Earth

Boosted signal

First introduced into wide use in the middle of the 20th century, nuclear magnetic resonance (NMR) has since become an indispensable technique for examining materials down to their atoms, revealing molecular structure and other details without interfering with the material itself.

"It's a broadly used technique in chemical analysis, materials characterization, MRI -- situations in which you do a non-invasive analysis, but with atomic and molecular details," said UC Santa Barbara chemistry professor Songi Han. By placing a sample in a strong magnetic field and then probing it with radio waves scientists can determine from the response from the oscillating nuclei in the material's atoms the molecular structure of the material.

"However, the problem with NMR has been that because it's such a low-energy technique, it's not very sensitive," Han said. "It's very detailed, but you don't get much signal." As a result, large amounts of sample material may be needed relative to other techniques, and the signals' general weakness makes NMR less than ideal for studying complex chemical processes.

One remedy to this situation lies in dynamic nuclear polarization (DNP), a popular technique in which energy is "borrowed" from nearby electrons to enhance the signal emanating from the nuclei.

"Electrons have much higher energy than nuclei," Han explained. Built into specially-designed "radical" molecules, these unpaired electrons' polarization is transferred to the nuclei to improve their signal.

As hot a topic as DNP has become in the past decade, however, Han thinks we're still just scratching the surface.

"Despite DNP fundamentally changing the landscape of NMR, at the end of the day, only a handful of designer polarizing agents have been used," Han said. "A polarizing agent has been used to polarize hydrogen nuclei, but the power of DNP is greater than that. In principle, many other sources of electron spin can polarize many other types of nuclear spin."

In a paper published in the journal Chem, Han and colleagues push the boundaries of NMR with the first demonstration of dynamic nuclear polarization using the transition metal vanadium (IV). According to Han, their new approach -- dubbed "hyperfine DNP spectroscopy" -- offers a glimpse into the typically obscure local chemistry around transition metals, which are important for processes such as catalysis and reduction-oxidation reactions.

"Now we may be able to use endogenous metals that are present in catalysts and in many other important materials," Han said, without having to add polarizing agents -- those radical molecules -- to produce a stronger NMR signal.

The irony with transition metals such as vanadium and copper, Han explained, is that those atoms tend to tend to be functional centers -- places where important chemistry takes place.

"And those exact action centers and functional centers have been very difficult to analyze (with NMR) because they tend to become invisible," she said. The electron spins in the transition metal tend to shorten the lifetime of the NMR signal, she explained, making them disappear before they can be detected.

This wouldn't be the first time chemistry around transition metals has been observed, Han said, pointing to studies that looked at the chemical environments around gadolinium and manganese. But the commercially-available instrument used in those studies offered "a very narrow view."

"But there are many more metals that are much more important for chemistry," she said. "So we developed and optimized instrumentation that enhances the frequency range from the very narrow scope of a commercial instrument to a much broader range."

With their hyperfine DNP spectroscopy the researchers also found that the signal is indeed wiped out within a certain region around the metal called the spin diffusion barrier, but if the nuclei are located outside that zone the signal becomes visible.

"There are ways to lighten up that environment, but you need to know how and why," Han said, adding that the paper's co-lead authors, Sheetal Kumar Jain of UC Santa Barbara and Chung-Jui Yu of Northwestern University will continue to explore and apply this new method as they pursue their academic and research careers.

Credit: 
University of California - Santa Barbara

Biochar from agricultural waste products can adsorb contaminants in wastewater

UNIVERSITY PARK, Pa. -- Biochar -- a charcoal-like substance made primarily from agricultural waste products -- holds promise for removing emerging contaminants such as pharmaceuticals from treated wastewater.

That's the conclusion of a team of researchers that conducted a novel study that evaluated and compared the ability of biochar derived from two common leftover agricultural materials -- cotton gin waste and guayule bagasse -- to adsorb three common pharmaceutical compounds from an aqueous solution. In adsorption, one material, like a pharmaceutical compound, sticks to the surface of another, like the solid biochar particle. Conversely, in absorption, one material is taken internally into another; for example, a sponge absorbs water.

Guayule, a shrub that grows in the arid Southwest, provided the waste for one of the biochars tested in the research. More properly called Parthenium argentatum, it has been cultivated as a source of rubber and latex. The plant is chopped to the ground and its branches mashed up to extract the latex. The dry, pulpy, fibrous residue that remains after stalks are crushed to extract the latex is called bagasse.

The results are important, according to researcher Herschel Elliott, Penn State professor of agricultural and biological engineering, College of Agricultural Sciences, because they demonstrate the potential for biochar made from plentiful agricultural wastes -- that otherwise must be disposed of -- to serve as a low-cost additional treatment for reducing contaminants in treated wastewater used for irrigation.

"Most sewage treatment plants are currently not equipped to remove emerging contaminants such as pharmaceuticals, and if those toxic compounds can be removed by biochars, then wastewater can be recycled in irrigation systems," he said. "That beneficial reuse is critical in regions such as the U.S. Southwest, where a lack of water hinders crop production."

The pharmaceutical compounds used in the study to test whether the biochars would adsorb them from aqueous solution were: sulfapyridine, an antibacterial medication no longer prescribed for treatment of infections in humans but commonly used in veterinary medicine; docusate, widely used in medicines as a laxative and stool softener; and erythromycin, an antibiotic used to treat infections and acne.

The results, published today (Nov. 16) in Biochar, suggest biochars made from agricultural waste materials could act as effective adsorbents to remove pharmaceuticals from reclaimed water prior to irrigation. However, the biochar derived from cotton gin waste was much more efficient.

In the research, it adsorbed 98% of the docusate, 74% of the erythromycin and 70% of the sulfapyridine in aqueous solution. By comparison, the biochar derived from guayule bagasse adsorbed 50% of the docusate, 50% of the erythromycin and just 5% of the sulfapyridine.

The research revealed that a temperature increase, from about 650 to about 1,300 degrees F in the oxygen-free pyrolysis process used to convert the agricultural waste materials to biochars, resulted in a greatly enhanced capacity to adsorb the pharmaceutical compounds.

"The most innovative part about the research was the use of the guayule bagasse because there have been no previous studies on using that material to produce biochar for the removal of emerging contaminants," said lead researcher Marlene Ndoun, a doctoral student in Penn State's Department of Agricultural and Biological Engineering. "Same for cotton gin waste -- research has been done on potential ways to remove other contaminants, but this is the first study to use cotton gin waste specifically to remove pharmaceuticals from water."

For Ndoun, the research is more than theoretical. She said she wants to scale up the technology and make a difference in the world. Because cotton gin waste is widely available, even in the poorest regions, she believes it holds promise as a source of biochar to decontaminate water.

"I am originally from Cameroon, and the reason I'm even here is because I'm looking for ways to filter water in resource-limited communities, such as where I grew up," she said. "We think if this could be scaled up, it would be ideal for use in countries in sub-Saharan Africa, where people don't have access to sophisticated equipment to purify their water."

The next step, Ndoun explained, would be to develop a mixture of biochar material capable of adsorbing a wide range of contaminants from water.

"Beyond removing emerging contaminants such as pharmaceuticals, I am interested in blending biochar materials so that we have low-cost filters able to remove the typical contaminants we find in water, such as bacteria and organic matter," said Ndoun.

Credit: 
Penn State

A change of heart -- new drug for HCM reduces heart mass

image: A new drug being tested for hypertrophic cardiomyopathy changed the structure of the heart in a clinical trial.

Image: 
Stephanie King/ Michigan Medicine

For the first time, a medication has impacted heart muscle thickness and function for patients with the most common inherited heart condition, rather than simply addressing their symptoms.

"This is the first study to show a favorable impact of a medication on cardiac structure and function in any form of hypertrophic cardiomyopathy," says Sara Saberi, M.D., an assistant professor of internal medicine and a cardiologist at the Michigan Medicine Frankel Cardiovascular Center.

Current options, Saberi explains, might help patients feel better today, but they don't help them live longer, nor do they prevent people from experiencing heart failure down the road. They also don't affect any of the heart structural abnormalities that define the disease: thickness of the heart muscle, resultant stiffness and abnormalities in other cardiac structures.

"There's a huge void. HCM is a chronic progressive disease that still does not have a cure," Saberi says.

She presented the results of her team's EXPLORER-HCM CMR sub-study at the 2020 American Heart Association Scientific Sessions, which published simultaneously in Circulation.

Addressing the underlying cause of HCM

In HCM, the motor proteins interact with each other too much, causing over-vigorous squeeze of the muscle and causing stiffness of the muscle.

A medication designed specifically for HCM, mavacamten, is currently being studied in a variety of clinical trials. It's part of a new class of drugs called cardiac myosin inhibitors. The medication works by blocking a protein called myosin from interacting too much with other motor proteins, which then allows the heart muscle to squeeze and relax more normally, Saberi explains. It is effective at reducing obstruction to blood flow within the heart that can occur with the disease.

"It's the first class of medications that actually targets the underlying pathophysiology of HCM."

The primary measure for this study, the mass of the heart, was significantly reduced in those patients taking the drug as opposed to those taking placebo, Saberi says.

In September, Saberi and colleagues published findings from the EXPLORER-HCM randomized controlled trial in The Lancet. The patients had significant improvements in obstruction to blood flow in the heart and said they felt better after taking the drug for 30 weeks. They showed improvements in markers like exercise capacity. Now, this substudy explores some of the reason why people may be feeling better, Saberi says.

Results from cardiac imaging

The substudy was done using imaging of the study participants' hearts.

"Cardiac MRI has such incredible visual and spatial resolution that you can accurately examine the heart's mass, volume, ejection fraction, or how well the blood is pumping, and fibrosis, which is the scar burden in the heart muscle," Saberi says.

Her team observed these encouraging results after just 30 weeks of treatment, which would be a plus for patients, Saberi says.

"It's also encouraging that we don't see a worsening in fibrosis along with the normalization in ejection fraction," she says. Patients originally had a very high ejection fraction, but after treatment it moved into the normal range.

Although HCM is considered a rare disease, it affects about one in 500 people, Saberi says, so there's a large need for more effective therapeutics.

The EXPLORER-HCM trial was a phase three trial that studied the use of mavacamten in obstructive HCM, and has moved into a five-year open-label extension. A concurrent phase two trial, MAVERICK-HCM, investigated safety and tolerability in non-obstructive HCM. Those participants are also in the five-year open-label extension study now. Saberi says a phase three trial that would look at how well it works for those patients with non-obstructive HCM would be the next step.

The medication is not currently available outside of a clinical trial setting, Saberi says.

Credit: 
Michigan Medicine - University of Michigan

Study shows geographic shift in U.S. social mobility

Dylan Connor's father worked as a house painter while his mother tended to their home and family, one that included six boys. Neither of his parents finished high school, but they built a future for their children that included their success. This may sound like a story made in America.

But Connor is from Ireland. He is now an assistant professor at Arizona State University's School of Geographical Sciences and Urban Planning where he studies social mobility, the chances that children who are born into poverty can climb out of poverty as adults.

Social mobility differs considerably from country to country. The United States was once exceptional when it came to social mobility but is not anymore compared with other countries, like Canada, Ireland and Sweden. The landscape has shifted unevenly over the last century with some areas of the U.S. scoring high in social mobility and others scoring low, some persistently so. Connor's recent study on the subject paints a picture of what social mobility currently looks like in the U.S. and how it has shifted over the last century.

"Just within the last five or six years, we've realized that there is great variation within the U.S. in terms of how places provide opportunity," said Connor, co-author of the study.

His study, "The changing geography of social mobility in the United States," is published online in the Proceedings of the National Academy of Sciences. Michael Storper, distinguished professor of Regional and International Development in Urban Planning at the University of California, Los Angeles, is a co-author of the paper.

To find out what social mobility looks like, Connor and Storper built a data set consisting of 2 million children counted in the 1920 and 1940 censuses. The researchers followed them from childhood through adulthood tracking their social mobility, noting which geographical areas have improved, which areas have declined and what it is about those areas that determined their respective fates.

The researchers divided the country into six regions: Northeast, South, Midwest, West, northern plains and mountains, and southern plains and mountains.

They found that in the early 20th century, the industrial corridor in the Northeast and Midwest and the West provided the greatest opportunities for social mobility. But lately, the urban Midwest has not fared well.

"What we're seeing is that, in relative terms, the urban areas of the Midwest have gotten a lot worse," said Connor. "There's been a real collapse in the urban Midwest in terms of social mobility."

In contrast, Minnesota, Utah and the northern central plains have shown gains in social mobility. "The children growing up there seem to be doing relatively well, and that wasn't necessarily true in the past," said Connor. Previously, many of those children would have stayed and often worked in agriculture, but now the children growing up there are benefiting from their communities and schooling.

"One of the interesting things we noticed about kids growing up in the upper Midwest and the northern plains is that they're quite likely to move away," said Connor. "They're taking their skills to other labor markets and using them there. But kids growing up in poverty in the South seem to be less likely to do that."

The South has shown stubbornly low levels of social mobility over time." It's an interesting case, because the South actually gained a lot of jobs over the 20th century," said Connor. "A lot of manufacturing jobs have gone there, but upward mobility hasn't improved in the same way."

The study also shows that white children in the South fare worse than white kids elsewhere. That may be because in a more socially divided place, people are less willing to fund local schools or contribute to the communal good because they don't see themselves benefiting from it, said Connor.

In essence, what the study is showing is that a lot of change in social mobility is driven by changing economic fortunes over time, like the shift of jobs to different places. "The Midwest is a classic image of that," said Connor.

"You had an industrialized area, a lot of manufacturing jobs, but they're no longer there in the same numbers," explained Connor. "The jobs have moved abroad to countries like China or to the U.S. South and Southwest. So, a lot of the change in the landscape is about changing economic fundamentals, whereas the persistence of low social mobility in the South, for example, is also driven by forces that have even deeper roots, like racial inequality, and these forces can feed back on the family structures and schooling experiences of people who grow up there."

Connor's study shows that to improve social mobility, both job availability and community issues, like schooling, healthcare, and racial segregation must be addressed.

"Those issues have much more power in predicting social mobility than average incomes or the number of highly sophisticated jobs in a local labor market," he said. "We're never going to be in a position where economic opportunity is going to be spread evenly over the country. It's never been the case and it probably never will be. But I think that a healthy society is one that produces lots of geographical mobility and intergenerational social mobility."

Credit: 
Arizona State University

Cannabis strength soars over past half century -- new study

New research shows that over the past 50 years street cannabis across the world has become substantially stronger carrying an increased risk of harm.

The team behind the study from the Addiction and Mental Health Group at the University of Bath, synthesised data from over 80,000 cannabis samples tested in the past 50 years from street samples collected in the USA, UK, Netherlands, France, Denmark, Italy and New Zealand. Their findings are published in the journal Addiction and the research was funded by the Society for the Study of Addiction.

The researchers investigated how concentrations of THC (the intoxicating component of cannabis responsible for giving users a 'high') had changed over time in different types of cannabis. In herbal cannabis, they found that THC concentrations increased by 14% from 1970 to 2017. This was primarily due to a rising market share of stronger varieties such as sinsemilla relative to traditional herbal cannabis which contains seeds and less THC.

The team have previously found consistent evidence that frequent use of cannabis with higher levels of THC carries an increased risk of problems such as addiction and psychotic disorders.

Lead author Dr Tom Freeman, Director of the Addiction and Mental Health Group at the University of Bath said: "As the strength of cannabis has increased, so too has the number of people entering treatment for cannabis use problems. More Europeans are now entering drug treatment because of cannabis than heroin or cocaine."

The researchers found that the increases in THC were particularly high for cannabis resin, with THC concentrations rising by 24% between 1975 and 2017. Cannabis resin is extracted from herbal cannabis and is now typically stronger than herbal cannabis according to the findings.

They also looked at concentrations of cannabidiol or CBD, which is not intoxicating but may have potential medical uses such as helping people to quit cannabis. In contrast to THC, they found no evidence for changes in CBD in cannabis over time.

Study co-author Sam Craft also from the Addiction and Mental Health Group at the University of Bath explained: "Cannabis resin - or 'hash' - is often seen as a safer type of cannabis, but our findings show that it is now stronger than herbal cannabis. Traditionally, cannabis resin contained much lower amounts of THC with equal quantities of CBD, however CBD concentrations have remained stable as THC has risen substantially, meaning it is now much more harmful than it was many years ago."

Cannabis is the most widely used illicit drug in the world but has recently been legalised in Canada, Uruguay and several states in the USA. The findings of this new study have particular relevance in light of growing demands to legalise cannabis in an attempt to make it safer. Most recently a referendum in New Zealand (which ultimately failed to receive public support) included measures to limit the strength of cannabis sold through legalisation.

The researchers argue that increases in cannabis strength highlight the need to implement wider strategies for harm reduction similar to those used for alcohol - such as standard units and public guidelines on safer consumption limits.

Dr Tom Freeman added: "As the strength of cannabis has risen, consumers are faced with limited information to help them monitor their intake and guide decisions about relative benefits and risks. The introduction of a standard unit system for cannabis - similar to standard alcohol units - could help people to limit their consumption and use it more safely."

Credit: 
University of Bath

STRENGTH trial finds new fish oil medication did not reduce the risk of cardiac events

DALLAS, Nov. 15, 2020 -- The fish oil-based medication known as omega-3 carboxylic acids or omega-3 CA did not decrease the risk of cardiac events compared to a placebo, according to late-breaking research presented today at the American Heart Association's Scientific Sessions 2020. The virtual meeting is Friday, November 13-Tuesday, November 17, 2020, and is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care worldwide.

Fish oil supplements containing the omega-3 fatty acids eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) are commonly taken to prevent or reduce complications of heart disease.

A 2017 American Heart Association Science Advisory noted that omega-3 fish oil supplements prescribed by a health care professional may help prevent death from heart disease in patients who recently had a heart attack and may prevent death and hospitalizations in patients with heart failure. However, there is a lack of scientific research to support clinical use of these supplements to prevent heart disease in the general population.

"Many people continue to take fish oil supplements to prevent heart disease. However, the fish oil medication we tested in the STRENGTH trial was not effective for that purpose," said lead author A. Michael Lincoff, M.D., vice chairman for Research of the Department of Cardiovascular Medicine and an interventional cardiologist in the Heart, Vascular & Thoracic Institute at the Cleveland Clinic.

"We believe the questions surrounding the benefit versus risk of fish oil will remain unanswered unless another trial using a neutral placebo such as corn oil is able to definitively show cardiovascular benefits for an omega-3 fatty acid medication," he said.

This phase III international study evaluated omega-3 CA in 13,078 adults at 675 centers in 22 countries. The patients were all being treated with cholesterol-lowering statins and had either blockages of the arteries to the heart, brain or legs or were at increased risk for heart disease due to other medical conditions such as diabetes or lifestyle risk factors such as smoking.

Participants were randomly assigned to receive either 4 grams of the omega-3 CA medication or the corn oil placebo daily. Researchers compared the rate of cardiovascular death, heart attack, stroke, need for coronary revascularization (stenting or bypass surgery) or hospitalization for unstable angina for all patient groups.

The study began in 2014 and was stopped slightly early, in January 2020, because preliminary results of the study deemed it unlikely to prove the benefit omega-3 CA medication. Over a median follow up time of about three years, 1,580 patients experienced at least one cardiac event. There were no significant differences in the number of patients experiencing cardiac events between the two treatment groups. Additionally, a potentially dangerous abnormal heart rhythm (atrial fibrillation) occurred more frequently among patients taking the omega-3 CA medication than in those receiving the control corn oil.

Credit: 
American Heart Association

The right tune for blood

image: Repetitive elements induce a RIG-I-like receptor-mediated inflammation that regulates the emergence of hematopoietic stem and progenitor cells. Lefkopoulos et al. report that repetitive element (RE) RNA present during developmental hematopoiesis activates the RIG-I-like receptor pathway to provide the inflammatory signals necessary for HSPC formation. The RE RNA is depicted as cables that fuel the 'DJ controller' with electricity. RIG-I and MDA5 function as decks for the controller to play music, which represents the inflammatory signals turning into blood cells, whereas LGP2 functions as a mixer by controlling the levels of inflammation RIG-I and MDA5 provide. Nature is all-inclusive, like a rainbow.

Image: 
llustration concept by M. Derecka, Marika ki and ET. Cover art by @kostispavlou.

Hematopoietic stem cells can replenish all the different cell types of our blood system. For this reason, hematopoietic stem cells are the cells used in many blood diseases when patients need transplantations. Thus, our ability to generate, amplify and maintain these cells is important for human health. The lab of Eirini Trompouki at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, in collaboration with scientists the Albert Einstein College of Medicine, the University of Trento and the Chinese Academy of Sciences, discovered a novel mechanism that enhances hematopoietic stem cell formation during development. They showed that RNA from repetitive elements, remnants of viruses integrated through evolution into the genome of many animals, is produced during hematopoietic development. Repetitive element RNAs activate innate immune receptors to induce inflammation - the good kind - and increase the formation of embryonic hematopoietic stem cells.

Hematopoietic stem cells are the foundation of the blood system from fish to humans and give rise to leukocytes for fighting off pathogens, erythrocytes for transferring oxygen to tissues, and every other cell type that can be found in our blood. Importantly, hematopoietic stem cells born during development are also the foundation of our blood system when we are adults and their improper function can lead to multiple blood diseases. Therefore, hematopoietic stem cells are precious both in sickness and in health and understanding the mechanisms that govern their formation during development can help simply: "make blood".

Repetitive element RNA enhances HSC formation

During the process of embryonic hematopoiesis in zebrafish, the lab of Eirini Trompouki found small bits of RNA expressed from a part of the genome considered as "junk DNA". "Contrary to what many people believe, genes only comprise a very small part of our genome. The largest part of it contains other sequences, among which many are the remnants of viruses accumulated within the vertebrate genome through years of infections and evolution. Such sequences are for example several types of the so-called repetitive elements that usually remain repressed", explains Eirini Trompouki, Max Planck group leader and member of the Centre for Integrative Biological Signalling Studies, Cluster of Excellence at the University of Freiburg.

To investigate the possible role of these RNA molecules in hematopoietic stem cell formation, the team used chemicals that enhance the expression of repetitive elements or injected a repetitive element copy RNA in zebrafish embryos. These experiments resulted in an increase in hematopoietic stem cell numbers generated within injected embryos. The next question of the team was how do repetitive elements exert their function in hematopoietic development? They hypothesized that, since these RNAs are viral remnants, they might be sensed by cell proteins that are normally used to sense everyday viral infections.

One of the key sensors of viral infection is the RIG-I-like receptor (RLR) family, which establishes a host response once activated by such a pathogen. Eirini and her team thought that in order to prove that repetitive elements are sensed by RLRs they needed to show that the increase in HSC numbers, observed upon chemical induction or overexpression of repetitive elements should not happen if RLRs are missing from the cells. Indeed, the team showed that injection of the same repetitive element RNA copy could not enhance hematopoietic stem cell development in RLR-deficient zebrafish embryos, which proved that the influence of these RNAs on hematopoietic stem cell generation depends on the presence and function of RLRs.

Functions of RLRs in hematopoiesis

The researchers then reasoned that if the function of repetitive elements in hematopoiesis depends on RLRs, then ablation of RLRs should have an impact on hematopoietic stem cell biology. The RLR family includes three different members, namely RIG-I, MDA5 and LGP2. In their experiments, the team showed that the absence of either Rig-I or Mda5 severely reduced the numbers of hematopoietic stem cells born in zebrafish embryos.

On the contrary, the absence of the third family member, Lgp2, increased the numbers of hematopoietic stem cells. "In every organism, for every process to be maintained within normal healthy boundaries and especially during development, we always need a switch setting the process on, but also a switch setting the process off or containing it. In this case, it seems that the RLR family can function as an independent system that involves both the positive and negative regulatory mechanisms", says Stelios Lefkopoulos on the dual role of the receptor family in hematopoiesis.

Repetitive RNA activates viral sensors

Knowing the role of RLRs in hematopoiesis, the team next tackled the question how these receptors regulate hematopoietic stem cell generation. They found that when they reduced the levels of either Rig-I or Mda5 in their experiments, inflammatory signals beneficial for hematopoietic stem cells were downregulated, whereas when they reduced the Lgp2 levels these signals were upregulated. These observations explained how Rig-I or Mda5 normally induce, whereas Lgp2 impairs developmental hematopoiesis.

"All these events constitute a novel mechanism modulating hematopoiesis. Hematopoietic stem cells originate in embryos from endothelial cells of the aorta. It therefore seems that during the transition from one cell type to the other, different repetitive elements are expressed. One can speculate that while this transition is happening, newly expressed repetitive elements are sensed by RLRs and thus, actively participate in shaping the developmental fate by orchestrating inflammation signals", says Eirini Trompouki.

A universal mechanism of tissue generation and integrity?

Since repetitive elements and RLRs are also expressed in other non-blood cells, it could be possible that a similar mechanism can be pertinent in more setups and conditions such as other tissues, stem cells or for adult hematopoiesis. "Nature never maintains through evolution something that is of no use; these repetitive elements have been maintained within vertebrate genomes for a reason, and we now know that activating RLRs and regulating developmental hematopoiesis is one of them," says Stelios Lefkopoulos.

Credit: 
Max-Planck-Gesellschaft

Go (over) easy on the eggs: 'Egg-cess' consumption linked to diabetes

image: Eat one or more eggs per day and your risk of diabetes increases by 60 per cent.

Image: 
Pixabay/Myruams-Fotos

Scrambled, poached or boiled, eggs are a popular breakfast food the world over. Yet the health benefits of the humble egg might not be all they're cracked up to be as new research from the University of South Australia shows that excess egg consumption can increase your risk of diabetes.

Conducted in partnership with the China Medical University, and Qatar University, the longitudinal study (1991 to 2009) is the first to assess egg consumption in a large sample of Chinese adults.

It found that people who regularly consumed one or more eggs per day (equivalent to 50 grams) increased their risk of diabetes by 60 per cent.

With the prevalence of diabetes in China now exceeding 11 per cent - above that of the global average of 8.5 per cent - diabetes has become a serious public health concern.

The economic impact of diabetes is also significant, accounting for 10 per cent of global health expenditure (USD $760 billion). In China, diabetes-related costs have exceeded USD $109 billion.

Epidemiologist and public health expert, UniSA's Dr Ming Li, says the rise of diabetes is a growing concern, especially in China where changes to the traditional Chinese diet are impacting health.

"Diet is a known and modifiable factor that contributes to the onset Type 2 diabetes, so understanding the range of dietary factors that might impact the growing prevalence of the disease is important," Dr Li says.

"Over the past few decades China has undergone a substantial nutritional transition that's seen many people move away from a traditional diet comprising grains and vegetables, to a more processed diet that includes greater amounts of meat, snacks and energy-dense food.

"At the same time, egg consumption has also been steadily increasing; from 1991 to 2009, the number of people eating eggs in China nearly doubled*.

"While the association between eating eggs and diabetes is often debated, this study has aimed to assess people's long-term egg consumption of eggs and their risk of developing diabetes, as determined by fasting blood glucose.

"What we discovered was that higher long-term egg consumption (greater than 38 grams per day) increased the risk of diabetes among Chinese adults by approximately 25 per cent.

"Furthermore, adults who regularly ate a lot of eggs (over 50 grams, or equivalent to one egg, per day) had an increased risk of diabetes by 60 per cent."

The effect was also more pronounced in women than in men.

Dr Li says that while these results suggest that higher egg consumption is positively associated with the risk of diabetes in Chinese adults, more research is needed to explore causal relationships.

"To beat diabetes, a multi-faceted approach is needed that not only encompasses research, but also a clear set of guidelines to help inform and guide the public. This study is one step towards that long-term goal."

Credit: 
University of South Australia

Manchester group discover new family of quasiparticles in graphene-based materials

image: The image features a doping vs magnetic field conductance map: The magnetic field is varied along the vertical axis. Horizontal Yellow streaks show propagation of Brown-Zak fermions, propagating along straight trajectories with high mobility (low resistance), whereas slanted indigo lines show the cyclotron motion around Brown-Zak fermions. The slope of these lines enabled us to get the degeneracy (and find an additional quantum number) of these new quasiparticles.

Image: 
Julien Barrier, The University of Manchester http://julienbarrier.eu/resources/

A group of researchers led by Sir Andre Geim and Dr Alexey Berdyugin at The University of Manchester have discovered and characterised a new family of quasiparticles named 'Brown-Zak fermions' in graphene-based superlattices.

The team achieved this breakthrough by aligning the atomic lattice of a graphene layer to that of an insulating boron nitride sheet, dramatically changing the properties of the graphene sheet.

The study follows years of successive advances in graphene-boron nitride superlattices which allowed the observation of a fractal pattern known as the Hofstadter's butterfly - and today (Friday, November 13) the researchers report another highly surprising behaviour of particles in such structures under applied magnetic field.

"It is well known, that in zero magnetic field, electrons move in straight trajectories and if you apply a magnetic field they start to bend and move in circles", explain Julien Barrier and Dr Piranavan Kumaravadivel, who carried out the experimental work.

"In a graphene layer which has been aligned with the boron nitride, electrons also start to bend - but if you set the magnetic field at specific values, the electrons move in straight line trajectories again, as if there is no magnetic field anymore!"

"Such behaviour is radically different from textbook physics." adds Dr Piranavan Kumaravadivel.

"We attribute this fascinating behaviour to the formation of novel quasiparticles at high magnetic field," says Dr Alexey Berdyugin. "Those quasiparticles have their own unique properties and exceptionally high mobility despite the extremely high magnetic field."

As published in Nature Communications (doi: 10.1038/s41467-020-19604-0), the work describes how electrons behave in an ultra-high-quality superlattice of graphene with a revised framework for the fractal features of the Hofstadter's butterfly. Fundamental improvements in graphene device fabrication and measurement techniques in the past decade have made this work possible.

"The concept of quasiparticles is arguably one of the most important in condensed matter physics and quantum many-body systems. It was introduced by the theoretical physicist Lev Landau in the 1940s to depict collective effects as a 'one particle excitation'," explains Julien Barrier "They are used in a number of complex systems to account for many-body effects."

Until now, the behaviour of collective electrons in graphene superlattices were thought in terms of the Dirac fermion, a quasiparticle that has unique properties resembling photons (particles with no mass), that replicate at high magnetic fields. However, this did not account for some experimental features, like the additional degeneracy of the states, nor did it match the finite mass of the quasiparticle in this state.

The authors propose 'Brown-Zak fermions' to be the family of quasiparticles existing in superlattices under high magnetic field. This is characterised by a new quantum number that can directly be measured. Interestingly, working at lower temperatures allowed them to lift the degeneracy with exchange interactions at ultra-low temperatures.

"Under the presence of a magnetic field, electrons in graphene start rotating with quantised orbits. For Brown-Zak fermions, we managed to restore a straight trajectory of tens of micrometres under high magnetic fields up to 16T (500,000 times earth's magnetic field). Under specific conditions, the ballistic quasiparticles feel no effective magnetic field," explain Dr Kumaravadivel and Dr Berdyugin.

In an electronic system, the mobility is defined as the capacity for a particle to travel upon the application of an electrical current. High mobilities have long been the Holy Grail when fabricating 2D systems such as graphene because such materials would present additional properties (integer and fractional quantum hall effects), and potentially allow the creation of ultra-high frequency transistors, the components at the heart of a computer processor.

"For this study we prepared graphene devices that are extra-large with a very high level of purity". says Dr Kumaravadivel. This allowed us to achieve mobilities of several millions of cm²/Vs, which means particles would travel straight across the entire device without scattering. Importantly, this was not only the case for classical Dirac fermions in graphene, but also realised for the Brown-Zak fermions reported in the work.

These Brown-Zak fermions define new metallic states, that are generic to any superlattice system, not just graphene and offers a playground for new condensed matter physics problems in other 2D material based superlattices.

Julien Barrier added "The findings are important, of course for fundamental studies in electron transport, but we believe that understanding quasiparticles in novel superlattice devices under high magnetic fields can lead to the development of new electronic devices."

The high mobility means that a transistor made from such a device could operate at higher frequencies, allowing a processor made out of this material to perform more calculations per unit of time, resulting in a faster computer. Applying a magnetic field would usually scale down the mobility and make such a device unusable for certain applications. The high mobilities of Brown-Zak fermions at high magnetic fields open a new perspective for electronic devices operating under extreme conditions.

Credit: 
University of Manchester

Food allergies take a greater emotional toll on Asian families

image: The ACAAI Annual Scientific Meeting is virtual this year!

Image: 
ACAAI

ARLINGTON HEIGHTS, Ill (November 13, 2020) - Studies have shown that food allergies negatively affect the quality of life of those who suffer with them. A new study being presented at this year's virtual American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting reveals the impact on food allergy quality of life (FAQOL) for Asian patients and their parents is significantly higher than for other races.

"Based on our questionnaire, Asian parents of children with food allergy living in the U.S. had a mean score of 50.5, indicating a 'fairly' negative impact on quality of life, which was significantly higher than white and Black parents," says Christine Rubeiz, MD, ACAAI member and lead author of the study. "White and Black parents had mean scores of 40.4 and 40.9 respectively, corresponding closer to the food allergy having 'a little bit' of a negative impact on quality of life."

The study examined 6829 questionnaires filled out at Cincinnati Children's Hospital Medical Center as part of a retrospective chart review. The questionnaires were scored from 0-100, with higher scores corresponding to worse quality of life.

"Our study showed Asian parents had significantly higher scores (worse QOL) in both higher and lower socioeconomic groups," says allergist Amal Assa'ad, MD, ACAAI member and senior author of the study. "Most studies of Asian children have been done in Asia, where the prevalence of food allergy is 3-8%. Some estimates of food allergy in the general U.S. population report a similar prevalence, about 8%. Asian families with food allergy appear to have worse food allergy-related-quality of life compared to other races, according to our research. This highlights the need for further studies on the impact of food allergy on Asian families, who may be an underrecognized population."

According to Dr. Rubeiz, "We found other significant racial disparities in FAQOL scores, particularly with Black and Hispanic patients. Within the Medicaid population, we found that Black and Hispanic patients and parents had significantly higher scores (worse quality of life) compared to white patients and parents. Cultural food preferences and the financial burden of food allergy may be a factor in this finding."

Credit: 
American College of Allergy, Asthma, and Immunology

First non-human primate study showing promise of gene therapy for stroke repair

image: Astrocyte-converted neurons in monkey brain after stroke

Image: 
Jinan University

Stroke is a leading cause of death and severe long-term disability with limited treatment available. A research team led by Prof. Gong Chen at Jinan University, Guangzhou, China recently reported the first non-human primate study demonstrating successful in vivo neural regeneration from brain internal glial cells for stroke repair. This work was published on Frontiers in Cell and Developmental Biology on November 5th, 2020.

"Current treatment of ischemic stroke mainly aims at restoring blood flow and neuroprotection, typically with a narrow time window of several hours. However, many stroke patients cannot reach hospital within a few hours after the onset of stroke, and may suffer from a large number of neuronal death and loss of brain functions. Therefore, how to regenerate functional new neurons after stroke is the key to restore brain functions", said Ms. Long-Jiao Ge, the first author of the work and a PhD student in the Institute of Zoology, Chinese Academy of Sciences.

"We have previously published a series of works demonstrating that overexpression of a single neural transcriptional factor NeuroD1 can directly convert glial cells into neurons in mouse brains. However, most clinical trials on stroke have failed in the past decades, suggesting that successful rodent studies may not be sufficient for clinical translation. Because in vivo glia-to-neuron conversion is such an innovative technology, we decided to take an important step to further validate this new technology in non-human primates", Prof. Chen explained the original intention of this work.

In this study, Prof. Chen and his team first established an ischemic stroke model in rhesus macaque monkeys aged from 9 to 21 years old to capture the typical occurrence of stroke among senior population of humans. Using astrocyte promoter GFAP to control the expression of neural transcriptional factor NeuroD1, Chen's team demonstrates successfully that reactive astrocytes caused by ischemic stroke in the monkey brain can be efficiently converted into neurons. "We are very happy to see that the neuronal density in NeuroD1-treated areas is consistently higher than that not treated with NeuroD1", said Ge proudly.

"An unexpected finding is that a class of interneurons, that are sensitive to stroke injury, are significantly protected after NeuroD1 treatment, accompanied by a significant reduction of neuroinflammation. This result has important implication that in vivo astrocyte-to-neuron conversion not only regenerates new neurons but also protects the injured neurons from secondary damage, preventing further neuronal loss. Such findings of combinatorial effects of neuroregeneration plus neuroprotection may have profound impact on brain repair", said Prof. Chen.

"What we have developed here is a unique gene therapy, using adeno-associated virus (AAV) vectors to deliver transgene NeuroD1 through direct intracranial injection into the ischemic region in primate brains. Different from classical gene therapies aiming for correction of gene mutations, our gene therapy regenerates new neurons, making it a kind of gene therapy-mediated cell therapy. We call it neuroregenerative gene therapy", Prof. Chen commented on this innovative new technology.

"This study in non-human primates opens a new avenue using neuroregenerative gene therapy to repair damaged brains, which brings new hope to millions of patients suffering from stroke and other neurological disorders," concluded Prof. Chen.

Credit: 
Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University

CMIP6 adds more value in simulating extreme temperatures in China

image: Sunset at Beihai Park

Image: 
Kexin CHEN

Against the background of global warming, more intense and frequent heat waves have brought huge impacts on humanity. As such, the characteristics of extreme temperature changes in the future have become a key concern of the climate change community. Climate models have provided an avenue for studying the possible changes in extreme temperatures in the future; and in this respect, to ease of comparison across models from different modelling groups worldwide, the World Climate Research Programme (WCRP) established the Coupled Model Intercomparison Project (CMIP), which is devoted to providing standardized climate simulation outputs for intercomparison purposes. However, there are still large uncertainties in the simulation results of different models. Particularly, when simulating temperature extremes in China, what the differences are between the models of the previous CMIP phase (CMIP5) and their more advanced versions in the current phase (CMIP6) is an important question.

Towards addressing this, researchers from Beijing Normal University selected 27 models from CMIP6 and CMIP5, respectively, and calculated eight extreme temperature indices as defined by the Expert Team on Climate Change Detection and Indices. The simulation performances of different models in terms of their temporal and spatial distributions of extreme temperature were compared, and the results have recently been published in Atmospheric and Oceanic Science Letters.

According to this study, the CMIP6 models reproduce the spatial distributions of the annual maxima of the daily maximum temperature, annual minima of the daily minimum temperature, and frost days, better than CMIP5. However, the CMIP6 models still possess low skill in capturing warm days and cold nights, and in particular produce obvious cold biases or warm biases over the Tibetan Plateau. Furthermore, different versions of models from the same model organization were compared, and the advanced CMIP6 models were found to show no significant differences from their CMIP5 counterparts for some models.

Overall, compared to CMIP5 models, CMIP6 offers improved ways of simulating extreme temperatures in China. The simulation capabilities of some individual models in CMIP6 are obviously better than those of most other models. We can therefore trust these CMIP6 models to drive regional models to perform downscaling studies and project future extreme temperature changes.

Credit: 
Institute of Atmospheric Physics, Chinese Academy of Sciences

Wolves alter wetland creation and recolonization by killing ecosystem engineers

Beavers are some of the world's most prolific ecosystem engineers, creating, maintaining and radically altering wetlands almost everywhere they live. But what, if anything, might control this engineering by beavers and influence the formation of North America's wetlands?

In a paper to be published Friday in the journal Science Advances, researchers with the University of Minnesota's Voyageurs Wolf Project and Voyageurs National Park observed and demonstrated that wolves affect wetland ecosystems by killing beavers leaving their colonies to create new ponds.

Beavers are important ecosystem engineers that create wetlands around the world, storing water and creating habitat for numerous other species. This study documents that wolves alter wetland creation when they kill beavers that have left home and created their own dams and ponds.

Juvenile beavers disperse alone and often create new ponds or fix up and recolonize existing, old ponds. By studying pond creation and recolonization patterns along with wolf predation on beavers, project biologists and co-authors Tom Gable and Austin Homkes found that 84% of newly-created and recolonized beaver ponds remained occupied by beavers for more than one year. But when a wolf kills the beaver that settles in a pond, no such ponds remain active.

This relationship between wolves and dispersing beavers shows how wolves are intimately connected to wetland creation across the boreal ecosystem and all the ecological processes that come from wetlands.

"How large predators impact ecosystems has been a matter of interest among scientists and the public for decades," said Gable, project lead of the Voyageurs Wolf Project. "Because wolves are the apex predators in northern Minnesota and beavers are ecosystem engineers, we knew there was potential for wolves to affect ecosystems by killing beavers."

Researchers found that wolves can have this impact on wetlands without necessarily changing the abundance or behavior of beavers. This newly supported link between wolf predation, dispersing beavers and wetlands may have long-lasting impacts for boreal landscapes and habitat for other species. The Voyageurs Wolf Project is investigating the long-term effects of this relationship.

"In 2015, we documented a wolf killing a dispersing beaver in a newly-created pond," said Homkes, a field biologist with the Voyageurs Wolf Project. "Within days of the wolf killing the beaver, the dam failed because there was no beaver left to maintain it. The wolf appeared to have prevented the beaver from turning this forested area into a pond. This initial observation was fascinating and we realized we needed to figure out how wolves were connected to wetland creation in the Greater Voyageurs Ecosystem."

After five years of intensive fieldwork, Gable, Homkes and colleagues have estimated that wolves altered the establishment of about 88 ponds per year and the storage of over 51 million gallons of water annually in the Greater Voyageurs Ecosystem. The pond observed in 2015 still has not been colonized by another beaver, said Gable, who visited the site in mid-September 2020.

"Our work hints at the possibility that wolves might have a longer-term impact on wetland creation and generate habitat patchiness that supports many other species across the landscape, but we need to study this mechanism further," said Joseph Bump, co-author and associate professor in the University's Department of Fisheries, Wildlife, and Conservation Biology.

Wolves and large predators are usually thought to have outsized ecological effects primarily by reducing the abundance of their prey or by altering the behavior of their prey through fear of predation, both of which allow predators to indirectly impact lower parts of the food chain such as vegetation, songbirds and other wildlife. Some research has even claimed wolves impact river ecosystems through trophic cascades, but this has been met with substantial skepticism and remains hotly debated among scientists.

"The fact that we have convincingly shown wolves can impact wetlands without necessarily changing the abundance or behavior of beavers is a really exciting finding," said co-author Sean Johnson-Bice, a project collaborator from the University of Manitoba.

"The Greater Voyageurs Ecosystem sits within a flat landscape that is dominated by water and trees, creating the perfect conditions that currently support some of the highest beaver densities in North America," said Voyageurs National Park wildlife researcher and co-author Steve Windels.

"Though we don't have evidence that wolves are limiting the size of the beaver population in Voyageurs, understanding the nuanced and complex ways that predators and prey affect one another and their environment is critical to fulfilling the National Park Service's mission to protect and preserve our resources for future generations."

This study identified a novel and unique way by which predators influence ecological processes, which ultimately enriches our understanding of the diverse roles predators play in ecosystems.

"There are a number of good reasons to maintain and restore healthy predator populations and this study should be helpful for understanding the full role and therefore value of predators, especially when they eat ecosystem engineers," Bump said.

Credit: 
University of Minnesota

Most type 2 diabetes patients are at high risk of a fatal heart attack or stroke

Sophia Antipolis, 14 Nov 2020: Preventing heart attacks and strokes in type 2 diabetes patients managed in primary care should be an urgent priority. That's the conclusion of a study published on World Diabetes Day in the European Journal of Preventive Cardiology, a journal of the European Society of Cardiology (ESC).1

"The most striking result of our study was that the vast majority of patients (93%) had a high or very high risk of fatal events within a decade. Half of patients in the very high-risk group had no history of heart disease, meaning they would not be receiving medications to prevent heart attacks and strokes," said study author Dr. Manel Mata-Cases, a general practitioner for the Catalan Institute of Health in Sant Adrià de Besòs.2

"As far as we know, this study in nearly 375,000 people from a well-validated population-based database illustrates the situation in the Mediterranean for the first time. Traditionally, cardiovascular risk in the region has been lower than in central and northern Europe or the US; therefore, our results should generate concern and a call for action to prevent heart attacks and strokes in people with type 2 diabetes managed in primary care," he added.

This was a cross-sectional study that used the Information System for the Development of Research in Primary Care (SIDIAP) database, which includes 74% of the total population in Catalonia, Spain. The SIDIAP database contains anonymous, longitudinal patient information extracted from the electronic medical record system (e-CAP) used by all primary health providers in Catalonia.

The study population consisted of 373,185 people aged 18 and over with a diagnosis of type 2 diabetes by 31 December 2016. The average age was 70.1 years and 45.2% were female. Some 72% had high blood pressure, 45% were obese, 60% had high serum cholesterol, and 14% were current smokers.

The investigators calculated the likelihood of each participant having a fatal heart attack or stroke within 10 years using categories in the ESC guidelines on diabetes and cardiovascular disease.3 The three categories are: very high risk (above 10%), high risk (between 5% and 10%), and moderate risk (below 5%).

To be classified as very high risk, patients must have established cardiovascular disease (e.g. prior heart attack or stroke), or other conditions which threaten their health such as kidney impairment, or at least three cardiovascular risk factors (older age, high blood pressure, high serum cholesterol, smoking, obesity).4

Over half of the participants (53.4%) were at very high risk of fatal events. This observation was more frequent in men (55.6%) than in women (50.7%). Some 39.6% were classified as high risk and just 7% had moderate risk of dying from a heart attack or stroke within 10 years.

Dr. Mata-Cases concluded: "These findings in a primary care setting should fuel the implementation of integrated care. Healthy behaviours are the cornerstone of preventing cardiovascular disease and need to be combined with control of blood glucose, serum cholesterol, and blood pressure. GPs and nurses should agree treatment objectives with patients considering their characteristics and preferences."

Lifestyle advice for patients with diabetes

Quit smoking.

Reduce calorie intake to lower excessive body weight.

Adopt a Mediterranean diet supplemented with olive oil and/or nuts.

Avoid alcohol.

Do moderate-to-vigorous physical activity for at least 150 minutes per week.

Credit: 
European Society of Cardiology

The future's uncertain - but noradrenaline can help us adapt

A brain chemical called noradrenaline is responsible for our responses to uncertain situations - helping us to learn quickly and adapt our behaviour, a new study has found.

The COVID-19 pandemic has plunged us all into a state of uncertainty. In a rapidly changing situation where it is hard to know what will happen next, making decisions can be difficult. Researchers at the University of Cambridge and University College London created a simplistic model of this uncertain situation in the lab, to understand how our brain responds.

They found that when situations seem stable, we tend to rely on our on previous experiences to help us anticipate what will happen in the future. But when the world is volatile, our brain can let go of these expectations and allow rapid learning. The balance between the two approaches is moderated by the brain chemical noradrenaline. The study is published today in the journal Current Biology.

"Adapting to uncertain situations helps us to survive. When something unexpected happens, we have to decide whether it's a one-off and ignore it, or whether it's going to keep happening - in which case we might benefit by doing things differently," said Dr Rebecca Lawson, a researcher in the University of Cambridge's Department of Psychology and lead author of the study.

The study tested the effects of Propranolol - a drug used to reduce anxiety and blood pressure - on how people responded to stable situations and to changeable ones. Propranolol blocks the action of noradrenaline.

Participants in the experiment - who were not suffering with anxiety - heard a sound and were then shown an image of either a house of a face. They quickly learned to predict the image they would see depending on the sound they heard before it appeared. The association between particular sounds and images was then changed at random intervals, increasing uncertainty and requiring participants to quickly learn new associations.

The reaction times of participants who received a placebo drug slowed down as the associations became more unexpected. Those who received Propranolol relied on the sound to a greater extent when uncertainty was high. This suggests that the drug makes people more likely to rely on their expectations, based on prior experience, in the face of uncertainty - which could be how it works to reduce feelings of anxiety.

Using a computational model, the researchers showed that the Propranolol group were slower than the placebo group at learning to use new information to adjust their expectations of what might come next, when a situation is very uncertain.

"We found that a brain chemical called noradrenaline plays a role in our inability to predict the future when the state of the world is volatile," said Lawson.

When a situation is stable - represented in the experiment by a fixed link between sounds and images - our past experiences can be relied upon as a good guide to what will happen next. But when a situation is changing, we need to be more receptive to new information to try and work out what is happening and how to respond.

"In the face of uncertainty, people taking the anti-anxiety drug Propranolol showed an increased reliance on past experience to inform their behaviour - they were less influenced by changes in their environment that contradicted that experience," said Lawson.

Difficulty in balancing expectations against new information is thought to underlie many conditions including autism and anxiety. The team plans to extend their research to try and understand how people with these conditions learn under uncertainty. In the longer term, this could help those with autism and anxiety to recognise the source of their anxiety and manage it better.

Credit: 
University of Cambridge