Culture

In a new study published in Cell Stem Cell, a team led by USC Stem Cell scientist Michael Bonaguidi, PhD, demonstrates that neural stem cells - the stem cells of the nervous system - age rapidly.

"There is chronological aging, and there is biological aging, and they are not the same thing," said Bonaguidi, an Assistant Professor of Stem Cell Biology and Regenerative Medicine, Gerontology and Biomedical Engineering at the Keck School of Medicine of USC. "We're interested in the biological aging of neural stem cells, which are particularly vulnerable to the ravages of time. This has implications for the normal cognitive decline that most of us experience as we grow older, as well as for dementia, Alzheimer's disease, epilepsy and brain injury."

In the study, first author Albina Ibrayeva, a PhD candidate in the Bonaguidi Lab in the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, joined her colleagues in looking at the brains of young, middle-aged and old mice.

By tracing individual neural stem cells, or NSCs, over the course of several months, they identified "short-term NSCs" that quickly differentiate into more specialized neurons, and "long-term NSCs" that continually divide and replicate themselves to maintain an ongoing reserve of stem cells with the ability to generate many different cell types in the brain. This key population of long-term NSCs divided less often and failed to maintain their numbers as the mice aged.

The scientists next examined thousands of genes in the long-term NSCs, which were dividing less often and had slipped into an inactive state known as quiescence. The gene activity of the quiescent NSCs varied greatly in young versus middle-aged animals. As expected, there were changes in genes that control how long-term NSCs divide, as well as generate new neurons and other brain cells. Remarkably, there were many important changes in gene activity related to biological aging at younger ages than anticipated. These pro-aging genes make it more difficult for cells to repair damage to their DNA, regulate their genetic activity, control inflammation and handle other stresses.

Among the pro-aging genes, the scientists were most intrigued by Abl1, which formed the hub of a network of interrelated genes.

"We were interested in the gene Abl1, because no one has ever studied its role in neural stem cell biology--whether in development or in aging," said Ibrayeva.

Using an existing, FDA-approved chemotherapy drug called Imatinib, scientists could easily inhibit the activity of the gene Abl1. The scientists gave older mice doses of Imatinib for six days. After the drug blocked the activity of the gene Abl1, the NSCs began to divide more and proliferate in the hippocampus, the part of the brain responsible for learning and memory.

"We've succeeded in getting neural stem cells to divide more without depleting, and that's step one," said Bonaguidi. "Step two will be to induce these stem cells to make more neurons. Step three will be to demonstrate that these additional neurons actually improve learning and memory. Much work remains to be done, but this study marks exciting progress towards our goal of identifying prescription drugs that could rejuvenate our brains as we grow older."

Young scientists from NUST MISIS have presented multilayer antibacterial coatings with a prolonged effect and a universal spectrum of action. The coating is based on modified titanium oxide and several antiseptic components. The coatings can be used in modern implantology as a protective layer for the prevention of concomitant complications - inflammation or implant rejection. The results of the work have been published in the international scientific journal Applied Surface Science.

Antibacterial coatings are currently being actively researched, as the search for alternatives to traditional antibiotics is growing. They can be applied to implants, thereby preventing inflammation caused by nosocomial infections.

Nevertheless, the creation of antibacterial, but at the same time biocompatible and bioactive surfaces is a problem that the scientific community has been solving for many years, and the "dream materials" have not been developed.

Young scientists from the NUST MISIS Laboratory of Inorganic Nanomaterials have created an innovative multilayer coating that synthesizes the protective properties of nanoparticles, biopolymers, anticoagulants and antibiotics. The antibiotic and silver nanoparticles provide an antibacterial effect, while heparin prevents bacterial cells from sticking to the tissue surface, which reduces the amount of antibacterial agent required.

"The method of obtaining a multilayer coating is a combination of several technologies: first, using magnetron sputtering, a thin bioactive nanostructured coating of the TiCaPCON composition was obtained, then silver particles were introduced into the coating by ion implantation, then a biopolymer layer, which plays the role of a carrier for bactericidal molecules of heparin and gentamicin in the preparation, was applied", - said the author of the work, a researcher at the NUST MISIS Inorganic nanomaterials laboratory Elizaveta Permyakova.

The chemical composition of the resulting coating layers was carefully studied by the developers using infrared and X-ray photoelectron spectroscopy. Scientists have found out that the incorporation of therapeutic components occurs throughout the whole plasma-applied polymer layer.

Together with colleagues from the State Research Center for Applied Microbiology and Biotechnology, the scientists studied the effect of each type of the antibacterial component (silver ions, gentamicin and heparin) on the antibacterial activity and biocompatibility of the obtained coatings.

According to the results of in vitro studies, the coatings showed cellular compatibility and demonstrated excellent (up to 99%) bactericidal efficacy against the antibiotic-resistant E. coli bacterial strain.

"The combination of several bactericidal fillers and silver ions with a bioactive coating made of titanium oxide modified with calcium and phosphorus ensured biocompatibility and a long - up to 7 days - antibacterial effect of the resulting coatings," emphasized Elizaveta Permyakova.

According to the developers, the innovative coatings can be used as an antibacterial implant modifier, allowing it to accelerate implantation by reducing the risks of associated inflammation and stimulating the growth of osteoblastic cells.

Researchers are currently planning to move to the preclinical development stage.

DES PLAINES, IL - At the beginning of prioritized health care personnel (HPC) immunization, there was a high rate of COVID-19 vaccine acceptance and receipt, with physicians and advance practice providers having the highest overall proportion. These are the findings of a surveillance project on COVID-19 vaccination rates among emergency department staff at United States academic medical centers, which will be published in the April issue of the Academic Emergency Medicine (AEM) journal, a peer-reviewed journal of the Society for Academic Emergency Medicine (SAEM).

The project report, published in a research letter titled Vaccination rates and acceptance of SARS-CoV-2 vaccination among U.S. emergency department health care personnel, also found that a substantial percentage of emergency department HPCs declined vaccination, primarily due to concerns over safety. Because of this, the authors suggest that efforts at educating HCPs about the safety profile of COVID-19 vaccines may be warranted, especially in groups that had the most vaccine (i.e., nonclinical, nursing, and Black HCPs).

The lead author of the report is Walter A. Schrading, MD, of the department of emergency medicine at the University of Alabama, Birmingham in Birmingham, Alabama. The project findings are discussed with Dr. Schrading in a recent AEM Early Access podcast.

Commenting on the study is Elizabeth Goldberg, MD, an associate professor of emergency medicine and health services, policy & practice at Brown University. Her research focuses on improving emergency care for older adults and she is the cofounder of MyCovidRisk.app, a web-based tool to help individuals estimate their COVID-19 risk and reduce their risk of SARS-CoV-2 transmission.

"This study by Schrading and Trent et al. demonstrates that emergency department physicians and advance practice providers almost never declined COVID-19 vaccination (

A team led by University of Minnesota researchers has discovered that deep-sea bacteria dissolve carbon-containing rocks, releasing excess carbon into the ocean and atmosphere. The findings will allow scientists to better estimate the amount of carbon dioxide in Earth's atmosphere, a main driver of global warming.

The study is published in The ISME Journal: Multidisciplinary Journal of Microbial Ecology, a peer-reviewed scientific journal that is part of the Nature family of publications and the official journal of the International Society for Microbial Ecology (ISME).

"If CO2 is being released into the ocean, it's also being released into the atmosphere, because they're constantly interchanging gases between them," explained Dalton Leprich, the first author on the paper and a Ph.D. student in the University of Minnesota's Department of Earth and Environmental Sciences. "While it's not as big of an impact as what humans are doing to the environment, it is a flux of CO2 into the atmosphere that we didn't know about. These numbers should help us home in on that global carbon budget."

The researchers began studying sulfur-oxidizing bacteria--a group of microbes that use sulfur as an energy source--in methane seeps on the ocean floor. Akin to deep-sea coral reefs, these "seeps" contain collections of limestone that trap large amounts of carbon. The sulfur-oxidizing microbes live on top of these rocks.

After noticing patterns of corrosion and holes in the limestone, the researchers found that in the process of oxidizing sulfur, the bacteria create an acidic reaction that dissolves the rocks. This then releases the carbon that was trapped inside the limestone.

"You can think of this like getting cavities on your teeth," Leprich said. "Your tooth is a mineral. There are bacteria that live on your teeth, and your dentist will typically tell you that sugars are bad for your teeth. Microbes are taking those sugars and fermenting them, and that fermentation process is creating acid, and that will dissolve away at your teeth. It's a similar process to what's happening with these rocks."

The researchers plan to test out this effect on different mineral types. In the future, these findings could also help scientists use dissolution features--holes, crevices, or other evidence that rocks have been dissolved by bacteria--to discover evidence of life on other planets, such as Mars.

"These findings are but one of the many examples of the important and understudied role that microbes play in mediating the cycling of elements on our planet," said Jake Bailey, a University of Minnesota Department of Earth and Environmental Sciences associate professor and corresponding author of the study.

Cows don't seem to have a whole lot going on most of the time. They're raised to spend their days grazing in the field, raised for the purpose of providing milk or meat, or producing more cows. So when students in UC Santa Barbara ecologist Doug McCauley's lab found themselves staring intently at satellite image upon image of bovine herds at Point Reyes National Seashore, it was funny, in a "Far Side" kind of way.

"There were about 10 undergrads involved in the project, spotting cows from space -- not your typical student research and always amusing to see in the lab," McCauley said. They became proficient at discerning the top view of a cow from the top view of rocks or the top view of other animals, he added.

"After about eight months, we ended up with more than 27,000 annotations of cattle across 31 images," said Lacey Hughey, an ecologist with the Smithsonian Conservation Biology Institute who was a Ph.D. student in the McCauley Lab at the time, and the leader of the cow census. "It took a long time."

All of the rather comical cow counting had a serious purpose, though: to measure the interactions between wildlife and livestock where their ranges meet or overlap. Roughly a third of the United States' land cover is rangeland, and where these grazing areas abut wildland, concerns over predation, competition and disease transmission are bound to arise.

Such is the case at Point Reyes National Seashore, a picturesque combination of coastal bluffs and pastureland about an hour's drive north of San Francisco. As part of a statewide species restoration plan, native tule elk were reintroduced to the park's designated wilderness area in the 1990s, but they didn't stay in their little corner of paradise for very long.

"Some of them actually ended up swimming across an estero and establishing this herd -- which is known as the Drake's Beach Herd -- near the pastoral zone of the park, which is leased to cattle ranchers," said Hughey, the lead author of a collaborative study with the University of Nevada, Reno, that appears in the journal Biological Conservation. Cattle fences don't stop elk either, she said; they can easily cross or break through them to enter pastures. The situation was also somewhat unique in that the Drake's Beach elk live in the area year-round, thanks in large part to the stable climate, so grazing pressure on the land is constant.

Where's the beef?

"So we were wondering, how do elk and cattle co-exist in this landscape?" Hughey said. "The story between elk and cattle is actually pretty complex. We know from other studies that elk and cattle can be competitors, but they can also be facilitators. We also didn't know very much about which habitats elk preferred in this part of the park and how the presence of cattle might influence an elk's decision to spend its time in one place over another."

The researchers set out to answer these questions with two large datasets generated by the park -- GPS monitoring data from collared elk, and field-based transect surveys of the elk. What was missing, however, was information on the cows.

"We knew quite a bit about where the elk were, but we didn't have any information about where the cows were, except that they were inside the fences," she said. Knowing the precise number and location of cows relative to the elk herd would be necessary to understand how both species interact in a pastoral setting.

"Because the elk data was collected in the past, we needed a way to obtain information on cattle populations from the same time period. The only place we could get that was from archived, high-resolution satellite imagery," Hughey said. Hence, the satellite cowspotting.

Their conclusion? Elk have acclimated to cattle at Point Reyes by avoiding cow pastures in general and by choosing separate foraging sites on the occassions that they co-occur. Taken together, these findings suggest that elk select habitat in a manner "that reduce[s] the potential for grazing conflicts with cattle, even in cases where access to forage is limited."

In addition to helping shed light on the ecological relationship between cows and tule elk at Point Reyes, satellite imaging can also define their areas of overlap -- an important consideration in the assessment of disease risk, the researchers said.

"There's a disease of concern that's been found in the elk herd and also in the cattle, called Johne's disease," Hughey said. The bacteria that cause it can persist in the environment for more than a year, she added, so even though cows and elk rarely share space at the same time, there is still a theoretical risk of transmission in this system.

Sharing space

According to the researchers, the satellite imaging technique is also widely applicable to other areas on the globe where livestock and wildlife ranges overlap.

"The issue of livestock and wildlife being in conflict is a major challenge in a bunch of different contexts in the U.S. and beyond," McCauley said. "It has been surprisingly hard to figure out exactly how these wild animals share space with domestic animals."

These new methods, he said, "will have a transformative impact on understanding how livestock use wildlands -- and how wildlife use grazing lands."

Next stop: Kenya and Tanzania.

Working with the National Geospatial Intelligence Agency, Microsoft AI for Good, University of Glasgow, and University of Twente -- and thanks in large part to the data generated by those cow-tracking UC Santa Barbara undergrads -- Hughey and colleagues are training an algorithm to detect and identify animals in the plains of East Africa, such as wildebeest and, of course, cows.

When Iranian authorities started seizing Barbie dolls from Tehran toy shops in 2012, Mattel Inc. execs faced concerns not only about the dolls' attire -- miniskirts and swimsuits considered immodest in an Islamic country -- but also questions from the U.S. Securities and Exchange Commission (SEC) about Mattel's ties to Iran.

U.S. businesses are restricted from business in Iran, which U.S. authorities have designated a state sponsor of terrorism (SST). The number of SEC inquiries about potential terrorist ties has grown substantially in recent years, and according to new research from Duke University's Fuqua School of Business, the increase could reduce the quality of the agency's financial reporting oversight.

"Comments on terrorism are getting to a critical level of importance in terms of what the SEC is asking companies about," said Bill Mayew, a Fuqua accounting professor and co-author of research, which is forthcoming in the Journal of Accounting & Economics. "Investors want to be aware if the companies they invest in are potentially supporting terrorism, but they also want financial statements that are correct. The SEC has to balance both of these issues to protect investors."

TRACKING FOCUS AREAS AT THE SEC

Mayew, along with Fuqua Ph.D. alumni Robert Hills of Penn State and Matthew Kubic of the University of Texas at Austin, analyzed the more than 17,800 comment letters from SEC review staff from 2005 to 2016. Comment letters are typically sent after SEC staff reviews a firm's disclosures to gather more information or notify a firm that its filings contain inaccuracies or errors.

Of the 825 comment letters the SEC sent in 2005, only 2.2% included comments related to SST, the analysis showed. By 2016, that number had grown to 8.4%. Terrorism has become as commonplace a topic in comment letters as questions about financial information such as intangible assets, revenue recognition and taxes, Mayew said.

The researchers found that when SEC comment letters included references to terrorism, the letters were less likely to identify the firm's financial reporting errors.

To determine cases in which errors were caught and missed, researchers analyzed comment letters as well as subsequent corrections, or restatements, from the firms that received comment letters.

Among restatements that investors typically care most about - those containing severe errors - the SECs' average error-detection rate was 31.1%, the data showed. The error-detection rate dropped to 10.6% when letters included the topic of terrorism disclosures, the researchers found.

"The inference from our paper is that when the focus turns to terrorism it appears to come at the expense of financial reporting oversight," Mayew said.

The SEC bases some of its terrorism-related inquiries on contents in financial filings, but may also proactively review sources such as the news and websites for the company and its affiliates for information about firms' possible ties to countries on the U.S. Department of State's SST list, which also includes Cuba, North Korea and Syria.

During the same year news coverage piqued the SEC's interest in Mattel, the SEC also contacted Heinz after reports suggested its ketchup was available in both Cuba and Syria. After financial disclosures, news coverage was the most common source the SEC referenced in its questions about SST issues, the research showed.

AN INFLUX OF LAWYERS

The SEC's attention to firms' financial ties to SST countries began at Congress's behest in 2003 after incidents such as the 2001 World Trade Center attacks spurred new counter-terrorism efforts, Mayew said.

The researchers found that this coincided with a shift in the composition of SEC review staff -- the number of lawyers the review staff has grown while the number of accountants has decreased, the researchers found. Data showed accountants were more likely to ask accounting questions and detect errors in financial statements while lawyers were more likely to ask questions about terrorism-related activities, which limited the likelihood that the review detected errors.

The data also showed when SEC reviewers asked firms about potential ties to SST, the reviewers were less likely to ask a question regarding core financial reporting, which included topics like accounting policies, disclosures related to a firm's narrative explanation about its financial statements (known as MD&A disclosures), or non-GAAP metrics (metrics that fall outside of those reported under Generally Accepted Accounting Principles).

"Core financial reporting topics are known to be associated with financial misreporting," Mayew said. "Interest in SST crowds out inquiries on core financial reporting topics, likely underpinning why SST questions appear to inhibit the SEC's ability to detect financial misreporting."

SHOULD THE SEC REVIEW MORE OR LESS?

Experts inside and outside of the agency have questioned whether the SEC is sufficiently suited to regulate SST disclosure. As long ago as 2008, the Securities Industry and Financial Markets Association publicly opposed the SEC's activities, involvement in what the professional organization called matters of national security. Even a former SEC chair spoke publicly on the importance of the SEC's independence from political persuasion, and that the commission has, at times, been pushed into areas that may not fall within its core mission.

More recently, the SEC has also been called upon to facilitate accountability on how firms address environmental, social, and governance (ESG) factors, and other social issues, such as diversity, equity and inclusion. One such call to action was recently authored by faculty at Duke Law's Global Financial Markets Center, calling on the SEC to integrate ESG disclosures across a number of areas.

"As the SEC considers regulating disclosure in other domains such as ESG, our research demonstrates that careful thought must be placed into how the commission changes its staffing and how that could spill over to other areas like financial reporting," Mayew said. "If you now start making SEC staff members review whether financial filings adequately capture climate change risk or racism, for example, it may be headed down the same path as it has with investigating ties to terrorism."

Toronto (April 12, 2021) - Researchers from University Health Network have developed and validated an innovative deep learning model to predict a patient's long-term outcome after receiving a liver transplant.

First of its kind in the field of Transplantation, this model is the result from a collaboration between the Ajmera Transplant Centre and Peter Munk Cardiac Centre. The study, published in Lancet Digital Health, shows it can significantly improve long-term survival and quality of life for liver transplant recipients.

"Historically, we have seen good advances in one-year post-transplant outcomes, but survival in the longer term hasn't significantly improved in the past decades," explains Dr. Mamatha Bhat, a hepatologist with the Ajmera Transplant Centre at UHN and co-senior author of the study.

"This model can guide physicians and help anticipate when and how complications may rise. It can really be paradigm-changing in how we support liver transplant recipients in personalizing their care and helping them live better and longer."

For liver transplant recipients, long-term survival beyond one-year is significantly compromised by an increased risk of cancer, cardiovascular mortality, infection and graft failure. Clinical tools to identify patients at risk of these complications are limited.

This model will help clinicians enhance post-liver transplant care using machine learning, allowing them to identify potential risks when formulating patient-specific treatment plans.

The study results show this model is more than 80% accurate in predicting potential complications for liver transplant recipients at any point post- transplantation, based on their medical history and comparing to the millions of data points compiled using artificial intelligence.

"Deep Learning enables timely processing of large-scale datasets, finding patterns and signals that can aid clinicians in better predicting the clinical outcomes and creating specific treatment recommendations," says Dr. Bo Wang, AI Lead at the Peter Munk Cardiac Centre, CIFAR AI Chair at the Vector Institute and co-senior author of this study.

The algorithms for this model were created based on the Scientific Registry of Transplant Recipients (SRTR) - a national medical database in the United States, with data from over 42,000 liver transplant recipients. They were then validated using the local dataset from UHN's Ajmera Transplant Centre, which had over 3,200 cases.

The research team now plans to share this model with clinicians so that it can be used across the world. Work is also in progress to evaluate what are the best formats to streamline its use, either developing a software or mobile application.

WASHINGTON, April 12, 2021 -- Spiders are master builders, expertly weaving strands of silk into intricate 3D webs that serve as the spider's home and hunting ground. If humans could enter the spider's world, they could learn about web construction, arachnid behavior and more. Today, scientists report that they have translated the structure of a web into music, which could have applications ranging from better 3D printers to cross-species communication and otherworldly musical compositions.

The researchers will present their results today at the spring meeting of the American Chemical Society (ACS). ACS Spring 2021 is being held online April 5-30. Live sessions will be hosted April 5-16, and on-demand and networking content will continue through April 30. The meeting features nearly 9,000 presentations on a wide range of science topics.

"The spider lives in an environment of vibrating strings," says Markus Buehler, Ph.D., the project's principal investigator, who is presenting the work. "They don't see very well, so they sense their world through vibrations, which have different frequencies." Such vibrations occur, for example, when the spider stretches a silk strand during construction, or when the wind or a trapped fly moves the web.

Buehler, who has long been interested in music, wondered if he could extract rhythms and melodies of non-human origin from natural materials, such as spider webs. "Webs could be a new source for musical inspiration that is very different from the usual human experience," he says. In addition, by experiencing a web through hearing as well as vision, Buehler and colleagues at the Massachusetts Institute of Technology (MIT), together with collaborator Tomás Saraceno at Studio Tomás Saraceno, hoped to gain new insights into the 3D architecture and construction of webs.

With these goals in mind, the researchers scanned a natural spider web with a laser to capture 2D cross-sections and then used computer algorithms to reconstruct the web's 3D network. The team assigned different frequencies of sound to strands of the web, creating "notes" that they combined in patterns based on the web's 3D structure to generate melodies. The researchers then created a harp-like instrument and played the spider web music in several live performances around the world.

The team also made a virtual reality setup that allowed people to visually and audibly "enter" the web. "The virtual reality environment is really intriguing because your ears are going to pick up structural features that you might see but not immediately recognize," Buehler says. "By hearing it and seeing it at the same time, you can really start to understand the environment the spider lives in."

To gain insights into how spiders build webs, the researchers scanned a web during the construction process, transforming each stage into music with different sounds. "The sounds our harp-like instrument makes change during the process, reflecting the way the spider builds the web," Buehler says. "So, we can explore the temporal sequence of how the web is being constructed in audible form." This step-by-step knowledge of how a spider builds a web could help in devising "spider-mimicking" 3D printers that build complex microelectronics. "The spider's way of 'printing' the web is remarkable because no support material is used, as is often needed in current 3D printing methods," he says.

In other experiments, the researchers explored how the sound of a web changes as it's exposed to different mechanical forces, such as stretching. "In the virtual reality environment, we can begin to pull the web apart, and when we do that, the tension of the strings and the sound they produce change. At some point, the strands break, and they make a snapping sound," Buehler says.

The team is also interested in learning how to communicate with spiders in their own language. They recorded web vibrations produced when spiders performed different activities, such as building a web, communicating with other spiders or sending courtship signals. Although the frequencies sounded similar to the human ear, a machine learning algorithm correctly classified the sounds into the different activities. "Now we're trying to generate synthetic signals to basically speak the language of the spider," Buehler says. "If we expose them to certain patterns of rhythms or vibrations, can we affect what they do, and can we begin to communicate with them? Those are really exciting ideas."

DALLAS, April 12, 2021 -- Testing how well "good" cholesterol particles reduce inflammation may help predict who is at heightened risk to develop cardiovascular disease caused by narrowed arteries, according to research published today in the American Heart Association's flagship journal Circulation.

Assessing levels of high-density lipoprotein (HDL) cholesterol, known as "good cholesterol," are already a standard part of formulas used to predict cardiovascular risk. A new test of the anti-inflammatory function of HDL seems to provide additional information that is independent of the quantity of HDL. If the results are confirmed in broader populations and a test developed for clinical use, adding anti-inflammatory capacity to risk scores may improve risk prediction and help people take steps to protect themselves against heart disease.

"HDL are very complex particles with anti-atherosclerotic functions that are not reflected by measuring just the cholesterol quantity," said senior study author Uwe J.F. Tietge, M.D., Ph.D., professor and head of the division of clinical chemistry at the Karolinska Institute in Stockholm, Sweden. "Atherosclerosis [plaque build-up in the arteries] underlying cardiovascular disease is increasingly recognized as a disease with a strong inflammatory component, and a central biological function of HDL is to decrease inflammation."

This study is the first to test whether better anti-inflammatory function of HDL particles protects against heart attacks and other serious heart-related events.

Participants included 680 white adults (average age of 59, 70% male) living in the Netherlands who were part of a large population study that began in 1997. All were healthy when they enrolled in the study. From the larger study participants were identified who'd had a first cardiovascular disease event before the end of the study follow-up. HDL particles were analyzed in 340 people who experienced a first fatal or non-fatal heart attack, were diagnosed with heart problems caused by narrowed heart arteries (ischemic heart disease) or who required a procedure to open clogged coronary arteries during the median 10.5-year follow-up period. These participants were matched to a control group of 340 people of the same age (within 5 years), sex, smoking status and HDL cholesterol levels who had no cardiovascular events during follow-up.

Several lab tests were performed for all participants at enrollment, including measuring the ability of isolated HDL particles to decrease the inflammatory response of endothelial cells lining blood vessels (called the anti-inflammatory capacity). Researchers also measured C-reactive protein, a substance that rises when there is more inflammation throughout the body, and cholesterol efflux capacity, a laboratory assessment of how efficiently HDL can remove cholesterol from cells that resemble those found in plaque.

The researchers found:

HDL anti-inflammatory capacity was significantly higher in people who remained healthy (31.6%) than in those who experienced a cardiovascular event (27%);

The association of anti-inflammatory capacity with cardiovascular events was independent of the established biomarkers of HDL cholesterol and C-reactive protein levels, and was also independent of cholesterol efflux capacity;

For every 22% increase in the ability of HDL particles to suppress inflammation in endothelial cells, participants were 23% less likely to have a cardiovascular event during the next decade;

The amount of protection from increased HDL anti-inflammatory capacity was higher in women than in men; and

Risk prediction was improved by adding HDL anti-inflammatory capacity to the Framingham Risk Score, or by replacing HDL cholesterol levels with this new measure of HDL function.

"By using a novel research tool, our results provide strong support for the concept that plaque buildup in the arteries has an inflammatory component, and that the biological properties of HDL particles have clinical relevance to cardiovascular disease risk prediction," said Tietge.

Although the results raise intriguing possibilities for improved screening, the results must be confirmed in different populations. In addition, a simpler and hopefully automated test for anti-inflammatory capacity should be developed first, researchers said.

"The HDL cholesterol level is a good, established, simple and cost-efficient CVD risk biomarker. Our results, however, demonstrate that the anti-inflammatory capacity or assays looking at HDL function in general have the potential to provide clinically relevant information beyond the static HDL cholesterol measurements that are currently used," Tietge said.

The findings also raise the possibility that medications to improve HDL anti-inflammatory capacity may be developed and used to lower heart disease risk.

Study limitations to be considered include that the study population was white and genetically similar, thus results are not generalizable to other race and ethnic groups. In addition, the researchers did not include stroke incidence in their analysis so conclusions cannot be drawn about HDL and stroke.

PULLMAN, Wash. - Humans cannot live on protein alone - even for the ancient indigenous people of the Pacific Northwest whose diet was once thought to be almost all salmon.

In a new paper led by Washington State University anthropologist Shannon Tushingham, researchers document the many dietary solutions ancient Pacific Coast people in North America likely employed to avoid "salmon starvation," a toxic and potentially fatal condition brought on by eating too much lean protein.

"Salmon was a critical resource for thousands of years throughout the Pacific Rim, but there were a lot of foods that were important," said Tushingham the lead author of the paper published online on April 8 in the American Journal of Physical Anthropology. "Native people were not just eating salmon. There's a bigger picture."

Some archeologists have contended for years that prehistoric Northwest people had an "extreme salmon specialization," a theory primarily based on the amount of salmon bone found at archeological sites.

Tushingham and her co-authors argue that such a protein-intensive diet would be unsustainable. They point to nutritional studies and a global database of hunter-gatherer diets that indicate people have dietary limit on lean protein of around 35%. While it can vary by individual, exceeding that ceiling can be physically debilitating within a few days and fatal within weeks. Early explorers in the U.S. West subsisting on lean wild game discovered this problem the hard way and called it "rabbit starvation" or "caribou sickness."

This toxic situation can apply to any lean meat, including salmon, Tushingham said. To avoid "salmon starvation", early Pacific Coast people had to find ways to get other nutrients, especially for children and nursing mothers who have even lower dietary thresholds for lean protein.

"There were ingenious nutritional and cultural solutions to the circumstances in the Northwest," said Tushingham. "Yes, salmon was important, but it wasn't that simple. It wasn't just a matter of going fishing and getting everything they needed. They also had to think about balancing their diet and making sure everybody could make it through the winter."

The researchers point to evidence in California that people offset stored salmon protein with acorns; in Oregon and Washington, they ate root crops like camas as well as more fat-heavy fish such as eulachon. Further north, where plants are more limited, communities often ate marine mammals with high fat content such as seals and walrus. In far north interior, where there are few plants and the salmon runs can go thousands of miles inland, this was particularly challenging. Lean dried salmon was an important food source, and people circumvented salmon starvation through trading for oil with coastal peoples or obtaining fat through processing bone marrow from caribou and elk.

The authors focus on the limits of salmon, which used to be considered a "prime mover" of Pacific Northwest populations, but their analysis also has implications for the study of historical human nutrition. If their argument is correct, it is unlikely that any human society was fully driven by pursuit of protein alone as their diets had to be more complex.

"People try to come up with one 'paleo-diet,' but there was no one specific ideal diet," said Tushingham. There were nutritional baselines that they had to cover, and nutritional limits that they couldn't exceed. There were many good solutions. It depended on where you lived and the history of your community."

Cranfield University research using data from smart meters has found that household water consumption changed significantly after the start of the COVID-19 lockdown, shifting from predominantly higher usage early in the morning to multiple peaks and continued demand throughout the day.

The study used machine learning algorithms to analyse and identify patterns in hourly water consumption data from 11,528 households in the East of England from January to May 2020.

The research is the first of its kind in the UK to quantify network consumption and segment households into different behavioural clusters according to significant differences in usage patterns.

Key findings were that:

There was an overall increase in household consumption from March to May 2020 compared to the same period in 2019, with the gap opening as lockdown restrictions deepened;

A sharp increase (10% on the previous week) in consumption was recorded in the fourth week of March - the week of the COVID-19 lockdown - rising to 46% above the pre-lockdown average in the fourth week of May;

Four distinct clusters of household water consumers can be characterised by their unique patterns of hourly use: early morning, late morning, evening peak and multiple peak;

The multiple peak cluster experienced the most significant increase in the number of households during the lockdown period, with a 93% rise between the third and fourth weeks of March;

The early morning cluster experienced the sharpest decrease in the number of households during the lockdown period, with a significant drop in their share of relative consumption between 07:00-08:00 a.m. from 40% to 20%.

Halidu Abu-Bakar, PhD researcher in the Cranfield Centre for Competitive Creative Design, Cranfield University, said: "The COVID-19 lockdown has instigated significant changes in household behaviour across a variety of categories including water consumption, which in the south and east regions of England is at an all-time high. The impact of the extended time people stayed at home under the lockdown and the ensuing changes in behaviour arising from this led to an increase in household water demand, exacerbating existing pressure on network water supply.

"Having knowledge of these patterns provides a solid framework for peak demand management and can help utility companies to forecast consumption, especially at unusual times such as pandemics, droughts and when there are seasonal variations."

Professor Leon Williams, Head of the Cranfield Centre for Competitive Creative Design, said: "Quality data driven research will provide the intelligence needed for water utilities to make strategic decisions."

Professor Stephen Hallett, Centre for Environmental and Agricultural Informatics, Cranfield University, said: "Water utility companies are increasingly searching for ways to understand the full nature of household water use, how to improve network demand forecasting and achieve effective water efficiency interventions. This data-driven characterisation of household clusters and understanding the impact of these unique patterns of behaviour on network demand can help in the design of demand forecasting and intervention that targets households on the basis of their shared cluster characteristics."

Research from Queen Mary University of London has revealed novel insights into the effects of chemotherapy on the tumour microenvironment (TME). The study, published today in Cancer Immunology Research, a journal of the American Association for Cancer Research, found that chemotherapy enhances the anti-tumour actions of immune cells within the TME and their ability to support immune responses against cancer.

Cancers are not just a mass of cancerous cells, but are rogue organs made up of many different cell types, including cells that form connective tissue and blood vessels, and immune cells. These non-cancerous cells have been recruited and corrupted by the cancer to help it grow and spread, and constitute what is known as the TME.

When treating cancer cells with chemotherapy, the cells within the TME are also impacted and previous research has shown that chemotherapy may activate immune cells within the TME to fight against the cancer. In this study, the team, led by Professor Fran Balkwill, investigated the effects of chemotherapy on immune cells called macrophages, which are associated with poor survival across a variety of cancer types. The study focused on high-grade serous ovarian cancer (HGSOC) - the most common type of ovarian cancer.

Chemotherapy switches immune cells to anti-tumour mode

By comparing biopsy samples taken from the omentum (most common site of cancer spread in HGSOC) of 26 patients prior to and after chemotherapy, the team found a significant reduction in the number of macrophages present in the tissues following treatment. Further investigations in samples from other HGSOC patients revealed that chemotherapy switched the remaining macrophages from a pro-tumour to an anti-tumour mode, which may stimulate the patient's immune response against the cancer.

The effects of chemotherapy on macrophages observed in patient samples were also seen in preclinical mouse models of HGSOC previously developed by the team, which recapitulate many aspects of the human omental TME.

As macrophages are associated with poor survival in cancer, the team took their research a step further to determine whether eliminating all macrophages from the TME after chemotherapy could prolong disease-free survival in the preclinical mouse models. To their surprise, removing all macrophages shortly after the completion of chemotherapy caused the mice to relapse quicker. Following three doses of chemotherapy, the macrophages had switched to an anti-tumour mode, and so eliminating the macrophages from the TME actually inhibited the immune response against the tumour and resulted in poorer survival outcomes.

The research was funded by Cancer Research UK, the Wellcome Trust and Wellbeing of Women.

Implications for ovarian cancer treatment

Chemotherapy and surgery are currently the main treatment options for patients with ovarian cancer. Despite chemotherapy working well initially, many patients experience relapse due to the development of resistance against these drugs.

Professor Balkwill from Queen Mary University of London said: "This study enhances our understanding of the impact of chemotherapy on macrophages and other aspects of the immune response. As our work was driven by results first obtained in patient samples and we were able to replicate the findings in our mouse models, we could investigate hypotheses and obtain data that have translational significance.

"We now have effective preclinical models of treatment and relapse that can be used to help identify treatments that build upon the tentative immune response triggered by chemotherapy."

Ultimately, the team hope that their models could help to identify new drug combinations that harness the initial immune-boosting effects of chemotherapy to reduce the number of required chemotherapy doses, minimise toxic side effects and improve survival for patients with ovarian cancer.

From power grids and telecommunications to water supply and financial systems, digital data controls the infrastructure systems on which society relies. These complex, multi-tier systems depend on layered communications to accomplish their tasks - yet every point of contact becomes a potential target, every path of information a potential weak spot for malicious actors to attack.

A team of researchers from the University of Calabria in Italy has developed the first predictive control scheme that can help distributed networks with multiple agents not only identify these attacks but also protect against them. Their approach was published in IEEE/CAA Journal of Automatica Sinica (Volume 8, Issue 3, March 2021).

"Modern systems have an increasing complex structure due to the large number of interacting agents aligned to accomplish specific tasks in a distributed fashion," said paper author Giuseppe Franzè, associate professor of control engineering in the Department of Informatics, Modeling, Electronics and System Engineering, University of Calabria. "The key result of the paper is that model predictive control strategies, properly adapted to multi-agent configurations, can address difficult scenarios such as the presence of intrusions such as replay attacks."

Replay attacks are difficult to identify because the malicious actor uses information already in the system. By stealing an account number or a permission string stolen from one transmission and using it on another agent - or even the agent who originally received the transmission - the actor can gain access or incite a specific action.

Franzè and his team applied a "receding horizon" model, that allows the researchers to predict what the system will look like in the future. By understanding what the system should look like, the model can identify when something unexpected occurs, like the resending of information.

"The receding horizon property allows us to consider the same structure of the optimization at each next time instant," Franzè said. "This means that if a problem is solvable at the initial time instant the same occurs in the future."

Importantly, according to Franzè, the strategy also offers protection by allowing the system to encapsulate in the moment before the attack, preserving communications until the attack can be successfully blocked.

"This low-demand model predictive control scheme is an efficient way to address unknown scenarios where external malicious agents affect normal system operations," Franzè said.

Osaka, Japan - Despite what some people think, bone is not merely a passive component of the body. The skeleton is structurally dynamic and responds to life's physical stresses with continual equilibration between bone mass loss and reformation. This ensures healing and remodeling in tune with the ebb and flow of calcium and phosphorus in the bloodstream. Now, researchers at Osaka university have identified a molecule—secretory leukocyte protease inhibitor (SLPI)—that helps mediate this critical balance, which could be used in the development of new treatments for bone diseases such as osteoporosis.

Skeletal tissue changes are orchestrated primarily by parathyroid hormone (PTH), a regulator of blood calcium levels that is secreted by the parathyroid glands in the neck. PTH is known to have a dual effect on bone—its action is primarily catabolic, causing bone dissolution and removal. However, in small intermittent doses, PTH can also increase bone mass (anabolic). Though PTH has long been used for the clinical treatment of osteoporosis, the precise mechanism and pathways whereby PTH promotes bone formation are poorly understood.

The researchers looked at the interactions between cells that mediate bone formation (osteoblasts), cells that mediate bone loss (osteoclasts) and the functional role of SLPI in bone metabolism in vivo. Akito Morimoto, lead author, explains the research methodology of the new study published in Nature Communications: "We could establish that PTH highly upregulates the gene Slpi in osteoblasts in animal models. We analyzed the bone phenotype of experimental mice in which the gene was 'knocked out' and showed that genetic modification of Slpi prevented PTH from inducing bone formation. Moreover, Slpi induction in osteoblasts themselves increased their differentiation while promoting osteoblast-osteoclast contact which reduces bone loss activity." Furthermore, biomicroscopic imaging in living bone demonstrated that SLPI secreted outside the cells is essential for association between osteoblasts and osteoclasts and the cell-cell interactions that PTH mediates.

Corresponding author Junichi Kikuta summarizes their results. "Our findings clarify the roles of SLPI as a novel coupling factor and coordinator of bone remodeling for conservation of mass, strength and structural integrity. Not only does it promote bone formation by osteoblasts, it also attracts osteoclasts closer to osteoblasts to suppress bone loss."

"A clear understanding of the cellular networks and molecular pathways that mediate PTH anabolism will enhance clinical applicability of this drug," senior author Masaru Ishii explains. "Moreover, it may inform the development of innovative pharmacotherapies for managing osteoporosis and other intractable orthopedic diseases."

Below the verdant surface and organic rich soil, life extends kilometers into Earth's deep rocky crust. The continental deep subsurface is likely one of the largest reservoirs of bacteria and archaea on Earth, many forming biofilms - like a microbial coating of the rock surface. This microbial population survives without light or oxygen and with minimal organic carbon sources, and can get energy by eating or respiring minerals. Distributed throughout the deep subsurface, these biofilms could represent 20-80% of the total bacterial and archaeal biomass in the continental subsurface according to the most recent estimate. But are these microbial populations spread evenly on rock surfaces, or do they prefer to colonize specific minerals in the rocks?

To answer this question, researchers from Northwestern University in Evanston, Illinois, led a study to analyze the growth and distribution of microbial communities in deep continental subsurface settings. This work shows that the host rock mineral composition drives biofilm distribution, producing "hotspots" of microbial life. The study was published in Frontiers in Microbiology.

Hotspots of microbial life

To realize this study, the researchers went 1.5 kilometers below the surface in the Deep Mine Microbial Observatory (DeMMO), housed within a former gold mine now known as the Sanford Underground Research Facility (SURF), located in Lead, South Dakota. There, below-ground, the researchers cultivated biofilms on native rocks rich in iron and sulfur-bearing minerals. After six months, the researchers analyzed the microbial composition and physical characteristics of newly grown biofilms, as well as its distributions using microscopy, spectroscopy and spatial modelling approaches.

The spatial analyses conducted by the researchers revealed hotspots where the biofilm was denser. These hotspots correlate with iron-rich mineral grains in the rocks, highlighting some mineral preferences for biofilm colonization. "Our results demonstrate the strong spatial dependence of biofilm colonization on minerals in rock surfaces. We think that this spatial dependence is due to microbes getting their energy from the minerals they colonize." explains Caitlin Casar, first author of the study.

Future research

Altogether, these results demonstrate that host rock mineralogy is a key driver of biofilm distribution, which could help improve estimates of the microbial distribution of the Earth's deep continental subsurface. But leading intraterrestrial studies could also inform other topics. "Our findings could inform the contribution of biofilms to global nutrient cycles, and also have astrobiological implications as these findings provide insight into biomass distributions in a Mars analog system" says Caitlin Casar.

Indeed, extraterrestrial life could exist in similar subsurface environments where the microorganisms are protected from both radiation and extreme temperatures. Mars, for example, has an iron and sulfur-rich composition similar to DeMMO's rock formations, which we now know are capable of driving the formation of microbial hotspots below-ground.