Tech

People who feel dizzy when they stand up may have higher risk of dementia

MINNEAPOLIS - Some people who feel dizzy or lightheaded when they stand up may have an increased risk of developing dementia years later, according to a new study published in Neurology®, the medical journal of the American Academy of Neurology. The condition, called orthostatic hypotension, occurs when people experience a sudden drop in blood pressure when they stand up.

The study found the link with dementia only in people who have a drop in their systolic blood pressure, not in people with only a drop in their diastolic blood pressure or their blood pressure overall.

Systolic is the first, or top, number in a blood pressure reading and systolic orthostatic hypotension was defined as a drop of at least 15 mmHg after standing from a sitting position.

"People's blood pressure when they move from sitting to standing should be monitored," said study author Laure Rouch, Pharm.D., Ph.D., of the University of California, San Francisco. "It's possible that controlling these blood pressure drops could be a promising way to help preserve people's thinking and memory skills as they age."

The study involved 2,131 people who were an average age of 73 and did not have dementia when they enrolled. Their blood pressure readings were taken at the start of the study and then one, three and five years later. A total of 15% had orthostatic hypotension, 9% had systolic orthostatic hypotension and 6% had diastolic orthostatic hypotension.

Over the next 12 years, the participants were evaluated to see if anyone developed dementia. A total of 462 people, or 22%, did develop the disease.

The people with systolic orthostatic hypotension were nearly 40% more likely to develop dementia than those who did not have the condition. Fifty of the 192 with systolic orthostatic hypotension, or 26%, developed dementia, compared to 412 of the 1,939 people without it, or 21%. When researchers adjusted for other factors that could affect dementia risk, such as diabetes, smoking and alcohol use, those with systolic orthostatic hypotension were 37% more likely to develop dementia.

The researchers also found that people whose sitting-to-standing systolic blood pressure readings changed the most from visit to visit were more likely to develop dementia years later than people whose readings were more stable.

The people were divided into three groups based on how much their readings changed over time. A total of 24% of people in the group with the most fluctuation in systolic readings later developed dementia, compared to 19% of the people in the group with the least fluctuation. When researchers adjusted for other factors affecting dementia risk, those in the highest group were 35% more likely to develop dementia than those in the lowest group.

Rouch noted that the study is observational and does not show cause and effect. It only shows an association between the blood pressure readings and the development of dementia. Another limitation of the study was that the diagnosis of dementia was made without distinction between Alzheimer's disease and vascular dementia.

Credit: 
American Academy of Neurology

Study: Most Americans don't have enough assets to withstand 3 months without income

CORVALLIS, Ore. -- A new study from Oregon State University found that 77% of low- to moderate-income American households fall below the asset poverty threshold, meaning that if their income were cut off they would not have the financial assets to maintain at least poverty-level status for three months.

The study compared asset poverty rates in the U.S. and Canada. Canada's asset poverty rate has improved over the past 20 years while the U.S. rate has worsened, but still, 62% of low- to moderate-income Canadians also fall below the asset poverty threshold.

The implications of these findings have become starkly apparent during the COVID-19 pandemic, said David Rothwell, lead author on the study and an associate professor in OSU's College of Public Health and Human Sciences.

"The fact that the U.S. safety net is so connected to work, and then you have this huge shock to employment, you have a system that's not prepared to handle such a big change to the employment system ... It results concretely in family stress and strain, and then that strain and stress relates to negative outcomes for children and families," Rothwell said.

The study, published last week in the journal Social Policy Administration, looked at financial assets such as stocks, bonds and mutual funds, rather than real assets like houses and property, because financial assets are easier to cash in and use in an emergency. Existing research has found that U.S. wealth inequality is more pronounced that income inequality.

Researchers used data from nationally representative financial surveys in Canada and the U.S. from 1998 through 2016, looking at low- to moderate-income households, defined as those in the bottom 50% of income distribution in each country, headed by working age adults age 25-54.

Rothwell and co-authors Leanne Giordono from OSU and Jennifer Robson from Carleton University in Ontario, Canada, were investigating how asset poverty changed over time in the two countries and how that change was affected by changes in transfer share -- the portion of household income that comes from government assistance. They chose the U.S. and Canada because of their close geographic proximity and similar legal traditions but significantly different welfare policies.

In 1998, Canada's asset poverty rate among low- to moderate-income households was 74%, compared with 67% in the U.S. The two rates were nearly identical in 2005, then Canada's kept falling and the U.S. rate kept rising, arriving at 62% and 77% in 2016.

Canada spends twice what the U.S. does on financial assistance for families, and much of it is spent in cash benefits, rather than in-kind benefits like Supplemental Nutrition Assistance Programs (SNAP, formerly food stamps) in the U.S. In 2016, 96% of low- to moderate-income Canadian households received some transfer income from the government. In the U.S., that number was 41%.

For the most part, results showed that more generous welfare policies were associated with greater rates of asset poverty in Canada, Rothwell said. There, as the government reduced the amount of public assistance families received as a proportion of their income over time, asset poverty improved.

However, he said, this relationship between welfare generosity and asset poverty should be interpreted as correlational, not causal, and the topic warrants further study. Because the levels of public assistance are greater in Canada than the U.S., it's hard to extend results from one country to the other, but when controlling for demographic characteristics, researchers found that decreasing transfer share has no impact on the risk of asset poverty in the U.S.

"What stands out there is, so few American families receive any type of transfers at all, compared to other countries, and small adjustments to an already minimal safety net was not related to asset poverty in this study," Rothwell said. In contrast, Canadian families receive a child benefit, a monthly cash payment of several hundred dollars to help with the cost of raising a child.

Many safety net programs, including Medicaid and SNAP, also disincentivize saving because they impose asset limits on people seeking assistance. Rothwell calls these a "poverty trap."

"If you have someone who's low-income and they are working hard trying to save money but you're telling them that they're going to lose benefits if they save over some given threshold, that's a disincentive to accumulate wealth," he said.

Rothwell notes that asset poverty rates are much higher among people of color, due to decades of discriminatory laws and policies that prevented Black people, in particular, from buying and owning homes or securing well-paying jobs.

"This is the story of COVID, as I see it -- it's just exposing these existing inequalities, and the people who are most vulnerable going into the crisis are magnified in their vulnerability getting through it," Rothwell said.

A study coming out later this year from the same research team will look specifically at racial and ethnic asset disparities and how they impact people's health, he said.

Credit: 
Oregon State University

Chemists create the brightest-ever fluorescent materials

image: This image shows glowing 3D-printed gyroids made with bright SMILES materials.

Image: 
Amar Flood

By formulating positively charged fluorescent dyes into a new class of materials called small-molecule ionic isolation lattices (SMILES), a compound's brilliant glow can be seamlessly transferred to a solid, crystalline state, researchers report August 6 in the journal Chem. The advance overcomes a long-standing barrier to developing fluorescent solids, resulting in the brightest known materials in existence.

"These materials have potential applications in any technology that needs bright fluorescence or calls for designing optical properties, including solar energy harvesting, bioimaging, and lasers," says Amar Flood, a chemist at Indiana University and co-senior author on the study along with Bo Laursen of the University of Copenhagen.

"Beyond these, there are interesting applications that include upconverting light to capture more of the solar spectrum in solar cells, light-switchable materials used for information storage and photochromic glass, and circularly polarized luminescence that may be used in 3D display technology," Flood says.

While there are currently more than 100,000 different fluorescent dyes available, almost none of these can be mixed and matched in predictable ways to create solid optical materials. Dyes tend to undergo "quenching" when they enter a solid state due to how they behave when packed close together, decreasing the intensity of their fluorescence to produce a more subdued glow.

"The problem of quenching and inter-dye coupling emerges when the dyes stand shoulder-to-shoulder inside solids," says Flood. "They cannot help but 'touch' each other. Like young children sitting at story time, they interfere with each other and stop behaving as individuals."

To overcome this problem, Flood and colleagues mixed a colored dye with a colorless solution of cyanostar, a star-shaped macrocycle molecule that prevents the fluorescent molecules from interacting as the mixture solidified, keeping their optical properties intact. As the mixture became a solid, SMILES formed, which the researchers then grew into crystals, precipitated into dry powders, and finally spun into a thin film or incorporated directly into polymers. Since the cyanostar macrocycles form building blocks that generate a lattice-like checkerboard, the researchers could simply plug a dye into the lattice and, without any further adjustments, the structure would take on its color and appearance.

While previous research had already developed an approach to spacing the dyes apart using macrocycle molecules, it relied on colored macrocycles to do the job. Flood and colleagues found that colorless macrocycles were key.

"Some people think that colorless macrocycles are unattractive, but they allowed the isolation lattice to fully express the bright fluorescence of the dyes unencumbered by the colors of the macrocycles," says Flood.

Next, the researchers plan to explore the properties of fluorescent materials formed using this novel technique, enabling them to work with dye makers in the future to realize the materials' full potential in a variety of different applications.

"These materials are totally new, so we do not know which of their innate properties are actually going to offer superior functionality," says Flood. "We also do not know the materials' limits. So, we will develop a fundamental understanding of how they work, providing a robust set of design rules for making new properties. This is critical for putting these materials into the hands of others--we want to pursue crowd sourcing and to work with others in this effort."

Credit: 
Cell Press

New fossil discovery shows how ancient 'hell ants' hunted with headgear

image: Researchers discover a worker of the hell ant Ceratomyrmex ellenbergeri grasping a nymph of Caputoraptor elegans (Alienoptera) preserved in amber dated to ~99 Ma.

Image: 
NJIT, Chinese Academy of Sciences and University of Rennes, France

In findings published Aug. 6 in the journal Current Biology, researchers from New Jersey Institute of Technology (NJIT), Chinese Academy of Sciences and University of Rennes in France have unveiled a stunning 99-million-year-old fossil pristinely preserving an enigmatic insect predator from the Cretaceous Period -- a 'hell ant' (haidomyrmecine) -- as it embraced its unsuspecting final victim, an extinct relative of the cockroach known as Caputoraptor elegans.

The ancient encounter, locked in amber recovered from Myanmar, offers a detailed glimpse at a newly identified prehistoric ant species Ceratomyrmex ellenbergeri, and presents some of the first direct evidence showing how it and other hell ants once used their killer features -- snapping their bizarre, but deadly, scythe-like mandibles in a vertical motion to pin prey against their horn-like appendages.

Researchers say the rare fossil demonstrating the hell ant's feeding mode offers a possible evolutionary explanation for its unusual morphology and highlights a key difference between some of the earliest ant relatives and their modern counterparts, which today uniformly feature mouthparts that grasp by moving together laterally. The hell ant lineage, along with their striking predatory traits, are suspected to have vanished along with many other early ant groups during periods of ecological change around the Cretaceous-Paleogene extinction event 65 million years ago.

"Fossilized behavior is exceedingly rare, predation especially so. As paleontologists, we speculate about the function of ancient adaptations using available evidence, but to see an extinct predator caught in the act of capturing its prey is invaluable," said Phillip Barden, assistant professor at NJIT's Department of Biological Sciences and lead author of the study. "This fossilized predation confirms our hypothesis for how hell ant mouthparts worked ... The only way for prey to be captured in such an arrangement is for the ant mouthparts to move up and downward in a direction unlike that of all living ants and nearly all insects."

"Since the first hell ant was unearthed about a hundred years ago, it's been a mystery as to why these extinct animals are so distinct from the ants we have today," Barden added. "This fossil reveals the mechanism behind what we might call an 'evolutionary experiment,' and although we see numerous such experiments in the fossil record, we often don't have a clear picture of the evolutionary pathway that led to them."

Driving Diversity of Hell Ants & Their Headgear

Barden's team suggests that adaptations for prey-capture likely explain the rich diversity of mandibles and horns observed in the 16 species of hell ants identified to date. Some taxa with unarmed, elongate horns such as Ceratomyrmex apparently grasped prey externally, while other hell ants such as Linguamyrmex vladi, or "Vlad the Impaler" discovered by Barden and colleagues in 2017, was thought to have used a metal-reinforced horn on its head to impale prey -- a trait potentially used to feed on the internal liquid (hemolymph) of insects.

Barden says the earliest hell ant ancestors would have first gained the ability to move their mouthparts vertically. This, in turn, would functionally integrate the mouthparts and head in a way that was unique to this extinct lineage.

"Integration is a powerful shaping force in evolutionary biology ... when anatomical parts function together for the first time, this opens up new evolutionary trajectories as the two features evolve in concert," explained Barden. "The consequences of this innovation in mouthpart movement with the hell ants are remarkable. While no modern ants have horns of any kind, some species of hell ant possess horns coated with serrated teeth, and others like Vlad are suspected to have reinforced its horn with metal to prevent its own bite from impaling itself."

To explore further, the researchers compared the head and mouthpart morphology of Ceratomyrmex and several other hell ant species (such as head, horn and mandible size) with similar datasets of living and fossil ant species. The team also conducted a phylogenetic analysis to reconstruct evolutionary relationships among both Cretaceous and modern ants. The team's analyses confirmed that hell ants belong to one of the earliest branches of the ant evolutionary tree and are each other's closest relatives. Moreover, the relationship between mandible and head morphology is unique in hell ants compared to living lineages as a result of their specialized prey-capture behavior. The analyses also demonstrated that elongated horns evolved twice in hell ants.

While the fossil has finally provided Barden's lab with firmer answers as to how this long-lost class of ant predators functioned and found success for nearly 20 million years, questions persist such as what led these and other lineages to go extinct while modern ants flourished into the ubiquitous insects we know today. Barden's team is now seeking to describe species from new fossil deposits to learn more about how extinction impacts groups differentially.

"Over 99% of all species that have ever lived have gone extinct," said Barden. "As our planet undergoes its sixth mass extinction event, it's important that we work to understand extinct diversity and what might allow certain lineages to persist while others drop out. I think fossil insects are a reminder that even something as ubiquitous and familiar as ants have undergone extinction."

Credit: 
New Jersey Institute of Technology

The bouncer in the brain

image: How do you keep orientation in a complex environment, like the city of Vienna? You can thank your brain's "global positioning system" (GPS), the hippocampus, for this sense of orientation. To further understand its functions, scientists at the Institute of Science and Technology Austria (IST Austria) analyzed single neurons of this GPS in mice. They discovered that so-called granule cells filter and sharpen spatial information. The researchers recently published their findings in Neuron.

Image: 
Rieger / IST Austria

The hippocampus is a region within the brain that contains many neurons that help us to navigate in space. This leads to the nickname of this area: the GPS of the brain. The higher areas of the cortex send information packages to the hippocampus to generate location signals. However, not all packages contain relevant information. Therefore, the hippocampus needs to have a bouncer in place to select incoming signals. Such a gatekeeper could be the granule cell, a type of neuron situated at the entrance of the hippocampal circuit.

Identifying the correct cells

IST Austria Professor Peter Jonas, Xiaomin Zhang, and Alois Schlögl started to examine neuronal signals in granule cells. However, the main problem was cell identification. In the past, experts could not guarantee that they correctly identified the cells. "Since this region is densely packed with various types of neurons, it is technically challenging to identify granule cells, the cells we were interested in," says Xiaomin Zhang, the first author on the paper. This makes it very difficult to distinguish between the activity of granule cells from that of other types of neurons located in the same region. Furthermore, granule cells typically show very sparse activity despite a vast amount of them. Thus, other cell types with higher activity levels could dominate the picture.

Gatekeepers of the hippocampus

To record the incoming and outgoing signals of the granule cells, the scientists developed a novel recording technique and machine learning algorithm to decode these signals. To unequivocally identify the neurons, cells were filled with a tracer during recording. In total, they recorded from almost a hundred granule cells, generating a large data set that describes the activity of this important type of cell. They found that a majority of neurons receive spatial information. However, only a minority of neurons relays this spatial information to the rest of the hippocampus. Thus, granule cells indeed appear to operate as gatekeepers.

Spatial information processing

However, granule cells not only select information but also appear to be involved in information processing. The team found that the input of the granule cells is broad, but the output is much more selective. Upstream cortical areas neurons are often grid cells that generate activity in multiple locations of the environment. In contrast, downstream hippocampal regions neurons are typically place cells, which fire only at a single location. The new study suggests that granule cells participate in this conversion. "In simplified terms, we can think of the granule cell as a unit that translates one neuronal language into another," Jonas explains.

Saving computation power for the future

The majority of granule cells receive spatial information, but only 5% generate spatial output. Xiaomin Zhang explains: "Especially neurons with a more developed structure were active, whereas neurons with less mature structure remained silent." What could be the functional significance of such a unique design, in which a huge fraction of cells is not directly used for information processing? The scientists suggested that the hippocampus reserves most granule cells for future conversion and storage processes.

The new work highlights the power of single-cell recording techniques. "Our study provides information about the inner workings of the brain's GPS and the underlying single-neuron computations," summarizes Professor Peter Jonas.

Credit: 
Institute of Science and Technology Austria

Tasmanian devil research offers new insights for tackling cancer in humans

PULLMAN, Wash. - A rare, transmissible tumor has brought the iconic Tasmanian devil to the brink of extinction, but new research by scientists at Washington State University and the Fred Hutchinson Cancer Research Center in Seattle indicates hope for the animals' survival and possibly new treatment for human cancers.

The study, published in Genetics on Aug. 1, found a single genetic mutation that leads to reduced growth of a transmissible cancer in Tasmanian devils in the wild.

"This gene is implicated in human prostate and colon cancers," said Andrew Storfer, professor of biological sciences at WSU. "While the findings hold the most immediate promise to help save the world's few remaining Tasmanian devils, these results could also someday translate to human health."

The research team, led by Storfer and Mark Margres, now a postdoctoral fellow at Harvard University, studied the genomes of cases of devil facial tumor disease, or DFTD, that regressed spontaneously -- that is, the cancer began disappearing on its own.

They were surprised to find the mutation contributing to tumor regression doesn't change the gene function but instead, turns on a gene that slows cell growth in the tumor. At least, it behaves that way in the lab.

Current human cancer therapies focus on removing every trace of a tumor, often through toxic or debilitating treatments, said David Hockenbery, a cancer biologist at Fred Hutch who contributed to the study.

"If there were ways that tumors could be tricked into regressing without having to administer cytotoxic drugs or deforming surgeries, it would be a major advance," he said.

While infections cause up to 20 percent of all human cancers - such as gastric cancer from Helicobacter pylori and cervical cancer from human papillomavirus - for Tasmanian devils, the cancer is the infection.

DFTD spreads between the animals when they bite each other during common social behaviors. Since the mid-1990s, the disease has decimated the natural population of the carnivorous marsupials, which are now found only on the island state of Tasmania, off the southeastern coast of Australia.

Storfer's lab leads a National Institutes of Health-funded team of researchers from the U.S. and Australia to improve conservation efforts for Tasmanian devils and increase understanding of the co-evolution of the tumor and its host.

Though ferocious with each other, Tasmanian devils take mild handling by people without much fuss, making it easy for investigators to humanely capture the animals, collect tissue samples and tag them for monitoring before release back into the wild.

As the researchers work to save the devils, they also have an unprecedented opportunity to watch tumors naturally evolve and sometime regress without drugs or surgery.

"Although this disease is largely fatal, we're seeing tumors just disappear from an increasing number of individual animals," Storfer said.

The team is looking at the effects of other promising mutations in regressed tumors as well.

"We hope to learn something that could be applied to understanding and possibly treating a number of human cancers in the future," Storfer said.

Credit: 
Washington State University

NTU develops peptide that makes drug-resistant bacteria sensitive to antibiotics again

image: Scientists at NTU have developed a synthetic antimicrobial peptide that makes drug-resistant bacteria sensitive to antibiotics again. On its own, the peptide can also kill bacteria that have grown resistant to antibiotics. (L-R) NTU Prof Mary Chan; Dr Adeline Yong, SCELSE research fellow; NTU Assoc Prof Kimberly Kline.

Image: 
NTU Singapore

Scientists at Nanyang Technological University, Singapore (NTU Singapore) have developed a synthetic peptide that can make multidrug-resistant bacteria sensitive to antibiotics again when used together with traditional antibiotics, offering hope for the prospect of a combination treatment strategy to tackle certain antibiotic-tolerant infections.

On its own, the synthetic antimicrobial peptide can also kill bacteria that have grown resistant to antibiotics.

Every year, an estimated 700,000 people globally die of antibiotic-resistant diseases, according to the World Health Organisation. In the absence of new therapeutics, infections caused by resistant superbugs could kill an additional 10 million people each year worldwide by 2050, surpassing cancer[1]. Antibiotic resistance arises in bacteria when they can recognise and prevent drugs that would otherwise kill them, from passing through their cell wall.

This threat is accelerated by the developing COVID-19 pandemic, with patients admitted to hospitals often receiving antibiotics to keep secondary bacterial infections in check, amplifying the opportunity for resistant pathogens to emerge and spread[2].

The NTU Singapore team, led by Associate Professor Kimberly Kline and Professor Mary Chan, developed an antimicrobial peptide known as CSM5-K5 comprising repeated units of chitosan, a sugar found in crustacean shells that bears structural resemblance to the bacterial cell wall, and repeated units of the amino acid lysine.

The scientists believe that chitosan's structural similarity to the bacterial cell wall helps the peptide interact with and embed itself in it, causing defects in the wall and membrane that eventually kill the bacteria.

The team tested the peptide on biofilms, which are slimy coats of bacteria that can cling onto surfaces such as living tissues or medical devices in hospitals, and which are difficult for traditional antibiotics to penetrate.

In both preformed biofilms in the lab and biofilms formed on wounds in mice, the NTU-developed peptide killed at least 90 per cent of the bacteria strains in four to five hours.

In separate experiments, when CSM5-K5 was used with antibiotics that the bacteria are otherwise resistant to, more bacteria was killed off as compared to when CSM5-K5 was used alone, suggesting that the peptide rendered the bacteria susceptible to antibiotics. The amount of antibiotics used in this combination therapy was also at a concentration lower than what is commonly prescribed.

The findings were published in the scientific journal ACS Infectious Diseases in May.

Assoc Prof Kimberly Kline, a Principal Investigator at the Singapore Centre for Environmental Life Sciences Engineering (SCELSE) at NTU, said: "Our findings show that our antimicrobial peptide is effective whether used alone or in combination with conventional antibiotics to fight multidrug-resistant bacteria. Its potency increases when used with antibiotics, restoring the bacteria's sensitivity to drugs again. More importantly, we found that the bacteria we tested developed little to no resistance against our peptide, making it an effective and feasible addition to antibiotics as a viable combination treatment strategy as the world grapples with rising antibiotic resistance."

Prof Mary Chan, director of NTU's Centre of Antimicrobial Bioengineering, said: "While efforts are focussed on dealing with the COVID-19 pandemic, we should also remember that antibiotic resistance continues to be a growing problem, where secondary bacterial infections that develop in patients could complicate matters, posing a threat in the healthcare settings. For instance, viral respiratory infections could allow bacteria to enter the lungs more easily, leading to bacterial pneumonia, which is commonly associated with COVID-19."

How the antimicrobial peptide works

Antimicrobial peptides, which carry a positive electric charge, typically work by binding to the negatively-charged bacterial membranes, disrupting the membrane and causing the bacteria to die eventually. The more positively charged a peptide is, the more efficient it is in binding to bacteria and thus killing them.

However, the peptide's toxicity to the host also increases in line with the peptide's positive charge - it damages the host organism's cells as it kills bacteria. As a result, engineered antimicrobial peptides to date have met with limited success, said Assoc Prof Kline, who is also from the NTU School of Biological Sciences.

The peptide designed by the NTU team, called CSM5-K5, is able to cluster together to form nanoparticles when it is applied to bacteria biofilms. This clustering results in a more concentrated disruptive effect on the bacterial cell wall when compared to the activity of single chains of peptides, meaning it has high antibacterial activity but without causing undue damage to healthy cells (See Image 1 in Note to Editors).

To examine CSM5-K5's efficacy on its own, the NTU scientists developed separate biofilms comprising methicillin-resistant Staphylococcus aureus, commonly known as the MRSA superbug; a highly virulent multidrug-resistant strain of Escherichia coli (MDR E. Coli); and vancomycin-resistant Enterococcus faecalis (VRE). MRSA and VRE are classified as serious threats by the US Centers for Disease Control and Prevention[3].

In lab experiments, CSM5-K5 killed more than 99 per cent of the biofilm bacteria after four hours of treatment. In infected wounds on mice, the NTU-developed antimicrobial peptide killed more than 90 per cent of the bacteria.

When CSM5-K5 was used with conventional antibiotics, the NTU team found that the combination approach led to a further reduction in the bacteria in both lab-formed biofilms and infected wounds in mice as compared to when only CSM5-K5 was used, suggesting that the antimicrobial peptide made the bacteria sensitive to the drugs they would otherwise be resistant to.

More importantly, the NTU team found that the three strains of bacteria studied (MRSA, VRE and MDR E. coli) developed little to no resistance against CSM5-K5. While MRSA developed low-level resistance against CSM5-K5, this made MRSA more sensitive to the drug it is otherwise resistant to.

Prof Chan said: "Developing new drugs alone is no longer sufficient to fight difficult-to-treat bacterial infections, as bacteria continue to evolve and outsmart antibiotics/ It is important to look at innovative ways to tackle difficult-to-treat bacterial infections associated with antibiotic resistance and biofilms, such as tackling the bacteria's defence mechanisms. A more effective and economic method to fight bacteria is through a combination therapy approach like ours."

The next step forward for the team is to explore how such a combination therapy approach can be used for rare diseases or for wound dressing.

Credit: 
Nanyang Technological University

A closer look at water-splitting's solar fuel potential

image: Francesca Toma (right) and Johanna Eichhorn developed a special technique using an atomic force microscope at Berkeley Lab's JCAP laboratory to capture images of thin-film bismuth vanadate at the nanoscale to understand how a material's properties can affect its performance in an artificial photosynthesis device.

Image: 
Marilyn Sargent/ Berkeley Lab

In the fight against climate change, scientists have searched for ways to replace fossil fuels with carbon-free alternatives such as hydrogen fuel.

A device known as a photoelectrical chemical cell (PEC) has the potential to produce hydrogen fuel through artificial photosynthesis, an emerging renewable energy technology that uses energy from sunlight to drive chemical reactions such as splitting water into hydrogen and oxygen.

The key to a PEC's success lies not only in how well its photoelectrode reacts with light to produce hydrogen, but also oxygen. Few materials can do this well, and according to theory, an inorganic material called bismuth vanadate (BiVO4) is a good candidate.

Yet this technology is still young, and researchers in the field have struggled to make a BiVO4 photoelectrode that lives up to its potential in a PEC device. Now, as reported in the journal Small, a research team led by scientists at the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and the Joint Center for Artificial Photosynthesis (JCAP), a DOE Energy Innovation Hub, have gained important new insight into what might be happening at the nanoscale (billionths of a meter) to hold BiVO4 back.

"When you make a material, such as an inorganic material like bismuth vanadate, you might assume, just by looking at it with the naked eye, that the material is homogeneous and uniform throughout," said senior author Francesca Toma, a staff scientist at JCAP in Berkeley Lab's Chemical Sciences Division. "But when you can see details in a material at the nanoscale, suddenly what you assumed was homogeneous is actually heterogeneous - with an ensemble of different properties and chemical compositions. And if you want to improve a photoelectrode material's efficiency, you need to know more about what's happening at the nanoscale."

X-rays and simulations bring a clearer picture into focus

In a previous study supported by the Laboratory Directed Research and Development program, Toma and lead author Johanna Eichhorn developed a special technique using an atomic force microscope at Berkeley Lab's JCAP laboratory to capture images of thin-film bismuth vanadate at the nanoscale to understand how a material's properties can affect its performance in an artificial photosynthesis device. (Eichhorn, who is currently at the Walter Schottky Institute of the Technical University of Munich in Germany was a researcher in Berkeley Lab's Chemical Sciences Division at the time of the study.)

The current study builds on that pioneering work by using a scanning transmission X-ray microscope (STXM) at Berkeley Lab's Advanced Light Source (ALS) (https://als.lbl.gov/), a synchrotron user facility, to map out changes in a thin-film semiconducting material made of molybdenum bismuth vanadate (Mo-BiVO4).

The researchers used bismuth vanadate as a case example of a photoelectrode because the material can absorb light in the visible range in the solar spectrum, and when combined with a catalyst, its physical properties allow it to make oxygen in the water-splitting reaction. Bismuth vanadate is one of the few materials that can do this, and in this case, the addition of a small quantity of molybdenum to BiVO4 somehow improves its performance, Toma explained.

When water is split into H2 and O2, hydrogen-hydrogen and oxygen-oxygen bonds need to form. But if any step in water-splitting is out of sync, unwanted reactions will happen, which could lead to corrosion. "And if you want to scale up a material into a commercial water-splitting device, no one wants something that degrades. So we wanted to develop a technique that maps out which regions at the nanoscale are the best at making oxygen," Toma explained.

Working with ALS staff scientist David Shapiro, Toma and her team used STXM to take high-resolution nanoscale measurements of grains in a thin film of Mo-BiVO4 as the material degraded in response to the water-splitting reaction triggered by light and the electrolyte.

"Chemical heterogeneity at the nanoscale in a material can often lead to interesting and useful properties, and few microscopy techniques can probe the molecular structure of a material at this scale," Shapiro said. "The STXM instruments at the Advanced Light Source are very sensitive probes that can nondestructively quantify this heterogeneity at high spatial resolution and can therefore provide a deeper understanding of these properties."

David Prendergast, interim division director of the Molecular Foundry, and Sebastian Reyes-Lillo, a former postdoctoral researcher at the Foundry, helped the team understand how Mo-BiVO4 responds to light by developing computational tools to analyze each molecule's spectral "fingerprint." Reyes-Lillo is currently a professor at Andres Bello University in Chile and a Molecular Foundry user. The Molecular Foundry is a Nanoscale Science Research Center national user facility.

"Prendergast's technique is really powerful," Toma said. "Often when you have complex heterogeneous materials made of different atoms, the experimental data you get is not easy to understand. This approach tells you how to interpret those data. And if we have a better understanding of the data, we can create better strategies for making Mo-BiVO4 photoelectrodes less vulnerable to corrosion during water-splitting."

Reyes-Lillo added that Toma's use of this technique and the work at JCAP enabled a deeper understanding of Mo-BiVO4 that would otherwise not be possible. "The approach reveals element-specific chemical fingerprints of a material's local electronic structure, making it especially suited for the study of phenomena at the nanoscale. Our study represents a step toward improving the performance of semiconducting BiVO4-based materials for solar fuel technologies," he said.

Next steps

The researchers next plan to further develop the technique by taking STXM images while the material is operating so that they can understand how the material changes chemically as a photoelectrode in a model PEC system.

"I'm very proud of this work. We need to find alternative solutions to fossil fuels, and we need renewable alternatives. Even if this technology isn't ready for the marketplace tomorrow, our technique - along with the powerful instruments available to users at the Advanced Light Source and the Molecular Foundry - will open up new routes for renewable energy technologies to make a difference."

Credit: 
DOE/Lawrence Berkeley National Laboratory

Gut bacteria in people with Huntington's disease may be a potential drug target

A world first clinical study of the gut microbiome in people with Huntington's disease (HD) has found that it is not just a disease of the brain, but also of the body.

The study, led by Monash University's Turner Institute for Brain and Mental Health, with collaboration from the Florey Institute for Neurosciences found evidence of gut dysbiosis (altered bacteria in the gastrointestinal tract) in people with HD, with some of the gut measures associated with disease symptoms, such as impaired movements and thinking.

The findings, published in Brain Communications, raise interesting questions regarding the role of the gut in Huntington's Disease, and its potential as a target for future therapeutic intervention, or for tracking disease progression.

The lead researchers, Neuropsychology Doctoral Candidate Cory Wasser and Professor Julie Stout, Director of Monash University's Clinical Cognitive Neuroscience Laboratory, used fecal samples to investigate whether the gut microbiome in people with HD differs to those without the HD gene.

The study included 42 participants with the HD gene, including 19 people with HD, 23 people with the HD gene but not yet showing HD symptoms, and 36 healthy participants who did not carry the gene mutation.

According to Professor Stout, "It is also possible that the changes in these trillions of gut bacteria - which outnumber the trillion or so human cells in each person's body - which are known to 'talk to the brain', could also affect symptoms of HD such as depression and dementia."

In people with HD, the researchers found major shifts at the level of bacterial families, altering the potential of the gut for sending signals to the brain and other organs.

These findings may also mean that changing gut bacteria may be a cause or precursor to some of the more debilitating symptoms associated with HD, according to the researchers.

"These results raise the tantalising proposition of whether the gut may be a potential target for future therapeutic intervention to improve outcomes in Huntington's disease and other neurodegenerative diseases," Professor Stout said.

Huntington's disease is a debilitating genetic neurological condition which gradually affects a person's movements, emotional and cognitive function. Each offspring of a parent with the HD gene has a 50 per cent chance of inheriting the genetic mutation causing the disease.

There is no cure and once symptoms appear, life expectancy reduces by 10-25 years, with latter stages of the disease severely impacting quality of life.

In people with HD, motor symptoms become debilitating, cognitive decline eventually progresses to dementia, and depression is estimated to be five to 10 times more common in HD than in the general population.

Read the full paper in Brain Communications titled: Gut dysbiosis in Huntington's disease: associations between gut microbiota, cognitive performance and clinical outcomes.

Credit: 
Monash University

Researchers propose strategy to evaluate tumor photothermal therapy in real-time

image: Illustration of the fluorescence "On" process.

Image: 
WANG Yanfang et al.

Photothermal therapy (PTT) is a promising alternative method for cancer treatment due to advantages of non-invasiveness, precise temporal and spatial control, strong specificity and high tumor destruction efficiency.

At present, the clinical evaluation of cancer treatment mainly relies on cytology, histopathology and imaging. Meanwhile, tumor therapy and its therapeutic efficiency evaluation are conducted separately.

Recently, a research group led by Prof. LIANG Gaolin from University of Science and Technology of China (USTC) of Chinese Academy of Science, collaborating with Dr. WANG Longsheng from the Second Affiliated Hospital of Anhui Medical University, reported an "intelligent" strategy of using organic nanoparticles to evaluate PTT efficiency on tumor in real time.

The study was published online in ACS Nano on July 27.

Via a CBT-Cys click condensation reaction, the researchers designed a small molecular near-infrared probe Cys(StBu)-Asp-Glu-Val-Asp-Lys(Cypate)-CBT (Cy-CBT) and prepared an intelligent nanoparticle Cy-CBT-NP, which is a fluorescence-quenched photothermal nanoparticle.

After tumor cells' uptake of Cy-CBT-NP, the tumor was treated with photothermal therapy under 808nm laser irradiation. During the PTT, the tumor cell eventually died and the Caspase 3 (Casp 3) was activated.

Casp 3 specifically recognized and cleaved DEVD substrates in the Cy-CBT-NP to yield Cy-CBT-NP-Cleaved which was accompanied by near-infrared fluorescence (NIF), turning the fluorescence "On".

Because the PTT efficiency, Casp3 activity, and the turned "On" NIR fluorescence intensity are positively correlated, this intelligent nanoparticle Cy-CBT-NP can be used to evaluate the tumor photothermal efficiency in real time.

Compared with the traditional tumor efficiency evaluation method, the strategy is real-time and can help doctors adjust the treatment plan in time.

Credit: 
University of Science and Technology of China

Spintronics: Researchers show how to make non-magnetic materials magnetic

A complex process can modify non-magnetic oxide materials in such a way to make them magnetic. The basis for this new phenomenon is controlled layer-by-layer growth of each material. An international research team with researchers from Martin Luther University Halle-Wittenberg (MLU) reported on their unexpected findings in the journal Nature Communications.

In solid-state physics, oxide layers only a few nanometres thick are known to form a so-called two-dimensional electron gas. These thin layers, separated from one another, are transparent and electrically insulating materials. However, when one thin layer grows on top of the other, a conductive area forms under certain conditions at the interface, which has a metallic shine. "Normally this system remains non-magnetic," says Professor Ingrid Mertig from the Institute of Physics at MLU. The research team has succeeded in controlling conditions during layer growth so that vacancies are created in the atomic layers near the interface. These are later filled in by other atoms from adjoining atomic layers.

The theoretical calculations and explanations for this newly discovered phenomenon were made by Ingrid Mertig's team of physicists. The method was then experimentally tested by several research groups throughout Europe - including a group led by Professor Kathrin Dörr from MLU. They were able to prove the magnetism in the materials. "This combination of computer simulations and experiments enabled us to decipher the complex mechanism responsible for the development of magnetism," explains Mertig.

Credit: 
Martin-Luther-Universität Halle-Wittenberg

Bone-anchored leg prostheses also prove to be a valuable procedure after 5-year follow-up

After above-knee amputation, there is the option of a prosthesis that is placed directly in the thigh bone (osseointegration). Despite the fact that bone-anchored prostheses have been used for thirty years, researchers at the Radboud University Medical Center have now published the first long-term evaluation of such a prosthesis. It turns out that the procedure is not without stoma problems, but that these can usually be treated with simple measures and that the osseointegration implant system leads to a permanent improvement in mobility and quality of life.

This study was published yesterday in the latest edition of Journal Of Bone And Joint Surgery.

Options for the attachment of the prosthetic leg after amputation

Bone-anchored prostheses offer a number of important advantages over traditional 'socket' prosthetics, which must fit snugly over the stump and be held in place by a suction or suspension system. To place a bone-anchored prosthesis, a 14 cm steel pin must first be inserted into the remaining portion of the femur bone. In a few weeks this coated pin grows into the bone, after which an adapter is attached that protrudes a few centimeters through the skin (via a stoma). The wearer can attach or detach the artificial leg to this part with a quick coupling connector.

Strong improvement in mobility and quality of life despite complications

In this study, clinical researcher David Reetz and surgeon Jan Paul Frölke, along with their colleagues from the rehabilitation and orthopedics department at Radboudumc, looked at 42 patients who had received such a prosthesis, and performed a follow-up study of the five years after surgery. A full follow-up was obtained in 39 of the 42 patients. The most common complication was infection, in 77% of patients - mostly superficial and in the first two years. The vast majority (95%) were mild to moderate infections that did not require surgical treatment. Fourteen patients experienced irritation around the stoma where the pin protrudes through the skin, and they underwent minor surgery to re-shape the soft tissue.

After receiving their implants, patients increased the number of hours per week they could use their prosthesis: from an average of 56 hours with their previous socket prosthesis to 101 hours with the bone-anchored prosthesis. The bone-anchored prostheses also improved health-related quality of life (HRQoL): on a 100-point scale, the average score increased from 33 to 75.

Frölke: "We received a lot of skeptical reactions from colleagues who didn't believe in it, even after we published excellent results after 2 years of follow-up. Thanks to the trust that patients placed in us, we have continued and we can now conclude that this is the new gold standard in people with sleeve-related problems including about half of all people with a leg amputation. "

Next steps

This study adds to existing evidence showing other benefits of bone anchored prostheses, including more natural and stable control of the prosthesis, improved walking and sitting conditions and avoidance of the many problems associated with the sleeve prosthesis, such as blisters.

Reetz notes, "Next steps in clinical research should include studies aimed at optimizing the stoma using a unified registry system, and further developing the implant design and safety of bone-anchored prostheses in patients with vascular disease. This is by far the largest group but has not been taken into account in this study. "

Credit: 
Radboud University Medical Center

Anode material for safe batteries with a long cycle life

image: Researchers hope that new materials help to build safe and durable high-performance cells.

Image: 
Julia Maibach, KIT

Researchers at Karlsruhe Institute of Technology (KIT) and Jilin University in Changchun/China investigated a highly promising anode material for future high-performance batteries - lithium lanthanum titanate with a perovskite crystal structure (LLTO). As the team reported in the Nature Communications journal, LLTO can improve the energy density, power density, charging rate, safety, and cycle life of batteries without requiring a decrease of the particle size from micro to nano scale. (DOI: 10.1038/s41467-020-17233-1)

The demand for electric vehicles is increasing, accompanied by a growing need for smart grids that ensure a sustainable energy supply. These and other mobile and stationary technologies require suitable batteries. Storing as much energy as possible in the smallest possible space with the lowest possible weight - lithium-ion batteries (LIB) still meet this requirement best. The research aims at improving the energy density, power density, safety, and cycle life of these batteries. The electrode material is of major importance here. Anodes of lithium-ion batteries consist of a current collector and an active material applied to it that stores energy in the form of chemical bonds. In most cases, graphite is used as the active material. However, negative electrodes made of graphite have a low charging rate. Moreover, they are associated with safety issues. Among the alternative active materials, lithium titanate oxide (LTO) has already been commercialized. Negative electrodes with LTO present a higher charging rate and are considered to be safer than those made of graphite. The drawback is that lithium-ion batteries with lithium titanate oxide tend to have a lower energy density.

The demand for electric vehicles is increasing, accompanied by a growing need for smart grids that ensure a sustainable energy supply. These and other mobile and stationary technologies require suitable batteries. Storing as much energy as possible in the smallest possible space with the lowest possible weight - lithium-ion batteries (LIB) still meet this requirement best. The research aims at improving the energy density, power density, safety, and cycle life of these batteries. The electrode material is of major importance here. Anodes of lithium-ion batteries consist of a current collector and an active material applied to it that stores energy in the form of chemical bonds. In most cases, graphite is used as the active material. However, negative electrodes made of graphite have a low charging rate. Moreover, they are associated with safety issues. Among the alternative active materials, lithium titanate oxide (LTO) has already been commercialized. Negative electrodes with LTO present a higher charging rate and are considered to be safer than those made of graphite. The drawback is that lithium-ion batteries with lithium titanate oxide tend to have a lower energy density.

The team around Professor Helmut Ehrenberg, head of the Institute for Applied Materials - Energy Storage Systems (IAM-ESS) of KIT, now investigated another highly promising anode material: lithium lanthanum titanate with a perovskite crystal structure (LLTO). According to the study, which was carried out in collaboration with scientists from Jilin University in Changchun (China) and other research institutes in China and Singapore, LLTO anodes have a lower electrode potential compared to commercialized LTO anodes, which allows for a higher cell voltage and a higher capacity. "Cell voltage and storage capacity ultimately determine the energy density of a battery," explains Ehrenberg. "In the future, LLTO anodes might be used to build particularly safe high-performance cells with a long cycle life." The study contributes to the work of the research platform for electrochemical storage, CELEST (Center for Electrochemical Energy Storage Ulm & Karlsruhe), one of the largest battery research platforms worldwide, which also includes the POLiS excellence cluster.

Besides energy density, power density, safety and cycle life, the charging rate is another determining factor for the suitability of a battery for demanding applications. In principle, the maximum discharge current and the minimum charging time depend on the ion and electron transport both within the solid body and at the interfaces between the electrode and electrolyte materials. To improve the charging rate, it is common practice to reduce the particle size of the electrode material from micro to nano scale. The study, which was published in the Nature Communications journal by KIT researchers and their cooperation partners, shows that even particles of a few micrometers in size in LLTOs with a perovskite structure feature a higher power density and a better charging rate than LTO nanoparticles. The research team attributes this to the so-called pseudocapacitance of LLTO: Not only are individual electrons attached to this anode material, but also charged ions, which are bound by weak forces and can reversibly transfer charges to the anode. "Thanks to the larger particles, LLTO basically enables simpler and more cost-effective electrode manufacturing processes," explains Ehrenberg.

Credit: 
Karlsruher Institut für Technologie (KIT)

New CT scanning method may improve heart massage

video: A look inside cardiopulmonary resuscitation: A 4D computed tomography model of simulated closed chest compression. A proof of concept

Image: 
Kasper Hansen/Jonathan Bjerg Moeller/Aarhus University

Rapid first aid during cardiac arrest makes the difference between life and death. But what happens to the heart and the internal organs when people come running and begin to give well-meaning but heavy-handed heart massage as they attempt to keep the person who has suffered a cardiac arrest alive?

A research collaboration between the Department of Forensic Medicine at Aarhus University, Denmark, and the East Midlands Forensic Pathology Unit at the University of Leicester in the UK now offers an answer to this question.

Using a new CT scanning method, the researchers show how the chest and abdominal region of a deceased person move during simulated heart massage.

"Specifically, we've simulated heart massage by compressing the chest of a deceased person in a controlled manner in precisely the same way as would happen with heart massage. Though with the difference that this was done gradually and in slow motion while the whole process was CT scanned at the same time," explains Kasper Hansen, assistant professor at the Department of Forensic Medicine at Aarhus University and the lead author of the study, which has been published in the scientific journal Resuscitation.

The method can be compared with a stop motion video production, but where each image in the video has been replaced by a complete 3D CT scan. The method reproduces the organs movements during heart massage in a very detailed way and makes it possible to perform advanced imaging analysis on the volumetric dynamic CT dataset.

According to the Danish Heart Foundation, in Denmark 5,400 people suffer cardiac arrest outside of the hospitals every year, with approx. 16 per cent of them surviving. Although more people than previously survive thanks to stronger efforts in general resuscitation training and improved rehabilitation, there is still room for improvement in resuscitation techniques and procedures. Kasper Hansen hopes that this is where the new CT scanning method will prove useful.

"The goal of heart massage is blood circulation, but we don't know enough about how the blood is pumped onwards, and why certain characteristic heart massage injuries such as lesions on the internal organs occur," he says.

"There are many unknowns in connection with resuscitation. The new technique makes it possible to examine different aspects of heart massage. Using the method allows us to directly study the organ movements, and may help to clarify the basis for important physiological mechanisms. Because the scans have been carried out on a deceased person, it hasn't been possible to measure the blood flow directly. However, the method clearly demonstrates how, for example, the heart is affected during heart massage, and we can therefore gain a better understanding of the critical mechanisms during heart massage," says Kasper Hansen.

In connection with the scientific publication, the study presents five videos that have been exported with so-called predefined display settings from the specialised imaging software.

"Specialised radiological software is needed to be able to utilise and show the full potential of the method and what it can deliver. In the article we therefore use the videos as a practical and known format to communicate how our new method is able to contribute to creating new insight into different elements of heart massage for experts within the field. Furthermore, we believe that anyone who has completed a first aid course will be able to relate to the videos. So we also hope that these videos will be fully utilised in the general first aid courses," says Kasper Hansen.

"Our results are a fine example of how research on the deceased can help the living, which is a mantra within forensic medicine research all over the world. The relatives of the deceased person used in this study have agreed to the experiment being carried out and to the publication of the results." This is of invaluable importance for this type of research, emphasises Kasper Hansen.

"It helps to bring us closer to our goal, which is for the method we present in the study to contribute to the development of better and more effective procedures for the treatment of cardiac arrest - and in this way to more people surviving a cardiac arrest," says Kasper Hansen.

About the study

The study is experimental novel method basic research.

The project was carried out in a collaboration between researchers from Aarhus University and the University of Leicester, UK.

The study was supported by a scholarship from the "Resuscitation Council (UK)".

Credit: 
Aarhus University

Fuel from disused tyres

Used tyres pose a serious environmental risk owing to the damage that may be caused when they are stored in the environment. They are emerging in ever greater numbers from one year to the next in developed countries so revalorizing them is a subject that is attracting great interest and is being spurred on by the increasingly stringent regulations in terms of their management.

"Pyrolysis is a hugely interesting alternative when it comes to revalorizing tyre materials in order to obtain alternative fuels and petrochemical products with high added value. In this context, pyrolysis involves degrading the rubber of the tyre by applying heat in the absence of oxygen. The products and their yield depend on the conditions in which the pyrolysis is carried out," said Miriam Arabiourrutia-Gallastegui, lecturer in the UPV/EHU's PROCAT-VARES (Catalytic Processes-Waste Valorization) group.

In a paper recently published in the journal Renewable and Sustainable Energy Reviews, the research group analysed the most important advantages in valorizing used tyres using catalytic pyrolysis. "The main interest in valorizing tyre waste by pyrolysis is based on the potential of the products obtained: gas, liquid and a solid known as char. The yield and composition of each of them depend on the pyrolysis conditions," said Arabiourrutia.

"Liquid is the main product obtained in catalytic pyrolysis. This liquid is basically what is of the greatest interest because it could be used as fuel if it were to be incorporated, for example, into a refinery. Its composition is complex and includes compounds of different types (aromatics, paraffins, olefins and naphthenes), plus sulphur compounds that limit its direct use as a fuel. So the interest in catalytic pyrolysis tends to be linked to the improvement in the properties or yield of this part. So with respect to catalytic pyrolysis great interest has been placed in the production of chemical products, such as aromatic compounds (benzene, toluene, etc.), because they have commercial applications," explained the UPV/EHU researcher.

"Pyrolysis gases can also be used as fuel to produce energy. Finally, char is the solid left behind that is not degraded and mainly comprises the carbon black present in the tyre; carbon black is the compound that provides the tyre with its anti-abrasive properties. The possible activation of char for use as activated carbon is being explored; it could be reused as carbon black in the manufacture of tyres," Arabiourrutia added.

"In the process we used and based on the use of the conical spouted bed reactor, catalytic pyrolysis has certain, very specific conditions: the time the gases generated remain in the reactor is short and that promotes a series of reactions which, for example, lead to the production of a high yield of the liquid part. We have also seen that, more than anything, this process enables the liquid product obtained to be used in refineries to obtain fuel," stressed Miriam Arabiourrutia-Gallastegui.

As the researcher pointed out, "thanks to all these pieces of work we are gradually adjusting and improving the pyrolysis process to try and bring about a distribution of products with a more suitable composition with a view to their potential application as fuel or raw material to obtain compounds of interest".

Credit: 
University of the Basque Country