changes, it is critical that the same observations are made year after year.

An easy method is to mount cameras in the same location and take pictures of the same local area. For instance, cameras can take a picture every minute. This will give piles of data, which over the years can inform about how insects respond to warmer climates or to the changes caused by land management. Such data can become an important tool to ensure a proper balance between human use and protection of natural resources.

"There are still challenges ahead before these new methods can become widely available, but our study points to a number of results from other research disciplines, which can help solve the challenges for entomology. Here, a close interdisciplinary collaboration among biologists and engineers is critical", says Toke T. Høye.

A group of scientists from Russia, China, and the United States predicted and then experimentally obtained barium superhydrides' new unusual superconductors. The study was published in Nature Communications.

Chemists and physicists have been hunting down room-temperature superconductors since the first half of the 20th century. Initially, high hopes were placed on metallic hydrogen, but solid metallic hydrogen can become superconducting only at extremely high pressures of several million atmospheres, as it later transpired. Chemists then tried adding other elements to hydrogen in the hope of attaining superconductivity by stabilizing the metallic state under less challenging conditions. Scientists, including the research team led by Skoltech Professor Artem R. Oganov, predicted and experimentally obtained a set of compounds with a huge number of hydrogen atoms, such as ThH9 and ThH10 PrH9, NdH7, NdH9, YH6, and so on. Yet, the race for higher hydrogen content in such bizarre hydrides and especially for higher superconducting transition temperature is still on.

In their latest study, scientists from Oganov's laboratory and their colleagues from China and the United States analyzed all possible barium hydrides using the unique theoretical approaches developed by Oganov and his students and implemented in their USPEX code. Finally, they selected BaH12, a compound with one of the highest hydrogen contents. The researchers obtained the compound experimentally, demonstrated its superconductivity, and studied its crystal structure. BaH12 turned out to be quite a remarkable compound with a structure formed by molecular groups of two and three hydrogen atoms and acting as a molecular superconductor. Thanks to its molecular structure, BaH12 is not a high-temperature superconductor: its critical temperature is -253 degrees Celsius. The study marks significant progress in understanding what structures may someday perform as room-temperature superconductors in real devices.

"On October 14, 2020, American scientists reported the discovery of a room-temperature superconductor, ushering in an era of room superconductivity. The new superconductor composition has not been disclosed, but its room-temperature superconductivity has been convincingly demonstrated. A century-long dream has come true! Recall that superconductivity was first observed in mercury at -269 degrees Celsius over 100 years ago. The new material is unlikely to have immediate practical applications, as it can only be synthesized in microscopic amounts under extremely high pressures of nearly three million atmospheres. We should continue searching for new materials and studying their properties so that we could someday figure out how to achieve room-temperature superconductivity under normal pressure," Oganov says.

Researchers from Skoltech and their colleagues have optimized data analysis for a common method of studying the 3D structure of DNA in single cells of a Drosophila fly. The new approach allows the scientists to peek with greater confidence into individual cells to study the unique ways DNA is packaged there and get closer to understanding this crucial process's underlying mechanisms. The paper was published in the journal Nature Communications.

The reason a roughly two-meter-long strand of DNA fits into the tiny nucleus of a human cell is that chromatin, a complex of DNA and proteins, packages it into compact but very complex structures. To study the way DNA is packaged, researchers worldwide have developed so-called chromosome conformation capture (3C) techniques, the most efficient of which is called Hi-C. Hi-C essentially catalogs all interacting fragments of a DNA strand via high-throughput sequencing.

Therein lies the problem, however: to work, Hi-C needs tens of micrograms of DNA, which means millions of cells, each with its unique spatial organization of chromatin, have to be averaged to get a snapshot that will inevitably miss some peculiarities of DNA packaging in single cells. Much like the 'average person' does not really exist, conventional Hi-C cannot tell you which of the multitudes of interactions actually happen in the same cell. Furthermore, this snapshot will hardly be useful in unraveling the physical processes that led to chromatin's particular 3D structure.

"We see certain structures, such as so-called Topologically Associating Domains, or TADs, in averaged contact maps, but we do not know whether they are artifacts of averaging or indeed exist in individual cells. Moreover, we know that cells even in one tissue may be quite diverse in terms of gene expression - so a natural question arises whether this diversity also exists on the structural level," says Mikhail Gelfand, Skoltech Vice President for Biomedical Research and a co-author of the new paper.

To overcome this hurdle and make the Hi-C process more suitable for single cells, researchers from several institutes advanced a single-cell Hi-C technique. The Skoltech team, led by Gelfand and assistant professor at the Skoltech Center of Life Sciences Ekaterina Khrameeva, took a challenge to optimize data processing for single-cell Hi-C and uncover the fundamental properties of Drosophila cells.

Their colleagues from the Institute of Gene Biology RAS and Lomonosov Moscow State University collaborate with researchers from French-Russian Interdisciplinary Scientific Center J.-V. Poncelet optimized the snHi-C procedure to make it suitable for experiments with Drosophila cells.

For the technique to work, the teams had to start with the same Hi-C steps of chemically 'freezing' the chromatin in place, strategically cutting the DNA and reassembling it so that fragments that were spatially close end up stitched together. But then, instead of using the DNA in bulk, they amplified the miniscule amounts of DNA from a single cell in each well using a polymerase from a phi29 bacteriophage. This phi29 polymerase is widely used in DNA amplification methods thanks to its ability to generate a lot of DNA from the tiniest of templates and make significantly fewer errors than other commonly-used polymerases.

However, it turned out that the handy DNA polymerase, while less error-prone, can still make random 'hops' between DNA molecules, creating artificial 'links' that Hi-C algorithms cannot distinguish from real interactions. So the researchers had to come up with an authenticity test, weeding out the random hops from real traces of interacting fragments.

They used their new technique on Drosophila cells to determine whether the fundamental ways of chromatin folding are the same across organisms. Earlier studies in mammalian cells pointed to the existence of TADs in average contact maps from Hi-C analysis, but not in individual cells. However, in Drosophila, single-cell data show that there are TADs in each particular cell. More research is needed to elucidate the biological mechanism that forms these stable domains, but the researchers suggest two models for these TADs. One implies that Drosophila chromatin is 'sticky' in a particular way, with different regions having different affinity to form contacts. The other, so-called loop extrusion mechanism, posits that large protein complexes create loops in the strand, bringing distant regions close together and creating a larger-scale structure.

"Perhaps, one of the most interesting questions to ask is whether chromatin folding rules are similar between different species of living organisms. Having single-cell Hi-C for the individual cells of Drosophila, we noticed that the genome of this insect is folded into domains, similar to the domains observed in single mammalian cells. However, these structures are much more ordered than in mammals," Aleksandra Galitsyna, PhD student at Skoltech and one of the paper's first co-authors, notes.

"We will continue studying chromatin architecture and dig into the mechanisms of loop and TAD formation. There are lots of unanswered questions in this area. We already know that these mechanisms might differ between some organisms, but what is the full picture of chromatin folding evolution? If we want to understand it at a sufficient scale, we would need to bridge gaps between well-studied organisms by resolving chromatin structure in the weird ones. To do that, we are already working on sponges, yeasts, and amoeba," Ekaterina Khrameeva says.

She adds that the team is also interested in how chromatin organization changes might be associated with the disease, organism development, and aging. "Assuming that chromatin architecture is tightly linked to gene expression, answering these questions might unravel the regulatory prerequisites of human development, aging, and disease," Khrameeva notes.

Announcing a new publication for Marine Life Science & Technology journal. In this research article the authors Hungchia Huang, Jinpeng Yang, Shixiang Huang, Bowei Gu, Ying Wang, Lei Wang and Nianzhi Jiao from Xiamen University, Xiamen, China and Sun Yat-Sen University, Guangzhou, China consider the spatial distribution of planktonic ciliates in the western Pacific Ocea: along a transect from Shenzhen (China) to Pohnpei (Micronesia).

Planktonic ciliates have been recognized as major consumers of nano- and picoplankton in pelagic ecosystems, playing pivotal roles in the transfer of matter and energy in the microbial loop. However, due to the difficulties in identification, the species composition of ciliate assemblages, especially for the small, fragile, and naked species that usually dominate the ciliate communities in the oceanic waters, remains largely unknown.

The authors sampled 22 stations along the transect from Shenzhen (China) to Pohnpei (Micronesia) for the enumeration of picoplankton and nanoflagellates. In addition, pigment analysis of major phytoplankton groups along with the measurements of environmental variables including temperature, salinity, and nutrients were also carried out. Ciliates were identified at species level using quantitative protargol stain to reveal the species composition and their distribution patterns from offshore to open ocean. Ciliate abundance was positively correlated with phosphate, silicate, and pico-sized pigmented eukaryotes (PPEs), whereas the biomass was closely related with PPEs, heterotrophic nanoflagellates, and chlorophytes. The ciliate communities were separated into four groups showing a nearshore to open ocean trend.

The authors identified the combination of silicate and pigmented nanoflagellates as the major factor driving the ciliate community composition. This close relationship between silicate and ciliate abundance and community structure needs further validation based on more data collected from oceanic waters. The study demonstrates the necessity of using techniques that can reveal the community composition at higher taxonomic resolutions in future studies on ciliates.

The first step in treating cancer is understanding how it starts, grows and spreads throughout the body. A relatively new cancer research approach is the study of metabolites, the products of different steps in cancer cell metabolism, and how those substances interact.

To date, research like this has focused mostly on cancerous tissues; however, normal tissues that surround tumors, known as the extratumoral microenvironment (EM), may have conditions favorable for tumor formation and should also be studied.

In a new study published in the journal PLOS ONE, researchers investigated the metabolites involved in the growth and spread of melanoma, a rare but deadly type of skin cancer. The study, led by Nicholas Taylor, assistant professor in the Department of Epidemiology and Biostatistics at the Texas A&M University School of Public Health, analyzed frozen tissue samples from melanoma patients at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. These included samples of primary melanoma and matching EM tissues as well as unmatched metastatic melanoma tissues (melanoma that had spread to other parts of the body).

Differences in the types and amounts of metabolites in these tissues could tell more about how melanoma grows and spreads and whether EM tissues are truly normal or more favorable for tumor development.

Taylor and colleagues noted 824 significant differences in metabolite amounts between matched primary melanoma and EM tissues and 1,118 differences between metastatic melanoma and EM samples. The researchers then analyzed some of the chains of chemical reactions, known as metabolic pathways, involved in melanoma initiation and growth.

Their pathway-level analysis found that malignant and EM tissues had significantly different amounts of certain metabolites, such as lactate. They also found that both primary and metastatic melanoma showed similar metabolite differences from EM tissues. The amounts of a metabolite involved mainly in the spread, or metastasis, of cancer would differ between primary and metastatic melanoma. Thus, the metabolites analyzed are likely responsible for tumor initiation and maintenance and not for metastasis.

In addition, Taylor and colleagues observed differences in metabolite amounts across tumors that point to the reversal of a phenomenon common in cancer cells in which lactate is produced through a metabolic pathway that does not need large amounts of oxygen. This phenomenon is beneficial for cancer cells growing in low-oxygen environments, such as inside tumors. The reversal of this phenomenon is supported in this study by evidence that lactate was produced using a different oxygen-dependent pathway. The researchers note that this evidence agrees with other recent studies that suggest the existence of the reversed effect.

This knowledge can help with the development of new ways to treat melanoma, such as new experimental therapies that disrupt the oxygen-dependent metabolic pathway observed in this study. Because that metabolic pathway can help supply energy for growing cancer cells, disrupting the pathway could help slow or stop tumor growth. The findings of this study also serve as a starting point for additional research into the metabolism of both cancer cells and surrounding tissues.

Stroke survivors who had ceased to benefit from conventional rehabilitation gained clinically significant arm movement and control by using an external robotic device powered by the patients' own brains.

The results of the clinical trial were described in the journal NeuroImage: Clinical.

Jose Luis Contreras-Vidal, director of the Non-Invasive Brain Machine Interface Systems Laboratory at the University of Houston, said testing showed most patients retained the benefits for at least two months after the therapy sessions ended, suggesting the potential for long-lasting gains. He is also Hugh Roy and Lillie Cranz Cullen Distinguished Professor of electrical and computer engineering.

The trial involved training stroke survivors with limited movement in one arm to use a brain-machine interface (BMI), a computer program that captures brain activity to determine the subject's intentions and then triggers an exoskeleton, or robotic device affixed to the affected arm, to move in response to those intentions. The device wouldn't move if intention wasn't detected, ensuring subjects remained engaged in the exercise.

Using robotics in rehabilitation isn't new, said Contreras-Vidal, co-principal investigator of the trial and a pioneer in noninvasive BMI systems. But robot-assisted exercise doesn't generally engage the user, which is critical for taking advantage of the brain's plasticity to allow patients to relearn movement.

"This project ensures the brain is engaged," he said. "We know that if the arm is moving, it's because they are commanding it to move. That's a very powerful concept."

By testing the subjects over a period of time before the trial began, researchers were able to ensure that any changes or improvements were due to the intervention. In addition to better arm movement, the researchers reported that the subjects also showed improvements in using their hands.

"This is a novel way to measure what is going on in the brain in response to therapeutic intervention," said Dr. Gerard Francisco, professor and chair of physical medicine and rehabilitation at McGovern Medical School at The University of Texas Health Science Center at Houston and co-principal investigator. "This study suggested that certain types of intervention, in this case using the upper robot, can trigger certain parts of brain to develop the intention to move. In the future, this means we can augment existing therapy programs by paying more attention to the importance of engaging certain parts of the brain that can magnify the response to therapy."

The trial was conducted at TIRR Memorial Hermann, where Francisco serves as chief medical officer and director of the NeuroRecovery Research Center. The project was a collaboration between UH, UTHealth, TIRR Memorial Hermann, Houston Methodist Research Institute and Rice University.

In addition to Francisco and Contreras-Vidal, who is also director of the BRAIN Center, a NSF Industry/University Collaborative Research Institute, researchers involved with the project include Nikunj A. Bhagat and Zachary Hernandez with UH; Nuray Yozbatiran and Rupa Paranjape with UTHealth; Dr. Zafer Keser, formerly with UTHealth; Jennifer L. Sullivan, Colin Losey and co-principal investigator Marcia K. O'Malley with Rice; and Dr. Robert Grossman with Houston Methodist Research Institute. O'Malley is also Director of Rehabilitation Engineering at TIRR Memorial Hermann.

It was funded by the National Institute of Neurological Disorders and Stroke and Mission Connect, part of the TIRR Foundation.

"Those of us who have studied the brain for so many years have anticipated that its powers, combined with robotics and the brain-machine interface, could offer unimaginable benefits to stroke survivors and other patients with brain injuries," said Grossman, professor of neurosurgery at Houston Methodist. "This study is just the beginning of what will be possible to treat stroke, spinal cord injuries and other traumatic brain injuries in the future."

The trial spanned a period of several years, partly because it took time to find subjects who met the criteria and were both interested in participating and able to make the required time commitment. Ultimately, 10 subjects between the ages of 41 and 71 were enrolled.

The therapy took place three times a week for four weeks. The final follow-up testing was conducted two months after therapy ended, and Contreras-Vidal said it's unclear if the benefits will persist long-term.

That leads to an ongoing project - Contreras-Vidal has a National Science Foundation grant to design a low-cost system that would allow people to continue the treatments at home.

"If we are able to send them home with a device, they can use it for life," he said.

The abundant presence of an enzyme known as low molecular weight protein tyrosine phosphatase (LMWPTP) in tumor cells has long been considered an indicator of cancer aggressiveness and metastatic potential. It is also known to perform important functions in cells under normal conditions, participating in both the proliferation process and the regulation of intracellular systems. Research continues on its role in cancer progression.

In Brazil, a group of researchers at the University of Campinas’s In Vitro Bioassay and Signal Transduction Laboratory led by Professor Carmen Veríssima Ferreira-Halder are studying the possibility of inhibiting this protein phosphatase to create novel opportunities for monitoring and treatment of cancer and other diseases.

“We believe inhibition of LMWPTP could contribute to the treatment of several diseases,” Ferreira-Halder said. “In our case, the focus is on cancer, but research shows it’s also associated with autoimmune diseases and diabetes, among others.”

Ferreira-Halder was principal investigator for the Thematic Project “Low molecular weight protein tyrosine phosphatase in colorectal cancer: from the bench to product generation”, supported by FAPESP and completed in June 2020.
The phosphatase favors the action of intratumor proteins that help tumors divide, migrate and establish metastasis. “For this reason we say it’s a ‘hub’, in the sense that it controls several processes which together make tumor cells resistant to treatment and able to migrate and establish metastasis,” she said.

A review article by the group published in Cellular and Molecular Life Sciences outlines 14 years of research on LMWPTP and its contribution to cancer treatment. “Our group was one of the first to show that this enzyme contributes to chemotherapy resistance in leukemia cells,” Ferreira-Halder said. “We also found that the more advanced the stage of the tumor, the larger the amount of the enzyme. With these discoveries as a basis, research conducted in collaboration with the group led by Professor Maikel Peppelenbosch at Erasmus University Medical Center in Rotterdam [Erasmus MC, Netherlands] validated the significance of LMWPTP to other types of cancer, such as prostate, colorectal and stomach cancer. This research showed us that LMWPTP not only weakens the response to chemotherapy drugs but is also associated with a greater capacity for metastasis.”

Druggable target

The review article, whose first author is Alessandra Valéria de Sousa Faria, also discusses the available substances that inhibit LMWPTP and the characteristics that make it difficult for drugs to be designed against it. Ferreira-Halder believes it is not yet possible to speak of treatment based on inhibition of LMWPTP, but the strategy can be used for other purposes.

“Our initial aim is to use this enzyme as a biomarker for the purpose of monitoring treatment, and also to use it to classify patients in terms of the severity of disease. In my view this can be done in a relatively short time,” she said. “As for treatment, a lot more work remains to be done. Professor Nunzio Bottini at the University of California San Diego [USA] has filed for a patent on a highly effective inhibitor that can be administered orally. Actually he and his group have synthesized several inhibitors, but they have only published one. Maybe we’re in for a surprise and a drug will be developed faster. Who knows?”

The main challenges to be faced in developing inhibitors are specificity – the drug must act specifically on LMWPTP, which is part of a family of some 100 highly similar phosphatases – and stability, so that the drug remains active in the organism. “Until Bottini and his group filed their patent application, all inhibitors acted on several members of the family,” Ferreira-Halder said.

Some of the substances mentioned in the review were developed for other purposes but also inhibit LMWPTP and could be used to treat cancer, according to Faria, who recently defended her doctoral thesis on how LMWPTP affects platelets, small cell fragments in the bloodstream that play a key role in clotting.

Platelets

Faria’s research on LMWPTP began with its role in colorectal cancer and platelet reaction in this microenvironment. “As our investigation of platelet biology progressed, we realized how much more knowledge of the enzyme’s action on platelets was needed,” she said.

The first part of the study consisted of verifying the action of LMWPTP and the protein tyrosine phosphatase 1B (PTP1B) on platelets, with regard to both metabolism and function. The second focused on the influence of platelets on the expression of LMWPTP in cells.

“The goal was to find out to what extent tumor cells may ‘educate’ platelets to support certain events, such as metastasis, for example, and conversely how far platelets ‘educate’ tumor cells to assure their survival and proliferation,” Faria explained.

For Ferreira-Halder, the relationship appears to be two-way. “However, the action of tumor cells probably predominates. They practically program platelets to work in their favor,” she said.

Collaborations

Ferreira-Halder and her group have collaborated with Peppelenbosch’s since 2004, but work on the Thematic Project completed in June began only 2016, she recalled, adding that experiments conducted by Emanuella Maria Barreto Fonseca and Cláudia de Lourdes Soraggi at Peppelenbosch’s laboratory provided a vitally important foundation for the initial hypotheses. Fonseca was supported by a postdoctoral fellowship from FAPESP. Soraggi was able to attend an overseas training course thanks to support from the University of Campinas (UNICAMP) via its Executive Vice Rectorship for International Relations.

“In our Thematic Project research, we were able to investigate the action of this phosphatase from various angles and validate the hypothesis of its role in other tumors besides chronic myeloid leukemia,” Ferreira-Halder said. “We wanted to uncover the mechanism of its action, and we now have a great deal of information about this action – not just inside but also outside the tumor, because we set out to see if LMWPTP also influenced the tumor’s microenvironment external to the cancer cells.”

Other research interests for the group during the project included: extracellular vesicles (nanometer-sized structures that play an important role in intercellular communication), with Stefano Piatto Clerici supported by FAPESP showing that LMWPTP regulates these vesicles; platelets, studied by Faria, also with a scholarship from FAPESP; and the TGF-beta signaling pathway, which is involved in many cellular processes such as proliferation and differentiation and was studied by Helon Guimarães Cordeiro.

The network of collaborators continued to expand, adding an expert in platelet biology (Sheila Siqueira Andrade at PlateInnove Biotech), and a hematologist and an oncologist at Erasmus MC (Moniek de Maat and Gwenny Fuhler respectively).

According to Ferreira-Halder, the Thematic Project has so far spawned 15 publications (eight articles and two book chapters, as well as five articles under peer review), and several other research fronts. A new project in the same line of research is currently being designed.

Journal

Cellular and Molecular Life Sciences

DOI

10.1007/s00018-020-03657-x

Understanding the immune systems of oysters and clams is important in monitoring the effects of pollution and climate change on the health of molluscan species and the potential impacts on the aquaculture industry. Their immune responses also can serve as indicators of changes in ocean environments.

A new study involving the University of Maine assessed immune responses in four economically important marine mollusc species -- the blue mussel, soft-shell clam, Eastern oyster, and Atlantic jackknife clam -- and identified new biomarkers relating to changes in protein function involved in novel regulatory mechanisms of important metabolic and immunological pathways.

The discovery will aid further biomarker identification to benefit the aquaculture industry and provides new understanding of how these pathways function in diverse ways in different animal species.

"These biomarkers reveal how several different physiological functions can be generated from a single protein sequence. This gives added value to an organism's physiology," says Tim Bowden, UMaine associate professor of aquaculture and co-author of the study published as the cover article in the December 2020 issue of the journal Biology.

Bowden, a researcher in UMaine's School of Food and Agriculture and Aquaculture Research Institute, conducted the study with United Kingdom colleagues Igor Kraev of the Open University and Sigrun Lange of the University of Westminster.

Oysters and clams play a critical role in the food chain, representing more than 7% of global marine capture fisheries products in 2018, according to the Food and Agriculture Organization of the United Nations. In the U.S., more than 82% of the 2018 total value for marine aquaculture was derived from clams, mussels and oysters. Understanding molluscan metabolism is a priority based on the role of marine mollusks in global ecosystems and their burgeoning commercial value.

In their study of post-translational protein modification, the researchers found that deimination, or conversion of the amino acid arginine into the nonstandard amino acid citrulline, affects multiple pathways involved in immunity, metabolism and gene regulation.

Deimination is known to play a role in human diseases such as Alzheimer's and Parkinson's.

Study findings suggest that the enzymes that regulate deimination in mammals, birds and reptiles, and bacteria, parasites and fungi also are active in molluscan pathways. Peptidylarginine deiminases, or PADs, which had not previously been reported in Mollusca, may in fact serve as a control switch for varied immune and metabolic pathways in Mollusca and across the phylogenetic tree, according to the research team.

The researchers documented species-specific variations in the size and distribution of extracellular vesicles (EVs) in the bivalves studied. EVs have multiple functions including transporting proteins, genetic cargoes and biomarkers into cells and mediating host-pathogen interactions, among others.

Further investigation of the physiological and immune-related roles of EVs and characterization of the biomarkers they transport is warranted to enhance understanding of regulatory mechanisms and pathways in Mollusca and to support the global aquaculture industry.

ORLANDO, Jan. 12, 2021 -Vehicles have evolved to become more efficient and sophisticated, but their fuel hasn't necessarily evolved along with them. The Department of Energy is determined to identify cleaner burning and renewable alternatives to gasoline, and through the work of two UCF researchers, the DOE is one step closer to that goal.

Research engineer Anthony C. Terracciano and Associate Professor Subith Vasu have developed a model that will help engine designers, fuel chemists and federal agencies determine whether certain biofuels should be implemented as an alternative fuel for vehicles.

The research was conducted as part of the DOE's Co-Optimization of Fuels and Engines initiative, better known as Co-Optima. Findings were recently published in Nature Scientific Reports.

"We worked with scientists from various U.S. government labs to come up with our research strategy," Vasu says.

In prior Co-Optima research, Vasu and his team tested five of the most promising biofuels, including ethanol. For this research, Vasu and his team studied the biofuel diisobutylene (DIB), a natural byproduct of sugar.

"DIB has been down selected due to its promise as a potential drop-in biofuel for gasoline engines based on a variety of factors including its cost of production, compatibility with existing infrastructure, fuel and combustion properties," Vasu says.

Using the Advanced Light Source, a powerful particle accelerator at the Lawrence Berkeley National Laboratory, they were able to identify 46 molecules that are present in the flames of DIB during ignition. This is the first time that DIB has been studied with this equipment.

"Our work specifically identifies the quantity of 46 molecules present within the DIB combustion environment just after ignition," Terracciano says. "This provides an unprecedentedly rich framework, which engineers and scientists can use to craft a complete understanding of the reaction environment using these DIB fuels."

The researchers investigated the two most common sources of DIB, which are the alpha and beta strands. They created a combustion event in a jet-stirred reactor, a volume that is continuously stirred, at fixed conditions. The chemical reactions were then inhibited to create a molecular beam that was bombarded with ultraviolet light from the ALS to generate ions.

This model may be readily implemented by any agency, and the knowledge will help fuel developers manufacture a product much quicker.

"Fuel chemistry for vehicles is complex from the design and considerations of engines, support infrastructure and emissions," Terracciano says. "Fuel engineers need to ensure that the sold fuels fit within the envelopes of the octane standard. By knowing the combustion properties of specific fuel components, blends can be manufactured with less empirical testing."