Brain

Base editors, which enable production of highly efficient targeted point mutations in genomic DNA without causing double-stranded DNA breaks, hold great promise for gene therapy in human disease and trait improvement in crop plants.

GAO Caixia's group from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences has been developing plant base editing technologies. The researchers showed that cytosine base editors (CBEs) induce unexpected genome-wide off-target mutations in rice in order to stimulate the worldwide genome editing community to correct them.

Recently, GAO's team created two new CBEs based on a truncated human APOBEC3 cytidine deaminase (A3Bctd) and developed a high-throughput assay for assessing sgRNA-independent deamination changes in plant CBEs.

They first developed a rapid, high-throughput and inexpensive method for assessing CBEs in plants (nSaCas9-mediated orthogonal R-loop assay). In this assay, the orthogonal CRISPR system, nSaCas9, was used to create ssDNA regions in plant cells that acted as targets for sgRNA-independent deamination changes. To assess the nSaCas9-mediated orthogonal R-loop assay, they compared it with the whole-genome sequencing (WGS) assay.

The consistent results indicate that the nSaCas9-mediated orthogonal R-loop assay provides a logical, rapid and high-throughput method for assessing the sgRNA-independent off-target activities of CBEs.

Then they created 16 A3Bctd deaminase variants by rational design and evaluated their on-target efficiency and the sgRNA-independent off-target activities. They tested these A3Bctd-BE3 variants using the R-loop assay and selected seven mutations associated with efficient on-target editing activity and reduced off-target activity. After that, they combined these mutations and produced nine new A3Bctd-BE3 variants with double or triple amino acid substitutions.

In this way, they obtained two new CBE variants, A3Bctd-VHM-BE3 and A3Bctd-KKR-BE3, which exhibited efficient on-target activity and markedly reduced sgRNA-independent off-target activity.

In addition, these two new CBEs behaved more precisely at their target sites, and mainly produced single and double C edits. Also, they validated the high specificity of A3Bctd-VHM-BE3 and A3Bctd-KKR-BE3 by WGS assay.

The scientific paper, entitled "Rationally designed APOBEC3B cytosine base editors with improved specificity," was online published in Molecular Cell on July 27.

The research was mainly supported by the National Transgenic Science and Technology Program, the Strategic Priority Research Program of the Chinese Academy of Sciences, and the National Natural Science Foundation of China.

ITHACA, N.Y. - Is there an unbreakable code?

The question has been central to cryptography for thousands of years, and lies at the heart of efforts to secure private information on the internet. In a new paper, Cornell Tech researchers identified a problem that holds the key to whether all encryption can be broken - as well as a surprising connection to a mathematical concept that aims to define and measure randomness.

"Our result not only shows that cryptography has a natural 'mother' problem, it also shows a deep connection between two quite separate areas of mathematics and computer science - cryptography and algorithmic information theory," said Rafael Pass, professor of computer science at Cornell Tech.

Pass is co-author of "On One-Way Functions and Kolmogorov Complexity," which will be presented at the IEEE Symposium on Foundations of Computer Science, to be held Nov. 16-19 in Durham, North Carolina.

"The result," he said, "is that a natural computational problem introduced in the 1960s in the Soviet Union characterizes the feasibility of basic cryptography - private-key encryption, digital signatures and authentication, for example."

For millennia, cryptography was considered a cycle: Someone invented a code, the code was effective until someone eventually broke it, and the code became ineffective. In the 1970s, researchers seeking a better theory of cryptography introduced the concept of the one-way function - an easy task or problem in one direction that is impossible in the other.

For example, it's easy to light a match, but impossible to return a burning match to its unlit state without rearranging its atoms - an immensely difficult task.

"The idea was, if we have such a one-way function, maybe that's a very good starting point for understanding cryptography," Pass said. "Encrypting the message is very easy. And if you have the key, you can also decrypt it. But someone who doesn't know the key should have to do the same thing as restoring a lit match."

But researchers have not been able to prove the existence of a one-way function. The most well-known candidate - which is also the basis of the most commonly used encryption schemes on the internet - relies on integer factorization. It's easy to multiply two random prime numbers - for instance, 23 and 47 - but significantly harder to find those two factors if only given their product, 1,081.

It is believed that no efficient factoring algorithm exists for large numbers, Pass said, though researchers may not have found the right algorithms yet.

"The central question we're addressing is: Does it exist? Is there some natural problem that characterizes the existence of one-way functions?" he said. "If it does, that's the mother of all problems, and if you have a way to solve that problem, you can break all purported one-way functions. And if you don't know how to solve that problem, you can actually get secure cryptography."

Meanwhile, mathematicians in the 1960s identified what's known as Kolmogorov Complexity, which refers to quantifying the amount of randomness or pattern of a string of numbers. The Kolmogorov Complexity of a string of numbers is defined as the length of the shortest computer program that can generate the string; for some strings, such as 121212121212121212121212121212, there is a short program that generates it - alternate 1s and 2s. But for more complicated and apparently random strings of numbers, such as 37539017332840393452954329, there may not exist a program that is shorter than the length of the string itself.

The problem has long interested mathematicians and computer scientists, including Juris Hartmanis, professor emeritus of computer science and engineering. Because the computer program attempting to generate the number could take millions or even billions of years, researchers in the Soviet Union in the 1960s, as well as Hartmanis and others in the 1980s, developed the time-bounded Kolmogorov Complexity - the length of the shortest program that can output a string of numbers in a certain amount of time.

In the paper, Pass and doctoral student Yanyi Liu showed that if computing time-bounded Kolmogorov Complexity is hard, then one-way functions exist.

Although their finding is theoretical, it has potential implications across cryptography, including internet security.

"If you can come up with an algorithm to solve the time-bounded Kolmogorov complexity problem, then you can break all crypto, all encryption schemes, all digital signatures," Pass said. "However, if no efficient algorithm exists to solve this problem, you can get a one-way function, and therefore you can get secure encryption and digital signatures and so forth."

PULLMAN, Wash. - An endangered aquatic insect that lives in icy streams fed by glaciers might not mind if the water grows warmer due to climate change.

A study published in Global Change Biology on July 22 found that mountain stoneflies can tolerate warmer water temperatures at least temporarily. In fact, they might even be stressed in their current extremely cold environments.

While the study goes against the prevailing theory that rising water temperatures will be devastating for the glacial stream insects, Scott Hotaling, co-lead author on the study, said this does not mean that global warming will be a win for mountain stoneflies.

"These species are likely still very much in peril," said Hotaling, a Washington State University post-doctoral researcher. "They live in these extreme areas for a reason. The problem is we don't fully understand what that reason is yet. The threats from warming and the loss of glaciers are likely more complicated, and potentially, it is not about physical factors. It might be about ecological factors."

In the study, Hotaling and his colleagues tested the thermal tolerance levels of several species of mountain stoneflies found in the Rocky Mountains, including Lednia tumana, which was listed under the U.S. Endangered Species Act in November 2019 due to the rapid loss of its glacial habitat.

The researchers collected larval specimens of the stoneflies from streams in Glacier and Grand Teton national parks. They then subjected some of the flies to increasingly warmer water temperatures.

All of the species had a maximum tolerance of more than 20 degrees Celsius (68 Fahrenheit), which is well above their normal range of below 10 degrees Celsius (50 Fahrenheit).

They found that the stoneflies that experienced warmer temperatures expressed "heat shock proteins" at the cellular level. These proteins are named because they were first described in relation to exposure to high temperatures, but heat shock proteins are also related to other stressful events including exposure to cold.

In this study, the researchers found these same proteins were expressed not only by stoneflies exposed to heat but also by those that were held at 3 degrees Celsius (37.4 Fahrenheit), a similar temperature to their normal conditions, indicating mountain stoneflies might be stressed in their usual cold temperature environments.

The study's findings raise a lot of questions, including why these insects are not found in warmer waters currently, said co-lead author Alisha Shah, a post-doctoral researcher from University of Montana.

"It is possible that these mountain stoneflies are just bad competitors, and they are pushed up to these higher elevations by stronger competitors who prefer somewhat warmer temperatures," said Shah.

The researchers tested the flies' ability to tolerate short-term spikes of temperature, imitating what might happen to a stream on a hot summer day. Hotaling and Shah are now investigating how stoneflies respond to living in warmer water for longer periods. So far, the stonefly nymphs appear to develop faster. Shah said it was hard to tell yet if that was good or bad for the stoneflies overall since faster development might mean they have more deformities or fewer eggs.
Hotaling and Shah are investigating these variables in a race to better understand the cold communities that live downstream of glaciers before they disappear.

"We're stuck between having so little knowledge about the ecology and physiology of what lives on or downstream of glaciers and having so little time," Hotaling said. "These are some of the most rapidly changing places on the planet, so the time we have to understand them is ticking by very quickly."

Washington, DC - July 24, 2020 - Research presented at ASM Microbe Online found that 43% of Staphylococcus bacteria found on exercise equipment in university gyms were ampicillin-resistant, with 73% of those isolates being resistant to multiple additional drugs. The late Xin Fan, Ph.D., and her student Chase A. Weikel of West Chester University (WCU) conducted the research in cooperation with WCU's John M. Pisciotta, Ph.D., associate professor of Biology.

According to the U.S. Centers for Disease Control and Prevention, roughly 120,000 S. aureus bacteremia cases resulted in 20,000 deaths in 2017. Skin abrasions are a common route of entry of pathogenic S. aureus strains. As highlighted by the ongoing COVID-19 pandemic, there is increasing public concern regarding communal areas as a bastion of infectious microorganisms.

Results of the study found 43% of 462 S. aureus isolates recovered from 45 different exercise equipment surfaces were ampicillin resistant. Of 60 representative ampicillin-resistant isolates, 73% were resistant to two or more additional drugs including erythromycin and sulfisoxazole.

"These results suggest regularly contacted surfaces in different recreational environments can harbor multi-drug resistant S. aureus (MDRSA) and should be disinfected frequently to best maintain public health and community wellbeing," said Chase A. Weikel, a 2018 graduate of West Chester University and current graduate student at Thomas Jefferson University in Philadelphia.

Samples were collected from 2 university recreational facilities. The surfaces gym patrons frequently touched, including dumbbells and barbell handles, cable pull grips, kettlebells, elliptical and treadmill handles were swabbed and plated on Mannitol Salt Agar (MSA). This selective and differential media was used to isolate and presumptively identify S. aureus. Isolates were replicated to MSA plus ampicillin. Isolates additionally resistant to oxacillin or penicillin were subsequently screened using CHROMagar™ MRSA; a sensitive and specific media used to screen for methicillin-resistant S. aureus (MRSA). Isolates that tested positive using CHROMagar™ were subjected to additional confirmatory methods including latex agglutination assay. Microscopy was used to confirm Gram-positive status and cellular morphology and arrangement.

This research is being presented as an ePoster at the ASM Microbe conference which is proceeding in an on-line format in August 2020. ASM Microbe Online brings you the dynamic, cutting-edge science of ASM Microbe 2020, the annual meeting of the American Society for Microbiology. Explore the latest research in the microbial sciences with ePosters, hear from experts in the field during live keynotes and access track-related content with a curated selection of on-demand sessions.

Cell division is a fundamental process that organisms need to reproduce, grow, and make repairs. But when an error disrupts this complex biological process, cellular abnormalities can lead to diseases, such as cancer, where cells are enabled to grow and divide out of control.

Using a combination of experiments and mathematical modeling, a team of researchers from the Virginia Tech Department of Biological Sciences in the College of Science and the Fralin Life Sciences Institute are beginning to unravel the mechanisms that lie behind tetraploidy - a chromosomal abnormality that is often found in malignant tumors.

Their findings were published on April 29 in eLife, an open-access journal that is dedicated to life science research.

“Our study used fixed cell analysis, live cell imaging, and mathematical modeling to help us better understand the role of tetraploidy in tumor formation and progression. This work lays the foundation for future studies to really understand the link between tetraploidy and cancer. If we know what is happening in tumors, then we can have a better idea of how to develop better treatments for them,” said Nicolaas Baudoin, the lead author on the study and a recent Ph.D. graduate in the Department of Biological Sciences and the BIOTRANS program, an interdisciplinary graduate program of biologists and engineers.

Every human ‘parent’ cell holds two copies of each chromosome. Before cell division begins, every chromosome is duplicated so that the genetic information can be equally distributed between two ‘daughter’ cells. But if the parent cell fails to complete cell division, all four chromosomes are allocated into one daughter cell, thus making the cell tetraploid.

When tetraploid cells acquire twice the number of chromosomes, they also acquire twice the number of centrosomes. Among their organizational and structural roles, centrosomes are key to forming microtubules and spindle fibers, which work to pull chromosomes apart during cell division. With the overabundance of centrosomes, the chromosomes are pulled in many different directions and cell division can have abnormal results.

Previous studies had suggested that these extra centrosomes may cause tumor formation, induced by tetraploidy. But then, the Virginia Tech team came across two studies in cancer progression models, which showed that the cells gained extra centrosomes initially, but ended up losing them over time.

“The main goal of our study was to verify that tetraploid cells lose the extra centrosomes, examine the dynamics of this process, and uncover the mechanism that causes this centrosome loss from tetraploid cells,” said Daniela Cimini, a professor from the Department of Biological Sciences and the co-director of BIOTRANS.

Using live cell imaging and fixed cell analysis in an in vitro model, the team confirmed that tetraploid cells did lose the extra centrosomes that they had gained during tetraploidization.

In experiments guided by mathematical modeling, they concluded that centrosome loss happens when dividing tetraploid cells cluster their extra centrosomes asymmetrically. As a result, one of the daughter cells will inherit one centrosome - instead of two - which will allow the cell to suffer fewer cell division failures and produce more cells in the long term.

This finding can explain how certain cancers may first gain extra centrosomes during tetraploidization, but then lose them at later stages. This indicates that the causal relationship between tetraploidy and cancer needs further investigation.

The mathematical model also found that the only cells that could sustain long-term survival with extra centrosomes were cells that could successfully and consistently cluster these centrosomes in two groups during cell division. These predictions were tested experimentally and revealed a mechanism that explains why certain cancer cells survive despite their additional centrosome count. And if cells failed to cluster their extra centrosomes effectively, the next generation of daughter cells died.

Baudoin and Cimini agree that this level of mechanistic understanding was only possible thanks to their collaboration with Jing Chen, a mathematical biologist and assistant professor of biological sciences in the Virginia Tech College of Science.

“Built upon experimental measurements, the mathematical model paints a continuous and detailed picture about how the cells’ centrosome numbers change. This allows us to see information that cannot be measured by experiments.” said Chen, an affiliated faculty member of the Fralin Life Sciences Institute and BIOTRANS.

Next, the team would like to take advantage of their model to better understand the cellular dynamics within three-dimensional cultures and real tumors.

In their in vitro system, the team could get a sense of what was happening within the cells by tracking and imaging them, but this cannot be done in more complex systems like real tumors. With their newest model and previous data, the team will be able to make some compelling predictions.

According to Chen, the success of present and future cancer studies could be attributed to a unique, but all important, collaboration between researchers in the fields of biology and mathematics.

“This hand-in-hand collaboration between experimentalist and modeler is very important - and it’s a great approach for modeling biological studies. The process requires a lot of close communication between us. When that’s done correctly, it can be very powerful,” said Chen.

DOI

10.7554/eLife.54565

Chestnut Hill, Mass. (7/24/2020) - Converting carbon dioxide to methanol, a potentially renewable alternative fuel, offers an opportunity to simultaneously form an alternative fuel and cut down on carbon dioxide emissions.

Inspired by naturally occurring processes, a team of Boston College chemists used a multi-catalyst system to convert carbon dioxide to methanol at the lowest temperatures reported with high activity and selectivity, the researchers reported in a recent online edition of the journal Chem.

The team's discovery was made possible by installing multiple catalysts in a single system constructed within a sponge-like porous crystalline material known as a metal-organic framework, said Boston College Associate Professors of Chemistry Jeffery Byers and Frank Tsung, lead authors of the report.

Held in place by the sponge, the separate catalysts work in harmony. Without isolation of the catalytically active species in this way, the reaction did not proceed and no product was obtained, they reported.

The team drew its inspiration from the biological machinery in cells, which use multicomponent chemical reactions with great efficiency, Tsung said.

The team employed catalyst separation through host-guest chemistry - where a "guest" molecule is encapsulated in a "host" material to form a new chemical compound - in order to convert carbon dioxide to methanol. The approach, inspired by the multicomponent catalytic transformations in nature, converted a greenhouse gas to a renewable fuel while avoiding high catalytic demand on a single species.

"We accomplished this by encapsulating one or more catalysts in metal-organic framework and applying the resulting host-guest construct in catalysis in tandem with another transition metal complex," said Tsung.

The team, which included graduate student Thomas M. Rayder and undergraduate Enric H. Adillon, set out to determine whether they could develop an approach to integrate incompatible catalysts in order to convert carbon dioxide to methanol at low temperature and with high selectivity, said Byers.

Specifically, they wanted to find out if there are specific advantages to this approach when compared to current state of the art systems for transition metal complex-based conversion of carbon dioxide to methanol.

"Positioning multiple transition metal complex catalysts at the right position in a system is critical to the reaction turning over," said Byers. "At the same time, encapsulating these catalysts allowed for recyclability in the multicomponent catalytic system."

These properties make the multicomponent catalyst construct more industrially relevant, which may pave the way for a carbon-neutral fuel economy, the researches said.

In addition to achieving site isolation by encapsulating the catalysts, which led to catalyst activity and recyclability, the team discovered an autocatalytic feature of the catalyst that enabled the reaction to be run without the need for large amounts of additives. Most previous reports for similar reactions use large amounts of additives, but the team's approach avoids this necessity.

The team plans to do further research into the modularity of both the encapsulation method and the metal-organic frameworks to gain a deeper understanding of the multicomponent system and optimize it further, as well as access new, unexplored reactivity through the formation of new host-guest constructs, Tsung said.

WASHINGTON, July 23, 2020--A new analysis by The Pew Charitable Trusts and SYSTEMIQ finds that without immediate and sustained action, the annual flow of plastic into the ocean could nearly triple by 2040. But the study also identifies solutions that could cut this volume by more than 80 per cent using technologies that are available today, if key decision-makers are willing to make system-wide changes.

The findings from the scientific analysis were released today in a report, "Breaking the Plastic Wave: A Comprehensive Assessment of Pathways Towards Stopping Ocean Plastic Pollution." The release coincides with the July 23 publication of the technical underpinnings of the report in an article in the journal Science, "Evaluating Scenarios Toward Zero Plastic Pollution."

The research found that if no action is taken to address the projected growth in plastic production and consumption, the amount of plastic entering the ocean each year would grow from 11 million metric tons to 29 million metric tons over the next 20 years, equivalent to nearly 50 kilograms (110 pounds) of plastic on each metre of coastline worldwide. Because plastic remains in the ocean for hundreds of years and may never truly biodegrade, the cumulative amount of plastic in the ocean by 2040 could reach 600 million tons--equivalent in weight to more than 3 million blue whales. And COVID-19 has presented additional challenges in the fight to end ocean-bound plastic pollution, as single-use plastic consumption has increased during the pandemic, according to the International Solid Waste Association.

Working with scientists and experts around the world, Pew and SYSTEMIQ reached the report's conclusions using a first-of-its-kind economic model that quantifies the flow and amount of plastic in the global system and compares the quantity of ocean plastic pollution between 2016 and 2040 under six scenarios: from no change from the projected rising flow of plastic into the ocean (noted in the report as "business-as-usual") to a total overhaul (called the "system change scenario") of the world's plastics system, including its production, collection, consumption, and disposal/recycling. The model quantifies the associated cost, climate, and employment implications of each scenario.

Although progress has been made in addressing the global plastic challenge, the report finds that current commitments by government and industry will reduce the amount of plastic flowing into the ocean only by 7 per cent by 2040. And without meaningful change, about 4 billion people worldwide are likely to be without organized waste collection services by 2040, contributing significantly to the projected amount of ocean plastic pollution; closing this gap would require connecting more than 500,000 people to collection services per day until 2040.

"Breaking the Plastic Wave" identifies eight measures that together could reduce by 2040 about 80 per cent of the plastic pollution that flows into the ocean annually, using technology and solutions available today. Among them are reducing growth in plastic production and consumption, substituting some plastics with alternatives such as paper and compostable materials, designing products and packaging for recycling, expanding waste collection rates in middle- and low-income countries, increasing recycling, and reducing plastic waste exports. In addition to improving ocean health, adopting the changes outlined in the report could generate savings of USD$70 billion for governments by 2040, relative to business-as-usual; reduce projected annual plastic-related greenhouse gas emissions by 25 per cent; and create 700,000 jobs.

While the system change scenario reduces annual ocean plastic pollution rates by more than 80 per cent, it will take an unprecedented level of action and will still leave more than 5 million metric tons leaking into the ocean each year in 2040. Fully eliminating the flow of ocean plastic pollution will require dramatically increasing innovation and investment, with significant technological advances, new business models, and a greater emphasis on research and development.

"There's no single solution to ocean plastic pollution, but through rapid and concerted action we can break the plastic wave," said Tom Dillon, Pew's vice president for environment. "As this report shows, we can invest in a future of reduced waste, better health outcomes, greater job creation, and a cleaner and more resilient environment for both people and nature."

Plastic pollution presents a unique challenge for producers and users of virgin, or new, plastics given regulatory changes, such as bans on single-use plastic items, and growing consumer concern about the impact of plastic waste in the environment. But it is also a unique opportunity for providers of new and existing materials and industries that use circular business models and reuse and refill systems, which are designed to keep products and materials in use for as long as possible.

"Our results indicate that the plastic crisis is solvable. It took a generation to create this challenge; this report shows we can solve it in one generation," said Martin Stuchtey, SYSTEMIQ's founder and managing partner. "'Breaking the Plastic Wave' leaves no viable excuse on the table; we have today all the solutions required to stem plastic flows by more than 80 per cent. What we now need is the industry and government resolve to do so."

BOSTON - New genome-editing technologies developed by researchers in J. Keith Joung's laboratory at the Massachusetts General Hospital (MGH) have the potential to help understand disease-associated genetic mutations that are based on C-to-G (cytosine to guanine) single base changes. The new base editors are also designed to minimize unintended ("off-target") mutations that could potentially cause undesirable side effects.

The new CRISPR-guided DNA base editing technologies are designed to efficiently induce "transversion" alterations of DNA bases while minimizing levels of unwanted "bystander" mutations.

The proof-of-concept C-to-G base editor, called CGBE1, and a smaller version, miniCGBE1, are described in a paper by co-first authors Ibrahim C. Kurt and Ronghao Zhou that was published online in the journal Nature Biotechnology.

CRISPR (clustered regularly interspaced short palindromic repeats) is a gene-editing technology first discovered as a defense mechanism in bacteria and then harnessed by scientists as a tool for snipping out and/or repairing DNA sequences. The first CRISPR techniques relied on creating and repairing double-strand DNA breaks.

"Base editing is a new form of CRISPR gene editing that was developed by David Liu's lab at Harvard University and the Broad Institute. It is not based on introducing a double-stranded break in DNA, but is rather focused on directly changing a single base in DNA," explains co-corresponding author Julian Grünewald, MD, of the MGH Molecular Pathology Unit and Harvard Medical School (HMS).

Base editors are fusion proteins that use a modified form of CRISPR-Cas that is targeted to a specific target site with the help of a guide RNA, where it then deploys an enzyme called a deaminase to modify a specific base to create a desired DNA change. For example, the technique can be used to convert a cytosine (C) base to a thymine (T) base, both bases within the pyrimidine class (performed with a cytosine base editor, or CBE). Similarly, an adenine base editor (ABE) is capable of converting an adenine (A) to a guanine (G), both being purine bases.

CGBE1 leverages a CBE variant that was published in 2019 by J. Keith Joung, MD, PhD and colleagues in Nature. This earlier CBE variant, called SECURE-CBE, was shown to induce C-to-T changes with markedly fewer off-target RNA effects.

The new CGBE1 tool incorporates the deaminase from this SECURE-CBE variant, which together with other components enables the technically challenging swapping of bases from one class to another while still minimizing the risk of unwanted changes.

"There are known disease-associated mutations or pathogenic mutations that could be fixed by this type of editing," Grünewald says.

However, the exact number of diseases that might be correctable with CGBE1 or a similar editing platform is unclear.

"We're still at an early stage with this new class of transversion base editors; CGBE1 still requires additional optimization and it would be premature to say this is ready for the clinic. But we envision that CGBE1 could be useful for research applications, enabling the introduction of specific C-to-G mutations," he says.

A healthy low-calorie diet that contains plant products can help us improve the level of sirtuin 1 (SIRT1) protein production that is known to increase life expectancy. A team of scientists from Krasnoyarsk conducted an experiment to see how buckwheat affected the health of rats. The only known method to optimize the level of this protein is a calorie restriction. But why will healthy people be subjected to calorie restriction without any medical emergency? According to the researchers, a buckwheat-based diet helps to increase the level of SIRT1 protein that protects all the cells of the body and enhances longevity. In the same time, there is no need to starve. The results of the study were published in the Journal of Cereal Science.

With increased stress levels and wide availability of junk food, today we have to take special care about our health. Vitamins and amino acids are precursors of important regulatory and building molecules in our bodies, and a diet rich in them can help keep one's digestive system healthy and support it in case of any health issues. On the contrary, an unbalanced diet or overeating can cause various diseases, including cancers.

SIRT1 is a protein that senses nutrient status of cells. When SIRT1 levels in a cell are intentionally increased, its aging process slows down, and its stress resistance improves. However, the excess of SIRT1 in the organs and tissues of a living being is a sign of hunger which may lead to anemia and other negative effects.

A team of biologists from the School of Fundamental Biology and Biotechnology of Siberian Federal University added 30% buckwheat (which is rich in nutrients) to the diet of rats and studied its impact on their health. The animals were divided into three groups with eight rats in each. The first (control) group got a regular amount of feed; in the second (calorie restriction group) the portions were reduced by 30%, and the third (experimental) group got regular feed with the addition of ground buckwheat that amounted up to 30% of the total feed weight. Buckwheat contains dietary fiber that could be only partially digested by humans and rats. In view of that, the scientists calculated the daily feed volume for the third group for it to have the same nutritional value as the diet of the second group.

After eight weeks of the experiment, samples were taken from the blood, liver, kidneys, and stomach of the animals to measure the content of SIRT1. To do so, the scientists used molecules that produce a colored substance after linking with SIRT1. Moreover, the team monitored the weight of the rats in the course of the experiment. The animals from the third group gained more weight than the ones from the second group, even though both groups consumed an equal amount of calories. This observation indicates that buckwheat ensures proper growth and development in the long run. Though the highest level of SIRT1 production was registered in the calorie restriction group. However, this effect was achieved at the cost of lowering body and organ weights. In the experimental group the levels of the protein were higher than in the control group, but no weight loss was observed.

"The results of the study show that a diet that includes buckwheat has the effect of calorie restriction, because this grain contains a lot of indigestible fiber. Buckwheat is a low calorie product, and when added to a diet, it increases the production of SIRT1. This protein, in turn, protects the cells of the digestive system without causing hunger and loss of growth in animals. We believe that other plant products, such as grain, vegetables, fruit, or nuts, have similar effect on SIRT1 production and on the health in general. If you want a healthy and long life, eat more of them", said Shubhra Pande, the author of the research and the Post-doctoral fellow of the Department of Biophysics at the School of Fundamental Biology and Biotechnology of Siberian Federal University.

What factors influence the spread of invasive animal species in our oceans? This question was the focus for a team of experts from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI), Bangor University (Wales, UK), and the University of Greifswald's Zoological Institute and Museum in the context of the DFG-sponsored Research Training Group 2010 RESPONSE (Biological Responses to Novel and Changing Environments). The results of their study have just been released in the journal Ecography (DOI: 10.1111/ecog.04725).

Crustaceans dominate the food webs of many costal habitats in our oceans. In addition, as 'stowaways' on board of vessels used in global shipping, many crab species have spread far beyond their natural homes. The Asian shore crab Hemigrapsus sanguineus is a good example of these invasive species: in just a few decades this species, native to the Pacific, has spread to many corners of the globe. By the 1980s, it had made its way to the Atlantic coast of North America, and by the 1990s, had gained a foothold in the coastal waters of Europe. In both North America and Northern Europe, this species is spreading farther and farther north, toward the rapidly warming polar waters. In the ecosystems they invade, these crabs can soon reach such high numbers that native species like the European shore crab Carcinus maenas are impacted or displaced. Furthermore, they exert considerable predation pressure in their new homes, often decimating e.g. marine invertebrates like mussels or young shore crabs, and taking these food sources away from other species in the process. This can produce lasting changes to the invaded ecosystems.

But how is climate change influencing the spread of invasive marine species? Invasive species are often characterised by a high tolerance for fluctuations in environmental factors like temperature and salinity, thus being more adapted to the effects of climate change in the oceans. The team of researchers, including members from the Alfred Wegener Institute, Bangor University (Wales, UK) and the University of Greifswald, especially focused on the early developmental stages of the Asian shore crab, and examined its microscopically small larvae, which grow as they float in the water column. Since it has been confirmed that the larvae of many marine organisms are more sensitive to environmental fluctuations than their adult counterparts, these larvae often represent a 'bottleneck' in the establishment of new populations.

In addition, the study sought to develop models for predicting the speed at which the Asian shore crab could spread northwards, taking climate warming into account. The project's main question: Are findings regarding seasonal influences on larval development helpful for such forecasts? In the study, the team began by measuring the larvae's developmental parameters, e.g. the survival rate and time needed for development at different water temperatures. For this purpose, at the AWI's facilities on Helgoland they studied the duration of their young developmental stages in the lab; and they investigated the occurrence of crab larvae in the field. With the aid of a mechanistic model, the authors were then able to determine the timeframe during the mating season in which the water temperature needs to be above a certain threshold in order for the larvae to successfully develop into juvenile crabs. This modelling indicates considerable potential for the Asian shore crab to spread farther north, along the coasts of Northern England and Norway.

According to AWI biologist Dr Gabriela Torres and Dr Luis Giménez, a fellow biologist at the AWI and first author: "Our study confirms that, when it comes to predicting the climate-related spread of marine fauna, we need to especially focus on the early stages of development, as they are critical for the settlement on new habitats and the establishment of new permanent populations." Prof Steffen Harzsch from the University of Greifswald's Zoological Institute and Museum adds: "The Research Training Group RESPONSE offers us an outstanding platform for scientifically investigating various aspects of climate change, through interdisciplinary collaborations that reach far beyond Greifswald."

The perceived "whiteness" of Americans of Middle Eastern and North African descent is indirectly tied to discrimination against them, and may feed a "negative cycle" in which public awareness of discrimination leads to more discrimination, according to a Rutgers-led study.

The study, published in Social Psychological and Personality Science, points out a tension between the fact that Middle Eastern and North African Americans are instructed to select "white" on U.S. Census forms, although they are culturally perceived as not being white.

"Middle Eastern and North African Americans are left in a precarious position of not being legally classified as a racial minority group, while at the same time not being able to fully occupy the white racial category," said study co-author Kimberly Chaney, a doctoral graduate student in social psychology at Rutgers University-New Brunswick's School of Arts and Sciences.

The researchers reviewed the extent to which discriminatory attitudes toward Middle Eastern and North African Americans is tied to the perception of them as white or not white.

A group of white adults were asked whether they supported discriminatory policies such as "America would be safer if we prevent Middle Easterners from entering the country" or "America would be safer if there was a registry of Middle Easterners." Then they were shown faces with a range of complexions, and asked to indicate which one most represented Middle Eastern Americans.

Those who saw Middle Eastern Americans as typically white were less likely to support discriminatory practices against them. Those who viewed Middle Eastern Americans as less typically white were more likely to support discriminatory policies.

The researchers also examined whether highlighting the discrimination faced by Middle Eastern and North African Americans would shift perceptions of them. After reading an article about discrimination against Middle Easterners in the United States, a group of white adults were more likely to perceive Middle Eastern Americans as not being white. But the researchers noted that if awareness of discrimination leads white Americans to see Middle Easterners as "less white," this perception may, in turn, lead to more discrimination.

"It is a negative cycle of exclusion and discrimination," said Diana Sanchez, a professor of psychology.

The next step for the research would involve examining Middle Eastern and North African Americans' own experiences and self-identities, the researchers said.

Science has shown that service dogs can benefit some veterans with PTSD. But the exact role service dogs play in the day-to-day lives of veterans - and the helpfulness of the tasks they perform - is less known.

A recent study led by Purdue University's College of Veterinary Medicine shows what trained tasks service dogs perform the most often and which ones are the most helpful to veterans with post-traumatic stress disorder. The study found that the task of disrupting episodes of anxiety ranked among the most important and most often used.

"There has been some debate on what kind of training PTSD service dogs need to be effective and how their assistance may be different than what a pet dog can provide," said Kerri Rodriguez, a human-animal interaction graduate student and a lead author on the study. "This study suggests that veterans are, in fact, using and benefiting from the specific trained tasks, which sets these dogs apart from pet dogs or emotional support dogs."

Rodriguez led the work with Maggie O'Haire, associate professor of human-animal interaction. Their research was published in Frontiers in Psychology. The study was done in conjunction with K9s For Warriors, with support and funding from Merrick Pet Care, and is in preparation for an ongoing large-scale clinical trial that is studying veterans with and without service dogs over an extended period of time.

The study found that, on average, the dog's training to both alert the veteran to any increasing anxiety and providing physical contact during anxiety episodes were reported to be the most important and the most often used in a typical day. Veterans with a service dog also rated all of the service dog's trained tasks as being "moderately" to "quite a bit" important for their PTSD.

Some trained tasks include picking up on cues veterans display when experiencing distress or anxiety and consequently nudging, pawing or licking them to encourage the veteran to focus on the dog. The service dogs also are trained to notice when veterans are experiencing anxiety at night and will actively wake up the person from nightmares.

The dogs also are trained to perform tasks in public - such as looking the opposite way in a crowded room or store to provide a sense of security for the veteran.

The study also found that trained service dog tasks were used on average 3.16 times per day, with individual tasks ranging from an average of 1.36 to 5.05 times per day.

Previous research led by Rodriguez showed that the bond between a service dog and the veteran was a significant factor in the importance of untrained behaviors. Although all trained tasks were reported to be important for veterans' PTSD, those with a service dog actually rated the importance of untrained behaviors higher than the importance of trained tasks. This suggests that there are some therapeutic aspects of the service dog's companionship that are helping just as much, if not more, than the dog's trained tasks, Rodriguez said. "These service dogs offer valuable companionship, provide joy and happiness, and add structure and routine to veterans' lives that are likely very important for veterans' PTSD."

The study surveyed 216 veterans from K9s For Warriors, including 134 with a service dog and 82 on the waitlist. The study complements a previous publication published last year that focused specifically on the service dogs' training, behavior and the human-animal bond.

While service dogs were reported to help a number of specific PTSD symptoms such as having nightmares, experiencing flashbacks, or being hyperaware in public, there were some symptoms that service dogs did not help, such as amnesia and risk-taking.

"Both this research, as well as other related studies on PTSD service dogs, suggest that service dogs are not a standalone cure for PTSD," O'Haire said. "Rather, there appear to be specific areas of veterans' lives that a PTSD service dog can help as a complementary intervention to other evidence-based treatments for PTSD."

Veterans on the waitlist to receive a service dog expected the service dog's trained tasks to be more important for their PTSD and used more frequently on a daily basis than what was reported by veterans who already had a service dog.

"Veterans on the waitlist may have higher expectations for a future PTSD service dog because of feelings of hope and excitement, which may not necessarily be a bad thing," Rodriguez said. "However, it is important for mental health professionals to encourage realistic expectations to veterans who are considering getting a PTSD service dog of their own."

America's oldest citizens say they've been through worse, but many older adults are feeling the stress of COVID-19 and prolonged social distancing measures, according to a new study from the University of Georgia.

And most are using a wider range of communication tools to stay in touch.

Study author Kerstin Emerson, a clinical associate professor of gerontology at UGA's Institute of Gerontology, said she's concerned that older adults could be experiencing more exacerbated feelings of loneliness due to social distancing.

"Many of the social venues that help older adults stay engaged are effectively cut off now with social distancing. While the internet can help with some connections, it is hard to replace human contact," said Emerson. "And for some these remote connections aren't possible due to no reliable internet."

Once states began issuing shelter-in-place orders, Emerson decided to conduct of survey of U.S. older adults to get an idea of how they were coping and some possible ways to help.

A total of 833 adults aged 60 and older living in the U.S. completed the survey between March 30 and April 12.

The Centers for Disease Control and Prevention released recommendations on March 5 encouraging older adults to stay home to protect themselves from COVID-19 exposure. By the time participants took the survey, they had been social distancing for an average of 17 days.

She was especially interested in how the responses differed among two subsets of survey participants - those aged 60 to 70 and adults 71 and older.

"Part of the reason I did that was because I wanted to see if there was a difference by age groups, among the 'younger old' and 'older old,' who may have different work responsibilities and living situations," said Emerson.

Two themes emerged from survey responses, which seemed to break down along that age line. About 40% of 60- to 70-year-old respondents said they felt moderately or very stressed and felt out of control of their lives.

That could be why Emerson found that this subgroup reported more increases in some unhealthy behaviors, such as drinking more alcohol and eating more than usual. One-third report exercising less. Although Emerson also notes that one-third of the same group are exercising more.

But the older subgroup, those 71 and older, seem to be handling stress better than their younger counterparts - 74% said that they were experiencing little to no stress, comparing the current situation to being no more stressful than living through past war times.

"That's where older adults have a strength," said Emerson. "They have life experience and coping mechanisms that we don't often give them credit for, but that's part of their wisdom. We can really turn to older adults as examples of how to manage and live through bad periods of history."

Unsurprisingly, communication across all modes has increased. More older adults are calling, texting, emailing and perusing social media.

Notably, compared to pre-social distancing, two-thirds of respondents are on social media, like Facebook, and using more smart devices. Over half reported using video calls once a day.

This information is key for public health practitioners, said Emerson, who are trying to craft interventions to support the emotional and physical well-being of older adults remotely.

Emerson noted that the survey respondents represent individuals who have access to the internet and a personal computer or smart device, "so we're probably not reaching the most vulnerable populations, people who are socially isolated in rural areas or who are incredibly poor."

There is always more to learn, said Emerson.

"The survey ends up raising more questions than giving answers in some cases, but that's the nature of it."

AMES, Iowa - Say there's a bomb attack on a military base. A few of the soldiers suffer concussions and other brain injuries. Could some of the injuries be caused by tiny bubbles that form and collapse within the skull during head trauma?

Researchers at Iowa State University, with the support of grants from the Office of Naval Research, are using their expertise with the manufacture of microstructures to study and describe the damage to brain cells caused by the formation and collapse of microbubbles - a process known as cavitation.

The researchers report their findings in a paper featured on the cover of the July 2020 issue of the research journal Global Challenges. Lead authors are Nicole Hashemi, an Iowa State associate professor of mechanical engineering, and Alex Wrede, a former doctoral student and postdoctoral research associate in Hashemi's lab. (See sidebar for the other co-authors.)

The researchers write that microbubbles measured in microns - that's millionths of a meter - can form in cerebral spinal fluid inside the skull during traumatic brain injuries.

The researchers wrote the "formation and dramatic collapse" of these microbubbles could be responsible for some of the damage in a brain injury.

Bubble damage may sound trivial. But bubble collapse, and the resulting shock waves, are known to damage the steel foundations of boat propellers. The researchers report that prior studies indicate the expansion and collapse of microbubbles creates forces of 0.1 to 20 megapascals, or 14.5 to 2,900 pounds per square inch.

" ... So it is alarming to realize the damage that cavitation inflicts on vulnerable brain tissue," the researchers wrote.

Looking for changes in brain cells

To test and characterize the impact of cavitation inside the skull, the researchers simulated a brain by creating a 3D cell culture platform for astrocytic cells (star-shaped cells in the brain and spinal cord that are active in supporting, maintaining and repairing the central nervous system). They submerged the cell culture platform in a small tank and created microbubbles around 60 millionths of a meter in size. Some of the microbubbles adhered to the cell-laden microfiber scaffold.

Researchers turned on an ultrasonic device in the tank, collapsing the microbubbles and creating cavitation. (They also used the ultrasonic device on a control group of cells that were not exposed to cavitation.)

The researchers looked for two kinds of effects:

First, they used an inverted microscope to record any morphological changes to the cells. Second, they worked with colleagues in Iowa State's College of Veterinary Medicine to assess whether there were genetic changes in the cells.

The researchers found cavitation caused the cells to shrink and roughened their surfaces. The cells appeared to elongate and grow when images were taken 22 and 48 hours after cavitation. Even so, the researchers found cell growth after 48 hours- in terms of surface area - was about half as much as the control cells.

The researchers also found the cells damaged by cavitation had elevated expression of genes
such as TNF-α and IL-6, which are associated with inflammatory conditions such as infection with the SARS-CoV-2 virus and neurological disorders such as Parkinson's and Alzheimer's diseases.

"Taken together, these results confirm that surrounding cavitation is detrimental to astrocytic function," the researchers wrote.

Designing better helmets

Hashemi said while doctors look for treatments for the brain damage caused by cavitation, she said engineers can work to identify the places in the brain where cavitation is most likely to occur.

"A location map of cavitation occurrence can be directly used to design a helmet that dampens force and reduces the possibility of cavitation," the researchers wrote.

And while this study focusses on military helmets, Hashemi said the same ideas could be applied to helmets for football and other sports.

"This research is looking at battlefield applications, but in football there are similar impacts and shock waves," Hashemi said. "Players do get mild forms of traumatic brain injury. Players might not realize it, but the effects of cavitation injuries would be there."

Wrede, Hashemi's former graduate student who's now working as a dynamic systems modeling engineer for John Deere in Dubuque, said the project has taught him there's great need for more research and development.

"The people who have served our country and come back with injuries are really relying on research to find answers," he said. "Answers could improve quality of life for our veterans and everybody unfortunate enough to go through traumatic brain injury."

An international team led by researchers at Princeton University has uncovered a new class of magnet that exhibits novel quantum effects that extend to room temperature.

The researchers discovered a quantized topological phase in a pristine magnet. Their findings provide insights into a 30-year-old theory of how electrons spontaneously quantize and demonstrate a proof-of-principle method to discover new topological magnets. Quantum magnets are promising platforms for dissipationless current, high storage capacity and future green technologies. The study was published in the journal Nature this week.

The discovery's roots lie in the workings of the quantum Hall effect- a form of topological effect which was the subject of the Nobel Prize in Physics in 1985. This was the first time that a branch of theoretical mathematics, called topology, would start to fundamentally change how we describe and classify matter that makes up the world around us. Ever since, topological phases have been intensely studied in science and engineering. Many new classes of quantum materials with topological electronic structures have been found, including topological insulators and Weyl semimetals. However, while some of the most exciting theoretical ideas require magnetism, most materials explored have been nonmagnetic and show no quantization, leaving many tantalizing possibilities unfulfilled.

"The discovery of a magnetic topological material with quantized behavior is a major step forward that could unlock new horizons in harnessing quantum topology for future fundamental physics and next-generation device research" said M. Zahid Hasan, the Eugene Higgins Professor of Physics at Princeton University, who led the research team.

While experimental discoveries were rapidly being made, theoretical physics excelled at developing ideas leading to new measurements. Important theoretical concepts on 2D topological insulators were put forward in 1988 by F. Duncan Haldane, the Thomas D. Jones Professor of Mathematical Physics and the Sherman Fairchild University Professor of Physics at Princeton, who in 2016 was awarded the Nobel Prize in Physics for theoretical discoveries of topological phase transitions and topological phases of matter. Subsequent theoretical developments showed that topological insulator-hosting magnetism in a special atomic arrangement known as a kagome lattice can host some of the most bizarre quantum effects.

Hasan and his team has been on a decade-long search for a topological magnetic quantum state that may also operate at room temperature since their discovery of the first examples of three dimensional topological insulators. Recently, they found a materials solution to Haldane's conjecture in a kagome lattice magnet that is capable of operating at room temperature, which also exhibits the much desired quantization. "The kagome lattice can be designed to possess relativistic band crossings and strong electron-electron interactions. Both are essential for novel magnetism. Therefore, we realized that kagome magnets are a promising system in which to search for topological magnet phases as they are like the topological insulators that we studied before," said Hasan.

For so long, direct material and experimental visualization of this phenomenon has remained elusive. The team found that most of the kagome magnets were too difficult to synthesize, the magnetism was not sufficiently well understood, no decisive experimental signatures of the topology or quantization could be observed, or they operate only at very low temperatures.

"A suitable atomic chemistry and magnetic structure design coupled to first-principles theory is the crucial step to make Duncan Haldane's speculative prediction realistic in a high-temperature setting," said Hasan. "There are hundreds of kagome magnets, and we need both intuition, experience, materials-specific calculations, and intense experimental efforts to eventually find the right material for in-depth exploration. And that took us on a decade-long journey."

Through several years of intense research on several families of topological magnets (Nature 562, 91 (2018); Nature Phys 15, 443 (2019), Phys. Rev. Lett. 123, 196604 (2019), Nature Commun. 11, 559 (2020), Phys. Rev. Lett. 125, 046401 (2020)), the team gradually realized that a material made of the elements terbium, magnesium and tin (TbMn6Sn6) has the ideal crystal structure with chemically pristine, quantum mechanical properties and spatially segregated kagome lattice layers. Moreover, it uniquely features a strong out-of-plane magnetization. With this ideal kagome magnet successfully synthesized at the large single crystal level by collaborators from Shuang Jia's group at Peking University, Hasan's group began systematic state-of-the-art measurements to check whether the crystals are topological and, more important, feature the desired exotic quantum magnetic state.

The Princeton team of researchers used an advanced technique known as scanning tunneling microscopy, which is capable of probing the electronic and spin wavefunctions of a material at the sub-atomic scale with sub-millivolt energy resolution. Under these fine-tuned conditions, the researchers identified the magnetic kagome lattice atoms in the crystal, findings that were further confirmed by state-of-the-art angle-resolved photoemission spectroscopy with momentum resolution.

"The first surprise was that the magnetic kagome lattice in this material is super clean in our scanning tunneling microscopy," said Songtian Sonia Zhang, a co-author of the study who earned her Ph.D. at Princeton earlier this year. "The experimental visualization of such a defect-free magnetic kagome lattice offers an unprecedented opportunity to explore its intrinsic topological quantum properties."

The real magical moment was when the researchers turned on a magnetic field. They found that the electronic states of the kagome lattice modulate dramatically, forming quantized energy levels in a way that is consistent with Dirac topology. By gradually raising the magnetic field to 9 Tesla, which is hundreds of thousands of times higher than the earth's magnetic field, they systematically mapped out the complete quantization of this magnet. "It is extremely rare -- there has not been one found yet -- to find a topological magnetic system featuring the quantized diagram. It requires a nearly defect-free magnetic material design, fine-tuned theory and cutting-edge spectroscopic measurements" said Nana Shumiya, a graduate student and co-author of the study.

The quantized diagram that the team measured provides precise information revealing that the electronic phase matches a variant of the Haldane model. It confirms that the crystal features a spin-polarized Dirac dispersion with a large Chern gap, as expected by the theory for topological magnets. However, one piece of the puzzle was still missing. "If this is truly a Chern gap, then based on the fundamental topological bulk-boundary principle, we should observe chiral (one-way traffic) states at the edge of the crystal," Hasan said.

The final piece fell into place when the researchers scanned the boundary or the edge of the magnet. They found a clear signature of an edge state only within the Chern energy gap. Propagating along the side of the crystal without apparent scattering (which reveals its dissipationless character), the state was confirmed to be the chiral topological edge state. Imaging of this state was unprecedented in any previous study of topological magnets.

The researchers further used other tools to check and reconfirm their findings of the Chern gapped Dirac fermions, including electrical transport measurements of anomalous Hall scaling, angle-resolved photoemission spectroscopy of the Dirac dispersion in momentum space, and first-principles calculations of the topological order in the material family. The data provided a complete spectrum of inter-linked evidence all pointing to the realization of a quantum-limit Chern phase in this kagome magnet. "All the pieces fit together into a textbook demonstration of the physics of Chern-gapped magnetic Dirac fermions," said Tyler A. Cochran, a graduate student and co-first author of the study.

Now the theoretical and experimental focus of the group is shifting to the dozens of compounds with similar structures to TbMn6Sn6 that host kagome lattices with a variety of magnetic structures, each with its individual quantum topology. "Our experimental visualization of the quantum limit Chern phase demonstrates a proof-of-principle methodology to discover new topological magnets," said Jia-Xin Yin, a senior postdoctoral researcher and another co-first author of the study.

"This is like discovering water in an exoplanet - it opens up a new frontier of topological quantum matter research our laboratory at Princeton has been optimized for," Hasan said.