Tech

Stanford researchers find lead in turmeric

image: A merchant displays powdered and whole spices, including turmeric in the Karwan Bazar of Dhaka, Bangladesh.

Image: 
Abir Abdullah/Asian Development Bank

It's billed as a health booster and healing agent, but it may be the source of cognitive defects and other severe ailments. A new Stanford-led study reveals that turmeric - a commonly used spice throughout South Asia - is sometimes adulterated with a lead-laced chemical compound in Bangladesh, one of the world's predominant turmeric-growing regions.

Long banned from food products, lead is a potent neurotoxin considered unsafe in any quantity. A related analysis published recently confirms for the first time that turmeric is likely the primary contributor to elevated blood lead levels among Bangladeshis surveyed.

"People are unknowingly consuming something that could cause major health issues," said the papers' lead author Jenna Forsyth, a postdoctoral scholar at the Stanford Woods Institute for the Environment. "We know adulterated turmeric is a source of lead exposure, and we have to do something about it."

A longstanding problem

The first study, available online in Environmental Research, involves a range of analyses, including interviews with farmers and spice processors in several Bangladesh's districts, which together produce nearly half of the nation's turmeric. Many traced the issue to the 1980s when a massive flood left turmeric crops wet and relatively dull in color. Demand for bright yellow curry led turmeric processors to add lead chromate - an industrial yellow pigment commonly used to color toys and furniture - to their product. The practice continued as a cheap, fast way to produce a desirable color.

Potent neurotoxin

As a potent neurotoxin, lead increases the risk of heart and brain disease in adults and interferes with children's brain development. About 90 percent of children with elevated blood lead levels live in lower-income countries, and resulting cognitive damages are associated with nearly one trillion dollars in lost productivity annually.

"Unlike other metals, there is no safe consumption limit for lead, it's a neurotoxin in its totality," said the papers' senior author Stephen Luby, professor of medicine and the director of research for Stanford's Center for Innovation in Global Health. "We cannot console ourselves proposing that if the contamination were down to such and such level, it would have been safe."

The related study, published Sept. 17 in Environmental Science & Technology, looked at various potential sources of blood lead level contamination in Bangladeshis. Lead comes in various forms, called isotopes, and the ratios of those isotopes vary by the lead's origin. The researchers were able to fingerprint lead chromate-adulterated turmeric as the most likely culprit by matching it to lead isotopes in people's blood. The research is the first to directly link lead in turmeric to lead levels in blood.

Beyond Bangladesh

The researchers did not find direct evidence of contaminated turmeric beyond Bangladesh, and they point out that food safety checks by importing countries have incentivized large-scale Bangladesh spice processors to limit the amount of lead added to turmeric destined for export. However, the researchers caution, "the current system of periodic food safety checks may catch only a fraction of the adulterated turmeric being traded worldwide." In fact, since 2011, more than 15 brands of turmeric - distributed to countries including the U.S. - have been recalled due to excessive levels of lead.

While these recalls and previous studies found the presence of lead in turmeric, none clearly identified the source (some suggested it might be linked to soil contamination), proved the link to blood lead levels or revealed the problem's pervasiveness and incentives perpetuating it.

Toward solutions

Since 2014, Forsyth, Luby and Scott Fendorf, the Terry Huffington Professor in Stanford's School of Earth, Energy and Environment - co-authors on both papers - have worked in rural Bangladesh to assess lead exposure. With funding from the Stanford Woods Institute for the Environment, they first conducted a population assessment that found more than 30 percent of pregnant women had elevated blood lead levels.

The researchers now plan to focus on shifting consumer behaviors away from eating contaminated turmeric and reducing incentives for the practice. They suggest more effective and efficient drying technologies for turmeric processing. They also recommend that import inspectors around the world screen turmeric with X-ray devices that can detect lead and other chemicals.

Although few low-cost answers seem readily available in Bangladesh, the researchers suggest engaging consumers, producers and other stakeholders focused on food safety and public health could provide the seeds of a solution. To that end, Forsyth, Luby and Fendorf are part of an interdisciplinary project team, funded by the Stanford King Center on Global Development, seeking solutions to reduce lead exposure from turmeric, battery recycling and other sources in Bangladesh and beyond.

Among other goals, the team plans to develop business opportunities that reduce lead exposure. One team member, bioengineer Manu Prakash, is developing low-cost technologies to measure lead in turmeric, blood and other sources. Other collaborators, Shilajeet Banerjee and Erica Plambeck, are studying ways to shift demand and create business opportunities for lead-free turmeric.

"Jenna's remarkable work allows us to collaborate with stakeholders in Bangladesh to target effective prevention," Luby said.

Credit: 
Stanford University

Study finds potential therapeutic target for prostate cancers with PTEN mutation

PTEN, a tumor suppressor gene mutated in approximately 20% of primary prostate cancers, and in as many as 50% of androgen deprivation-resistant prostate cancers, relies on another gene, ARID4B, to function. These findings were published by George Washington University (GW) Cancer Center researchers in Nature Communications. This discovery provides a potential therapeutic target for prostate cancers carrying the common PTEN mutation.

"Loss of the tumor suppressor PTEN due to mutation or deletion not only is frequent in human prostate cancer, but also plays a large role in other cancers. We wanted to find out more about PTEN, and other genes it might rely on, to offer new treatment options for those with the PTEN mutation," said Ray-Chang Wu, PhD, associate professor of biochemistry and molecular medicine at the GW School of Medicine and Health Sciences. "We discovered that PTEN has an important connection to the gene ARID4B, which offers a new therapeutic target for treatment."

Wu, his co-author Mei-Yi Wu, PhD, associate professor of medicine at the GW School of Medicine and Health Sciences, and other members of the research team at the GW Cancer Center examined data from several prostate cancer cohorts and made an interesting observation: cancers which contain PTEN mutations almost always retain ARID4B. One function of the gene ARID4B includes remodeling the chromatin that makes up the chromosome. This "mutually exclusive" pattern between PTEN and ARID4B offers the team the first clue as to its potential importance in prostate cancer.

The research further found that suppression of ARID4B expression in cancer cells with PTEN mutation significantly inhibits cancer cell growth and increases cell death. In comparison, less pronounced effects were observed when cancer cells that contain functional PTEN were used, suggesting a dependence on ARID4B by PTEN-deficient prostate cancer. Importantly, the team is able to recapitulate these findings using the PTEN-deleted prostate cancer mouse models. As expected, deletion of PTEN alone in mice leads to development of prostate cancer. In stark contrast, mice with deletion of both PTEN and ARID4B do not develop tumors. Collectively, these results led the team to conclude that PTEN function depends on the presence of ARID4B and identify ARID4B as a potential therapeutic target in prostate cancer, given loss of the PTEN gene. More research is needed to develop methods to target ARID4B.

Credit: 
George Washington University

Machine learning could offer faster, more precise results for cardiac MRI scans

DALLAS, Sept. 24, 2019 - Cardiac MRI analysis can be performed significantly faster with similar precision to experts when using automated machine learning, according to new research published in Circulation: Cardiovascular Imaging, an American Heart Association journal.

Currently, analyzing heart function on cardiac MRI scans takes approximately 13 minutes for humans. Utilizing artificial intelligence in the form of machine learning, a scan can be analyzed with comparable precision in approximately four seconds.

Healthcare professionals regularly use cardiac MRI scans to make measurements of heart structure and function that guide patient care and treatment recommendations. Many important clinical decisions including timing of cardiac surgery, implantation of defibrillators and continuing or stopping cardiotoxic chemotherapy rely on accurate and precise measurements. Improving the performance of these measures could potentially improve patient management and outcomes.

In the UK, where the study was conducted, it is estimated that more than 150,000 cardiac MRI scans are performed each year. Based on the number of scans per year, researchers believe that utilizing AI to read scans could potentially lead to saving 54 clinician-days per year at each UK health center.

Researchers trained a neural network to read the cardiac MRI scans and the results of almost 600 patients. When the AI was tested for precision compared to an expert and trainee on 110 separate patients from multiple centers, researchers found that there was no significant difference in accuracy.

"Cardiovascular MRI offers unparalleled image quality for assessing heart structure and function; however, current manual analysis remains basic and outdated. Automated machine learning techniques offer the potential to change this and radically improve efficiency, and we look forward to further research that could validate its superiority to human analysis," said study author Charlotte Manisty, M.D. Ph.D. "Our dataset of patients with a range of heart diseases who received scans enabled us to demonstrate that the greatest sources of measurement error arise from human factors. This indicates that automated techniques are at least as good as humans, with the potential soon to be 'super-human'--transforming clinical and research measurement precision."

Although the study did not demonstrate superiority of AI over human experts and was not used prospectively for clinical assessment of patient outcomes, this study highlights the potential that such techniques could have in the future to improve analysis and influence clinical decision making for patients with heart disease.

Credit: 
American Heart Association

Racial/ethnic mortality disparities widen among many age groups

Ann Arbor, September 24, 2019 - Years of progress towards reducing disparities in racial/ethnic group mortality rates in the United States came to a halt between 2009 and 2012, according to a new study in the American Journal of Preventive Medicine, published by Elsevier. Prior to this inflection period, improvements in mortality rates within the African American population had largely been closing the gap. Since then, racial/ethnic mortality rate disparities have been widening rather than shrinking among many age groups, especially the very young and middle-aged.

"After years of progress in reducing racial/ethnic mortality disparities, our study shows that progress among most racial/ethnic and age groups has stalled and/or reversed in the US over the last decade. Alarmingly, we found that the mortality rate of infants and children was twice as high for African Americans than whites and is now on the rise again. While the mortality rate of middle-aged white Americans also increased in this period, the rate for the same age group among African Americans and American Indians remained substantially higher," explained lead investigator Keith P. Gennuso, PhD, University of Wisconsin Population Health Institute, University of Wisconsin-Madison, Madison, WI, USA. "The setback is particularly worrisome because it disproportionately affects those with historically poorer health who continue to face societal barriers."

This research project examined the size of racial/ethnic mortality disparities across age groups and investigated how changing mortality trends have affected these disparities. The extent of disparities was measured using between-group variance, a metric that summarizes the total gap between the mortality rates of five racial/ethnic groups (Asian, American Indian/Alaska Native, African American, Hispanic, and white) from the population average. Trend analysis was performed to examine how trends in between group variance changed over the most recent decade of mortality data.

Recent media coverage and research have focused on increasing mortality rates for middle-aged white Americans. This study confirms this alarming trend and recommends addressing its causes, such as the opioid epidemic, as a priority for public health policy. However, investigators also caution that it should not shift the focus away from the disproportionate health burden of other racial/ethnic and age-specific population subgroups.

Dr. Gennuso explained, "The findings of our research are important at this time because, taken together, they suggest that mortality trends among whites are important and influential to the overall mortality rate and racial/ethnic disparities, but they are not the whole story, especially for younger age groups. This study reinforces a strong body of prior research describing pervasive racial/ethnic disparities in mortality in the US."

The study concludes that effectively addressing the increasing disparities requires solutions that attend to root causes and the needs of specific age and racial/ethnic groups. "It will be important for us to apply lessons learned from our years of progress if we hope to regain what was lost and fully realize the Healthy People 2020 goal to achieve health equity, eliminate disparities, and improve the health of all groups," noted Dr. Gennuso.

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Elsevier

New technique to improve ductility of ceramic materials for missiles, engines

image: Purdue University researchers have developed a new process to help overcome the brittle nature of ceramics and make it more durable.

Image: 
Purdue University/Chris Adam

WEST LAFAYETTE, Ind. - Something as simple as an electric field could soon make wartime missiles or drinking mugs easier to produce and more resilient for fracture.

Items such as drinking mugs, missile heads, thermal barrier coatings on engine blades, auto parts, electronic and optic components are commonly made with ceramics.

The ceramics are mechanically strong, but tend to fracture suddenly when just slightly strained under a load unless exposed to high temperatures.

Purdue University researchers have developed a new process to help overcome the brittle nature of ceramics and make it more ductile and durable. The Purdue team calls the process "flash sintering," which adds an electric field to the conventional sintering process used to form bulk components from ceramics.

"We have been able to show that even at room temperatures, ceramics sintered with the electric field surprisingly deform plastically before fracture when compressed at high strain," said Haiyan Wang, the Basil S. Turner Professor of Engineering in Purdue's College of Engineering.

A study published in Science Advances demonstrates that applying an electric field to the formation of ceramics makes the material almost as easily reshaped as metal at room temperature. The Purdue team specifically applied its technique to titanium dioxide, a widely used white pigment.

"Nanotwins have been introduced in various metallic materials to improve strength and ductility. However, there are little prior studies that show nanotwins and stacking faults can significantly improve the plasticity of ceramics," said Jin Li, a postdoctoral fellow and researcher on the research team.

The significantly enhanced room temperature ductility in titanium dioxide is attributed to the unusually high-density defects, such as stacking faults, twins and dislocations, formed through the flash sintering process.

"The existence of these defects remove the need for defect nucleation in ceramics, which typically requires a large nucleation stress, greater than the fracture stress of ceramics," Wang said.

Li, the first author of the article from Purdue, said, "Our results are important because they open the door for using many different ceramics in new ways that can provide more flexibility and durability to sustain heavy loads and high temperatures without catastrophic brittle failure."

Improved plasticity for ceramics means more mechanical durability during operation at relatively low temperatures. The sample also could withstand almost as much compression strain as some metals do before cracks started to appear.

"These ductile ceramics find many technologically important applications," said Xinghang Zhang, professor of materials engineering and co-principle investigator on the research team. "It can be applied to defense operations, automobile manufacturing, nuclear reactor components and sustainable energy devices."

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Purdue University

New synthetic polymer degradable under very mild acidic conditions

image: Preparation of new degradable synthetic polymer.

Image: 
Ehime University

A research team in Ehime University prepared a new type of synthetic polymer, which can be degraded into a combination of well-defined low molecular weight compounds under very mild acidic conditions. The new polymer, poly(β-keto enol ether), has great potential to be utilized as an environmentally friendly material in the near future.

The research team, led by E. Ihara and H. Shimomoto, has been utilizing unique reactivities of a diazocarbonyl group for polymer synthesis where they have succeeded in preparing a variety of polymers with unprecedented chemical structures by the polymerization of some bis(diazocarbonyl) compounds bearing two diazocarbonyl groups in one molecule. Now they have found that three-component polymerization of an appropriated combination of a bis(diazocarbonyl) compound, bis(1,3-diketone), and tetrahydrofuran (THF) as monomers yields a new type of polymer structure containing the β-keto enol ether framework in the main chain, which has been known to be readily cleaved with a small amount of acid.

The polymerization catalyzed by a Rh catalyst proceeded as they expected, affording poly(β-keto enol ether) with a molecular weight higher than 10000. More importantly, the polymer was found to be cleanly degraded into a combination of two low molecular weight compounds in high yield under mild acidic conditions; one of the degraded products was the monomer itself, bis(1,3-diketone) (indicating recyclability of the monomer), and the other one was a dihydroxy compound derived from the bis (diazocarbonyl) compound and THF used as other monomers.

The acid-sensitivity of the β-keto enol ether framework of the polymer was so high that the degradation proceeded even in a chloroform solution because the solvent usually contains a very small amount of acid spontaneously generated from the solvent molecule under an ambient condition. On the other hand, in other solvents without an acidic trace, such as dimethylsulfoxide, the polymer did not degrade at all, demonstrating the extremely high sensitivity of the polymer structure to an acidic stimulus.

The highly acid-sensitive degradability can be useful for some important applications. For example, a drug-encapsulating material made of the polymer would release the incorporated active component by rapidly responding to a mild acidic environment. In addition, materials made of the polymer can be easily degraded to the above-described low molecular weight compounds, including one of the monomers, after they are used in neutral conditions. Synthetic polymers with such degradability are especially desired because of the serious environmental damage caused by non-degradable synthetic polymeric materials.

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Ehime University

Jackdaws learn from each other about 'dangerous' humans

image: Jackdaw

Image: 
Guill McIvor

Jackdaws can learn from each other to identify "dangerous" humans, new research shows.

The birds are known to recognise individual people, and respond differently to those they see as a threat.

In the new study, by the University of Exeter, a person unknown to the jackdaws approached their nest, and scientists played a recording of either a warning call or "contact calls" (suggesting no threat).

The next time the jackdaws saw this person, the birds that had heard the warning call reacted defensively by retuning more quickly to their nests.

"One of the big challenges for a lot of animals is how to live alongside humans," said lead author Victoria Lee, a PhD researcher at the Centre for Ecology and Conservation on Exeter's Penryn Campus in Cornwall.

"People can provide some benefits, such as the food at bird feeders, but in some cases humans are also a threat.

"Being able to discriminate between dangerous and harmless people is likely to be beneficial, and in this case we see jackdaws can learn to identify dangerous people without having had a bad experience themselves."

The study was carried out at three sites in Cornwall, focussing on 34 jackdaw nest boxes.

The jackdaws that were played a warning call on seeing a new human returned to their nest boxes more than twice as quickly (53%) on average when seeing that human again, whereas birds that heard contact calls took longer to return to their nest (63% on average).

Though jackdaws returned to their nests more quickly after seeing a human associated with a warning call, the calls did not appear to influence how long birds took to enter their nest box or how long they spent inside.

Credit: 
University of Exeter

Saw but forgot -- drivers' memory lapses puts motorcyclists at risk

image: Chloe Robbins, Ph.D. researcher in the driving simulator based at the University of Nottingham.

Image: 
Dr. Peter Chapman

There are an estimated 90 fatalities a year in the UK caused by drivers pulling out into the path of an oncoming motorcycle. New research by psychologists at the University of Nottingham suggests this sort of crash may often be the result of a short-term memory failure rather than the driver not seeing an approaching motorcycle.

A series of experiments, carried out in the School of Psychology's high-fidelity driving simulator, showed that drivers looked at, but seconds later failed to recall, critical approaching vehicles on up to 15% of occasions. Drivers were around 5 times more likely to forget a motorcycle compared with a car.

The research was funded by the ESRC and carried out by PhD student, Chloe Robbins supervised by Dr Peter Chapman, in the School of Psychology. It suggests that many 'Look but Fail to See' (LBFTS) crashes may have been misclassified and are more likely to be a case of 'Saw but Forgot' (SBF) errors.

"The 'Saw But Forgot' error: A role for short-term memory failures in understanding junction crashes?" has been published in the online journal PLOS ONE and offers practical interventions that may prevent SBF crashes in the future.

Short term memory failure

For each real-world crash there are hundreds of thousands of safe, successful, junction crossings, but when errors do occur they can have fatal consequences. To understand what is going on the research team explored where drivers looked and what they remembered while crossing junctions in a driving simulator. The big surprise from the research was the fact that some drivers have absolutely no recollection of seeing an oncoming vehicle at all even as they are about to pull out at a junction.

Their results suggest that it's what happens in the moments between seeing an approaching vehicle and pulling out that can lead to a complete absence of memory - particularly for approaching motorcycles.

Dr Chapman, an expert in the psychology of driving, said: "Typical interpretations of the LBFTS crash are based on the idea that the driver pulling out has failed to devote sufficient attention to the traffic on the road. Our study set out to look for systematic biases in attention towards and memory for different vehicle types. Although these effects were found, the most striking finding was not subtle biases in vision or memory, but the fact that in some cases there was a complete absence of memory, particularly for approaching motorcycles."

Study 1: Stopping at a junction

The research team recorded the eye movements of 60 drivers crossing junctions in the University of Nottingham's high fidelity driving simulator - part of NITES (the Nottingham Integrated Transport and Environment Simulation facility). Although drivers seemed to look in the right places as they approached the junction, there were 20 occasions where a driver couldn't remember one of the oncoming vehicles. The forgotten vehicle was a LGV on 2 occasions, a car on 4 occasions and a motorcycle on 14 occasions.

Study 2: Pulling out of the junction

For this study 30 drivers were required to approach a series of junctions and go straight on, if they thought it was safe to do so. The simulation of oncoming vehicles involved either 2 cars or a car and a motorcycle. The driver's eye movements were tracked continuously throughout the experiment and memory tests were only given if the driver actually pulled out in front of oncoming vehicles. Out of the 120 times memory was tested drivers failed to report a car on one occasion and a motorcycle on 8 occasions.

Study 3: Tracking head and eye movements

This experiment used the same design as study 2 but now 45 drivers wore lightweight eye-tracking glasses to obtain highly accurate measures of exactly where they looked before pulling out. Out of the 180 memory tests drivers failed to report a car on 3 occasions and a motorcycle on 16 occasions. Of these 16 memory failures there were 5 occasions when the driver had not looked directly at the oncoming motorcycle. These could be examples of typical LBFTS (Look but Fail to See) errors where the driver looked in the right direction but failed to see the motorcycle. In contrast, on the remaining 11 occasions the driver clearly looked directly at the oncoming motorcycle, but couldn't remember it a few seconds later. The researchers have described these as SBF (Saw but Forgot) errors.

This study also showed that SBF errors were associated with more head movements and a longer gap between fixating on the motorcycle and pulling out. The researchers suggest that this is where the forgetting is occurring. Things the driver looks at between seeing the oncoming vehicle and pulling out might be overwriting the initial contents of visuospatial memory so information about the oncoming vehicle is no longer available at the time a decision is made to pull out.

Dr Chapman said: "These studies compellingly demonstrate that even in safety-critical situations it is possible to observe dramatic failures of visual memory. These 'Saw but Forgot' errors were remarkably frequent in the simulator and we have every reason to think that they may be equally prevalent in the real world. The surprising lack of memory may be exactly why these crashes appear so mysterious."

The phonological loop - 'See bike say bike'

As a result of their findings the research team has established a new framework to understand dynamic risky decision-making with an emphasis on the role of short-term memory in such situations. The 'Perceive Retain Choose' (PRC) model creates new predictions and proposals for practical interventions.

Specifically, they suggest teaching drivers that if they see a motorcycle approaching, they should say so out loud - 'See Bike, Say Bike'.

Dr Chapman said: "If relevant visual information is encoded phonologically it has been shown that it is no longer subject to visuospatial interference. Clearly any research that improves our understanding of these crashes and the kind of countermeasures that can be used to prevent them, has the potential to be a major contribution to world health."

Credit: 
University of Nottingham

Doctors are not using tools to help youths quit smoking

BOSTON (September 23, 2019) --At a time when the rapid growth in electronic cigarette "vaping" among young people threatens to reverse decades of progress in reducing tobacco use, a large study published today in JAMA Pediatrics finds that medical professionals are largely failing to use existing tools to help young people quit smoking.

Medicaid data from more than 80,000 adolescents and young adults diagnosed with nicotine use disorder indicated that only four percent had received counseling to encourage them to stop using tobacco products, only 1.2 percent were prescribed medications to help them quit, and only one in 1,000 got both counseling and treatment, a combination that could double or triple their chances of quitting.

"We have treatments that are proven to work for older people and are very likely to work for young people as well. Not using these treatments is a missed opportunity," says Nicholas Chadi, MD, MPH, a pediatrician at Boston Children's Hospital and first author on the paper.

Nicotine, the main active ingredient in most tobacco products, is highly addictive. An estimated 20-30 percent of all smokers develop nicotine use disorder, unable to give it up and suffering withdrawal symptoms if they try. Its potential health effects are well known, and youth have an additional risk because their brains are still developing.

For 15 years or more, the American Academy of Pediatrics has issued periodic guidelines concerning the use of tobacco products in children. They urge pediatricians to ask their patients whether they or family members smoke or use electronic cigarettes, advise them on the dangers of tobacco products, encourage them to stop and, for those who are addicted, offer medication to help them quit. Among the medical options are nicotine replacement therapy (tapering doses of nicotine delivered via skin patch, gum, or lozenge) and two other drugs: bupropion and varenicline.

But are these things being done? To find out, Chadi and colleagues tapped a database of some 3.5 million Medicaid patients, between the ages of 10 and 22, across 11 states. Over an 18-month period in 2014 and 2015, 3.8 percent of patients had been diagnosed with nicotine use disorder. Among a smaller group of patients that had six months of follow-up after diagnosis, 95 percent had received no treatment or counseling related to their nicotine use disorder.

Nicotine use on the rise

The team hopes the paper will help persuade health care professionals -- including pediatricians, nurse practitioners, and school health providers -- to take advantage of interventions at their disposal, especially in light of the recent resurgence in nicotine use through electronic cigarettes.

"As providers, we have a tremendous opportunity here to intervene and help prevent future generations of people dealing with the long-term health consequences of nicotine use disorder," said Scott Hadland, MD, MPH, MS, senior author on the report, and a pediatrician and addiction specialist at Boston Medical Center's Grayken Center for Addiction. "We have tools that we know are effective in helping curb nicotine addiction, and we need to get these tools into the appropriate hands."

Adolescent smoking had dropped nearly five-fold since the Surgeon General's 1964 report warning of the health risks. But in the last decade, the soaring popularity of e-cigarettes has driven up youth tobacco use. E-cigarette use among high school students rose nearly 80 percent in a single year, from 2017 to 2018, as new vaping devices, candy-like flavors, and youth-oriented marketing campaigns enticed one out of every five students to try them.

Even more worrisome, in Canada a similar rise in e-cigarette use was accompanied by a 50 percent increase in the use of traditional cigarettes in a single year. The team's fear is that we'll soon see the same trend in the U.S., as students start out on e-cigarettes because they're cheap, fun and readily available, and then switch to regular cigarettes when the nicotine cartridge runs out. That could lead to a "new nicotine epidemic" among America's youth, Chadi says, erasing recent progress.

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Boston Children's Hospital

Scientists track frog-killing fungus to help curb its spread

image: This Rhacophorus bimaculatus frog, a native of the Philippines that makes its home in the misty spray zones beneath waterfalls, is one of the many frog species imperiled by the deadly chytrid fungus.

Image: 
Photo by Rafe Brown & Jason Fernandez

Berkeley -- From habitat loss to climate change, amphibians around the world face immense threats to their survival. One emerging and sinister threat is the chytrid fungus, a mysterious pathogen that kills amphibians by disrupting the delicate moisture balance maintained by their skin, and that is decimating frog populations around the world.

"Amphibians are already one of the most imperiled groups on the planet, and this fungal disease is further threatening their biodiversity," said Erica Bree Rosenblum, an associate professor of environmental science, policy and management at the University of California, Berkeley.

With the help of advanced genetic testing and hundreds of frog skin swabs, Rosenblum, along with UC Berkeley graduate student Allison Byrne and an international team of collaborators, has created the most complete map to date of when and where different genetic variants of the fungus -- analogous to different strains of viruses like the flu -- have infected frog populations around the world.

Some of these genetic variants are deadlier than others, so knowing their current geographic distribution is key to preventing future spread of the disease, the researchers said. The investigation also uncovered a whole new genetic lineage of the fungus, one that appears to have originated in Asia and may be the oldest variant yet discovered.

"An invisible aspect of globalization is that when we move plants and animals around, we are moving their diseases around, and that can have really devastating consequences," Rosenblum said. "If we know what lineages are where, we can better predict conservation outcomes, because some of these lineages are really deadly, and others less so."

The study appears online the week of Sept. 23 in the journal Proceedings of the National Academy of Sciences.

Tracking an emergent pathogen

"Chytrid" is the name of not one, but around 1,000 different species of fungi, most of which are harmless detritivores that spend their lives munching away on dead and rotting organic matter. The frog-killing variety, which bears the tongue-twisting name Batrachochytrium dendrobatidis, wasn't discovered until the late 1990s, when scientists were desperately searching for the source of disturbing frog die-offs that had been popping up worldwide since the 1970s.

Though researchers now have a culprit, much remains unknown about this enigmatic disease: Some species of frog, like the American Bullfrog, are not affected by the fungus, while for others, exposure to the fungus means almost certain death.

Scientists are also not clear on the origins of the frog-killing chytrid species. It may have been lurking in some corner of the planet for thousands of years and only brought to worldwide attention when global trade of frogs for their meat and for lab experiments exposed new populations to the pathogen. On the other hand, it's possible that a recent genetic mutation in the fungus suddenly made it more virulent, Rosenblum said.

"Not all amphibian species are equally susceptible, not all strains of the fungus are equally deadly, and there are a lot of open questions about the disease. Are humans moving it around? Are different strains coming together and mixing and becoming even more deadly?" Rosenblum said. "It's like a murder mystery we are trying to solve."

To find the answers, researchers often turn to genetic testing to "get under the hood" of a disease, using DNA signatures to map out different variants of a pathogen and trace them back to their source. But full genome sequencing of the chytrid fungus is notoriously difficult, requiring large samples of the fungus that must be grown and cultured in a lab and that sometimes involve killing the infected frog.

In the current study, Byrne borrowed technologies from medical research to create a new genetic test that can determine what variant of the fungus a frog has using only a skin swab. Rather than sequencing the entire genome, the test looks only at key snippets of DNA that help distinguish one variant from another. Because it only relies on small snippets, it requires much less DNA overall.

"People have been using Q-tip swabbing to test simply whether the pathogen is present or not, but now we can use the same swabs to figure out genetic details about the fungus, too," Rosenblum said. "There are literally hundreds of thousands of these swabs sitting in people's freezers around the world. Now, from these skin swabs, we can figure out not just that this frog is infected, but specifically what lineage of the disease it carries. Is it the same lineage that infects the frog living next door, or in another country, or across the world?"

Mapping a fungus through space and time

Rosenblum and Byrne partnered with collaborators around the world to analyze 222 fungus samples collected from 24 different countries. These samples included skin swabs collected in the field, as well as some taken from preserved museum frog specimens, the oldest of which dates to 1984.

"I think something that our collaborators are most excited about is going back in time with these museum specimens," Byrne said. "You can take an amphibian in a jar, collected a hundred years ago, swab it and now start to really build the picture of how these lineages have spread."

The analysis revealed the distribution of the four known lineages around the globe and uncovered a whole new lineage that appears to have originated in Asia. It also showed how, in many places, different lineages of the pathogen appear to live side-by-side. This is a frightening prospect, as recent lab work has hinted that, like many human viruses, different lineages of the pathogen can mix and become deadlier.

Policies that limit the transport of frogs and other animals across international borders could help prevent the spread of the disease, the researchers say. For example, restrictions on salamander imports from Europe have so far kept a related species of the fungus, Batrachochytrium salamandrivorans, out of the United States.

"We are seeing that policy actions can slow or prevent the spread of these diseases," Byrne said. "I think there might be a little bit of complacency around the fact that this chytrid is basically everywhere. But now we know that they are not all the same, the risks depend on what lineage is there, and then when you get this mixing of lineages, you could have many unintended consequences."

Credit: 
University of California - Berkeley

Method discovered to reactivate tumour fighting genes 'silenced' by cancer

Scientists at UCL have developed a method to reactivate 'tumour suppressor' genes, which are switched off by cancer cells - a finding which could lead to new targeted biotherapies for cancer.

In the study, published in Nature Structural and Molecular Biology, researchers at UCL Cancer Institute and the Cancer Research UK UCL Centre aimed to identify ways to block the function of a regulatory protein called PRC2 (Polycomb repressive complex 2).

Healthy cells use PRC2 to silence genes whose instructions should only be read by other cell types. Cancer cells 'hijack' this silencing function of PRC2 to switch off 'tumour suppressor' genes. When active, these genes stop cells from dividing, so if PRC2 could be removed from these genes it could halt tumour growth.

Using healthy cells grown in the lab, the researchers found that PRC2 also binds to RNA, the information molecule that is produced by active genes. When PRC2 binds RNA, it can no longer bind and silence the gene.

Using cancer cells in the lab, the researchers used a protein called dCas9 (Cas9 endonuclease dead) to attach RNA to silenced tumour suppressor genes. The RNA specifically removed PRC2 from the tumour suppressor gene to which it was attached, reactivating the gene and stopping the cancer cells from dividing.

Lead author, Professor Richard Jenner (UCL Cancer Institute), said: "Our discovery provides a way to precisely reverse cancerous gene silencing events, while leaving other genes switched off as they are supposed to be.

"The next steps are to test which cancer types this could be applied to and to develop a method that could be used to deliver the RNA and gene targeting agent to cancer cells in patients."

Credit: 
University College London

Discovery of novel cancer signaling mechanism and design of new anticancer compound

image: Scientists uncover novel signaling mechanism in cancer and also propose new channel of treatment

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© Tokyo University of Science

Of the various different functions that proteins perform in a cell, a crucial one is the recognition and transmission of certain "signals," collectively referred to as signal transduction. Receptors (proteins) on the cell surface recognize certain molecules and then initiate a chain of biochemical events inside the cell. These biochemical events are responsible for cellular activities such as multiplication, survival, etc. Needless to say, any perturbation of this "biochemical signaling" can be extremely detrimental to the cell, even leading to cancer in some cases. But, it is possible to target defective biochemical signaling pathways within a cell to treat cancer, provided the underlying mechanisms are studied thoroughly. This is exactly what a group of scientists from Japan set out to do in their study published in Cell Communication and Signaling. This research group--whose study was supported by Japan Agency for Medical Research and Development (AMED)--was headed by Assoc. Prof. Yuuki Obata from Tokyo University of Science (also National Cancer Center), and consists of Prof. Isamu Shiina (Tokyo University of Science), Prof. Ryo Abe (Tokyo University of Science and Teikyo University), Dr. Toshirou Nishida (National Cancer Center), and Prof. Koji Okamoto (National Cancer Center).

A certain signaling receptor protein called KIT tyrosine kinase functions in the growth and survival of different types of cells, including hematopoietic cells (the progenitors of all blood cells), mast cells (a type of immune cells), and interstitial cells of Cajal (electrical pacemakers in gastrointestinal tract). Active mutations of this protein have been identified in several cancers, such as mast cell leukemia (MCL), gastrointestinal stromal tumor (GIST), and acute myeloid leukemia (AML). In MCL, the mutations D816V (human) and D814Y (mouse) are frequently found; here, the mutated KIT protein "mislocalizes" in a cellular compartment called the "endolysosome" (EL). In GIST, mutated KIT accumulates in and conducts cancer-specific signaling from the Golgi, the site in a cell where macromolecules are produced, modified, and packaged, especially proteins. Active KIT mutations have been found in about 10% of core binding factor AML (CBF-AML) patients; these are also associated with poor prognosis in AML. However, it remains unclear whether KIT transduces signals from intracellular compartments in AML. The research group from Japan aimed to answer this question by using a newly synthesized compound called M-COPA (along with other existing ones) that targets intracellular transport. According to them, this also represents an attractive strategy to combat cancer. Prof Shiina candidly says, "We wanted to investigate the anticancer effect of the new anticancer drug lead compound M-COPA synthesized at our university against hematological cancers (leukemia, lymphoma, etc.)."

Apart from D816V, another major active KIT mutation in AML is N822K. D816V has been characterized extensively, but the signaling platforms and mechanisms of N822K are relatively unknown. Also, before this study, it was unclear how the mutated KIT and where the downstream signaling molecules are activated. The scientists investigated the relationship between the localization of KITN822K (KIT protein carrying the N822K mutation) and its activation in an AML cell line, Kasumi-1. The scientists found that in AML cells, KITN822K mislocalized to and accumulated in the EL. Newly produced KIT in the endoplasmic reticulum (ER) travels to the cell membrane via the Golgi and then relocates to EL. However, immunofluorescence experiments (those that use antibodies against the mutated KIT, tagged with fluorescent dyes for identification) showed that KIT was activated in the Golgi. KIT activation on the Golgi was also found in other leukemia cells that have the receptor mutation.

Next, Prof. Shiina and colleagues found that in the Golgi in AML cells, KITN822K also activates downstream signaling proteins called AKT, ERK, and STAT5. They did this by using specific compounds that target intracellular transport of proteins: brefeldin A (BFA), 2-methylcoprophilinamide (M-COPA) (inhibitors of transport from ER to the Golgi), and monensin (inhibitor of Golgi export). They found that in cells treated with BFA or M-COPA, KIT was retained in the ER. This also decreased the auto-phosphorylation of KIT and thereby its downstream signaling. Suppression of Golgi export of KIT using monensin did not suppress the KIT signals, which told the scientists that mutated KIT carries out cancer signaling specifically at the Golgi.

So, what are the future applications of this study? Small molecule TKIs (tyrosine kinase inhibitors) and antibodies against RTKs (receptor tyrosine kinases) have been developed to suppress cancer proliferative signaling using mechanisms similar to the ones described above. According to Prof. Shiina and the group, this study reveals that the novel compound M-COPA can be used to block transport of KIT from the ER to the Golgi (where it is activated and carries out downstream oncogenic signaling). The scientists say that the compound M-COPA has applications such as treatment of patients with AML, improved prognosis for these patients, and improvement in the quality of life of these patients. Prof. Shiina concludes by stating, "Currently, the synthesis of various M-COPA analogs is progressing every day at our university, and their inhibitory effects against hematological cancers and solid cancers (stomach cancer, lung cancer, ovarian cancer, etc.) are being verified."

Credit: 
Tokyo University of Science

Soap from straw -- Scientists develop eco friendly ingredient from agricultural waste

image: Pictured here is Dr. Pattanathu Rahman, microbial biotechnologist from the University of Portsmouth and Director of TeeGene.

Image: 
University of Portsmouth

A scientist has discovered a way of using one of the world's most abundant natural resources as a replacement for manmade chemicals in soaps and thousands of other household products.

An innovative research project, published this month and led by the University of Portsmouth, has demonstrated that bails of rice straw could create a 'biosurfacant', providing an alternative non-toxic ingredient in the production of a vast variety of products that normally include synthetic materials which are often petroleum based.

The biotechnology project set out to solve one of the planet's most pressing environmental problems, looking for a way of reducing the amount of manmade chemicals in everyday life. It has been co-supervised by the University of Portsmouth's Centre for Enzyme Innovation, working in conjunction with Amity University in India and the Indian Institute of Technology.

The study was looking for a natural replacement for chemical surfactants, a main active ingredient in the production of cleaning products, medicine, suncream, make-up and insecticides. The surfactant holds oil and water together, helping to lower the surface tension of a liquid, aiding the cleaning power and penetration of the product.

Dr Pattanathu Rahman, microbial biotechnologist from the University of Portsmouth and Director of TeeGene, worked with academics and PhD Scholar Mr Sam Joy from 2015 to create a biosurfacant by brewing rice straw with enzymes. The scientists believe this environmentally friendly method results in a high quality ingredient that manufacturing industries are crying out for.

Dr Rahman said: "Surfactants are everywhere, including detergent, fabric softener, glue insecticides, shampoo, toothpaste, paint, laxatives and make up. Imagine if we could make and manufacture biosurfacants in sufficient quantities to use instead of surfactants, taking the manmade chemical bonds out of these products. This research shows that with the use of agricultural waste such as rice straws, which is in plentiful supply, we are a step closer."

Scientists behind the research believe the use of biosurfactants created from rice straw or other agricultural waste could have a positive ecological effect in a number of ways:

There is significant concern about the impact of the chemical surfactants used in household products, most of which ends up in the oceans.

Rice straw is a natural by-product of the rice harvest, with millions of tonnes created worldwide every year.

Farmers often burn the waste producing harmful environmental emissions. Using it to create another product could be an efficient and beneficial recycling process.

There could also be an economic advantage to using biosurfacants produced from agricultural waste.

Dr Rahman explains: "The levels of purity needed for biosurfactants in the industries in which they're used is extremely high. Because of this, they can be very expensive. However, the methods we have of producing them make it much more economical and cost efficient. It's a very exciting technology with tremendous potential for applications in a range of industries."

The study shows that biosurfactants could be a potential alternative for the synthetic surfactant molecules, with a market value of $US2.8 billion in 2023. The considerable interest in biosurfactants in recent years is also due to their low toxicity, biodegradable nature and specificity, which would help them meet the European Surfactant Directive.

Dr Rahman says the process of producing biosurfacants calls for new attitudes to soap and cleaning products.

He explains: "Most people consider soap to be an effective means of removing bacteria from their skin. However, we have flipped this concept on its head by discovering a way to create soap from bacteria. They have anti-microbial properties suitable for cosmetic products and biotherapeutics. This approach will channelise the majority of the waste management solutions and could create new job opportunities."

Credit: 
University of Portsmouth

Improvements to rheology measurements in reservoirs proposed by Kazan Federal University

image: Viscosity/shear rate dependency

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Kazan Federal University

KFU's In-Situ Combustion Lab has been in charge of the project since 2016. Senior Research Associate Irek Mukhamatdinov is the project head. The team also includes Lab Head Alexey Vakhin and Junior Research Associate Firdavs Aliev. A number of publications, including a master thesis ("Study of the rheological and wetting properties of polymer solutions based on polyacrylamides" by Anabel Sosa Acosta), have appeared since then.

The development and implementation of innovative integrated methods to increase oil recovery is one of the key approaches to solving existing problems in the oil industry. Residual oil in the water-filled formations is kept stationary by surface capillary forces on the scale of individual pores and low permeability inclusions, as well as viscous forces on the scale of low-permeability differences and layers of the formation. One of the reasons for the low coefficient of displacement and formation coverage by the water-flooding process in fields containing high viscosity oil is the large ratio of oil and water viscosities, which leads to a decrease in the coverage of the formation with a displacing agent. The addition of a high molecular weight polymer to water makes it possible to increase the viscosity of water and improve the ratio of the mobility of oil and water, thus increasing oil recovery. The nature of the wettability of the pore surface of a reservoir rock determines filtration processes. The displacement coefficient is determined by the consolidated action of a number of factors, such as porosity, permeability, heterogeneity of the pore space structure, and pore size distribution.

One of the most important and fundamental characteristics of the microstructure of porous media in oil-bearing formations is the wettability of their surface. The specificity of the displacement of oil by polymer solutions, the state and distribution of residual oil saturation in the formation, and the dominant goal of stimulating the formation to reduce residual oil reserves depend on the wettability of the porous medium.

The study established the properties of reservoir rocks of various types to determine the optimal operating conditions of the field. The physico-chemical properties of the interfaces of various phases and the laws of their interaction are characterized by a number of indicators - surface tension at the interface, phenomena of wettability and spreading, adhesion and cohesion, and heat of wetting. The properties of the contacting phases and the patterns of their interaction along the surface tension of formation fluids on various surfaces were also studied. The surface tension at the rock-liquid, rock-gas interface is practically inaccessible for measurement, and indirect methods are used, in particular, wettability is studied.

The results obtained for the studied polymer solutions confirm the significant influence of the chemical nature of the mineral skeleton of the reservoir rock on their viscosity, and hence on the efficiency of application to increase oil recovery. Laboratory selection of an effective polymer and its optimal concentration can be carried out according to the proposed methodological approach. This technique complements the use of filtration experiments, which are much longer and more expensive. Therefore, preliminary screening on a large number of polymer variants and their concentrations is important.

This work contributes to the development of an understanding of phenomena at interfaces in oil and gas reservoirs at the micro level, and gives a clearer picture of the physics of the wetting process.

Based on the results of laboratory tests, field trials of various polymer compositions of the established concentration will be recommended.

Further development of the topic will be carried out in the direction of studying wetting and rheological properties at various temperatures and pressures close to reservoir conditions, as well as on real oil-saturated rocks.

Credit: 
Kazan Federal University

A new way to turn heat into energy

COLUMBUS, Ohio -- An international team of scientists has figured out how to capture heat and turn it into electricity.

The discovery, published last week in the journal Science Advances, could create more efficient energy generation from heat in things like car exhaust, interplanetary space probes and industrial processes.

"Because of this discovery, we should be able to make more electrical energy out of heat than we do today," said study co-author Joseph Heremans, professor of mechanical and aerospace engineering and Ohio Eminent Scholar in Nanotechnology at The Ohio State University. "It's something that, until now, nobody thought was possible."

The discovery is based on tiny particles called paramagnons--bits that are not quite magnets, but that carry some magnetic flux. This is important, because magnets, when heated, lose their magnetic force and become what is called paramagnetic. A flux of magnetism--what scientists call "spins"--creates a type of energy called magnon-drag thermoelectricity, something that, until this discovery, could not be used to collect energy at room temperature.

"The conventional wisdom was once that, if you have a paramagnet and you heat it up, nothing happens," Heremans said. "And we found that that is not true. What we found is a new way of designing thermoelectric semiconductors--materials that convert heat to electricity. Conventional thermoelectrics that we've had over the last 20 years or so are too inefficient and give us too little energy, so they are not really in widespread use. This changes that understanding."

Magnets are a crucial part of collecting energy from heat: When one side of a magnet is heated, the other side--the cold side--gets more magnetic, producing spin, which pushes the electrons in the magnet and creates electricity.

The paradox, though, is that when magnets get heated up, they lose most of their magnetic properties, turning them into paramagnets--"almost-but-not-quite magnets," Heremans calls them. That means that, until this discovery, nobody thought of using paramagnets to harvest heat because scientists thought paramagnets weren't capable of collecting energy.

What the research team found, though, is that the paramagnons push the electrons only for a billionth of a millionth of a second--long enough to make paramagnets viable energy-harvesters.

The research team--an international group of scientists from Ohio State, North Carolina State University and the Chinese Academy of Sciences (all are equal authors on this journal article)--started testing paramagnons to see if they could, under the right circumstances, produce the necessary spin.

What they found, Heremans said, is that paramagnons do, in fact, produce the kind of spin that pushes electrons.

And that, he said, could make it possible to collect energy.

Credit: 
Ohio State University