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University of Delaware molecular biologist Mona Batish and collaborators at Harvard Medical School and University of California, Los Angeles, have identified a new circular ribonucleic acid (RNA) that increases tumor activity in soft tissue and connective tissue tumors.

Finding this new genetic unit has the potential to advance understanding of the genetics of cancer and how cancer is identified and treated.

The researchers recently reported their findings in a new paper in Cell Research, a Nature journal. Batish was a co-author on the team that included Jlenia Guarnerio, the paper's lead author and assistant professor of biomedical sciences at UCLA and at Cedars-Sinai Medical Center; Pier Paolo Pandolfi, the Aresty Endowed Chair of Medicine and professor of medicine and pathology at Harvard Medical School; and colleagues from Harvard Medical School's Beth Israel Deaconess Medical Center, Rutgers University and Aalborg University Hospital in Denmark.

A word about circular RNA

RNA is a single-stranded molecule that is made by the DNA -- the code of life -- in our bodies. Messenger RNA (mRNA) acts as a courier, transporting instructions from the DNA code to protein-making machines and thus dictating the composition of proteins in a cell. Apart from mRNA, there are many other types of RNA, which do not carry code for proteins but perform other important functions in cells. Collectively, these are known as non-coding RNAs.

A new class of non-coding RNA, called circular RNA, was discovered in the 1970s. Circular RNA (circRNA) was initially thought to be a virus because most RNA molecules are linear, meaning that their genetic sequence always moves in a forward direction. By contrast, circRNA is circular, even though it shares the same genetic sequence as linear RNA.

"Under certain conditions, RNA processing systems can get tricked into thinking they are supposed to join the ends," said Batish, an assistant professor of medical and molecular sciences in UD's College of Health Sciences. "When this error occurs, it creates a backwards loop in the RNA's genetic sequence and then keeps on going-- kind of like when you get a kink in the middle of a necklace." This loop separates off and persists as a circular RNA inside the cell.

For a long time, researchers thought this error, a process known as back splicing, didn't mean anything. But when genome sequencing came about in the 1990s, scientists started finding circular RNA in brain tissue and other tissues. By 2014, they realized that circular RNA was important and, today, there is a whole field looking at circular RNA as a biomarker for disease, particularly cancers.

According to Batish, the role of circRNA in tumor progression has been understudied.

In the paper, the researchers describe a new circRNA generated by a gene called Zbtb7a found in soft tissue tumors, such as mesenchymal tumors. In its linear form, this RNA makes a tumor-suppressing protein that stops the growth of cancer, according to previous research out of Pandolfi's Harvard research lab. However, once the same RNA makes a circRNA (that is, gets a "kink"), the circular RNA works independently to make the tumor more active, effectively silencing the tumor-suppressing protein.

According to Batish, this is the first time that this type of antagonistic, tumor-promoting role of circRNA has been shown in connection with linear RNA with the same genetic sequence.

Theoretically, both RNA strands should perform the same function because they originate from the same genetic material, but they don't.

Method helps validate findings

In order to validate their findings, the researchers needed a way to tell whether an RNA was linear or circular since they share the same genetic code. This is where Batish's expertise came in.

"You don't 'see' RNA, per se, so you have to label it," Batish said. "But, if you label it with something that is sequence-specific, it's hard to tell if it's linear or circular because the genetic code looks the same."

Batish had previously worked on probes that "light up" each RNA in an individual cell as a single bright spot under the fluorescence microscope to understand how biological systems operate on a cellular level. She adapted this method for distinguishing circular RNA from its linear RNA counterpart from the same gene by using a color combination method.

"Essentially, it's like creating a pattern of beads on a necklace. Say the RNA we are working with contains red and green beads. We know that circular RNA is a closed circle of green beads only, so we add probes for both red and green beads and then image them under a fluorescence microscope," said Batish. "If we see a signal for both red and green at the same spot, which appear as yellow (combination of green and red) in the sample, we know it is linear RNA. If it doesn't have red, it must be circular RNA."

This method allowed them to simultaneously visualize linear and circular RNA within a single cell.

"This is the first time that we have realized that RNA with the same genetic sequence can sometimes perform two roles, in this case both as a cancer suppressor and a cancer promoter, and that this change in role occurs at the RNA-level," said Batish. "The identification of this new genetic unit opens up new opportunities to understand the genetics of cancer and the role of circRNA in cancer biology."

And because a unique junction is created where the ends of circRNA come together, Batish said they may be able to develop treatment protocols to uniquely target the circular RNA, but leave the linear RNA alone. This could provide a way to target treatment to stop the circular RNA from turning off the cancer-suppressing effect in the body.

So, what's next for Batish?

While this research study focused on connective and soft tissue tumors or diseases like mesenchymal tumors, Batish said the technique developed in her lab could be used on any cancer, because every cancer has circular RNA.

Batish plans to conduct experiments to see if what they have observed at the cellular level also occurs in tissue samples. Studying this expression in both healthy and diseased tissue, she said, would help her better understand the biosignature of circular RNA.

"If we can show that it persists in samples that are left out and not treated properly, that has real value. This is because circular RNA is differentially expressed, meaning my lungs will express different circular RNA than my brain and other tissues or organs," said Batish.

"So imagine if you have that biosignature, and you can draw blood from a patient and look at what circular RNAs they have, you might be able to identify what kind of cancer a person has by these cancer markers instead of sending the patient for imaging or other testing. People are working on this research, so we'll see."

Batish also wants to study whether circular RNA found in tumors is present in cell signaling molecules known as extracellular vesicles. She describes these vesicles as letters, FedEx packages that cells put together and deliver to neighboring cells to tell them what's going on nearby.

"One thought is that cancer may actually be hijacking this delivery system, adding 'fake news' into the packages that tell the neighboring cells that all is okay in their cell, while creating a microenvironment in which the cancer can grow," she said.

Since every cancer starts with one single cell, Batish wants to explore the role circular RNA may play in this messaging. It might provide a pathway to understand how cell-to-cell communication is used by tumor cells.

She also wants to develop tools to enable live imaging of circular RNA in cells. Working in collaboration with Jeff Caplan, director of the Bio-Imaging Center at the Delaware Biotechnology Institute, Batish is exploring ways to add a "tracking device" of sorts into the cell that would allow them to follow the signal in real-time as circular RNA is formed.

"That would be really groundbreaking if we can do it," said Batish.

High levels of pollutants, such as industrial fluids and mercury, may have accumulated in the blubber and skin of one of the largest coastal populations of dolphins in Europe, a study in Scientific Reports indicates. Mercury concentrations found in 82 dolphins living in the English Channel are among the highest concentrations observed in the species, the work suggests.

Toxic organic pollutants, particularly those containing chlorine, were banned from most developed countries in the 1970s and 1980s; however, they can still be detected even in the deepest ocean marine life. These organic compounds are able to dissolve in fats and oils, and consist of the by-products of various industrial processes and pesticides, among others. Bottlenose dolphins are often used to study levels of environmental pollutants, as the organic compounds accumulate within their thick layer of fatty tissue.

Krishna Das and colleagues assessed levels of organic pollutants in the blubber and levels of mercury in the skin of 82 free-ranging bottlenose dolphins inhabiting the Normanno-Breton Gulf in the English Channel. They found high concentrations of pollutants in the blubber, predominantly made up of chlorine-containing compounds from industrial fluids (91% in males and 92% in females). Moreover, the levels of mercury in the skin samples were similar to concentrations previously described for bottlenose dolphins in the Mediterranean Sea and Florida Everglades, two sites already known for their high mercury contamination levels.

The authors suggest that the Normanno-Breton Gulf should become a special area of conservation to protect one of the largest costal populations of bottlenose dolphins in Europe.

USC scientists have surmounted a big roadblock in regenerative medicine that has so far constrained the ability to use repurposed cells to treat diseases.

The researchers figured out how to reprogram cells to switch their identity much more reliably than present capabilities allow. The technique uses enzymes to untangle reprogramming DNA, somewhat similar to how a coiffeur conditions tangled hair. The technique works with near-perfect efficiency -- in mice and humans -- for all types of cells tested in the laboratories of USC's stem cell center.

The findings are significant because they clear an obstacle to help scientists find treatments for a wide range of diseases, especially neurologic impairments and conditions such as hearing loss.

"This is a strategy for greatly improving our ability to perform cellular reprogramming, which could enable the regeneration of lost tissues and the study of diseases that cannot be biopsied from living patients today," said Justin Ichida, assistant professor in the department of stem cell biology and regenerative medicine at the Keck School of Medicine of USC.

The findings appear today in Cell Stem Cell in a research paper entitled, "Mitigating antagonism between transcription and proliferation allows near-deterministic cellular reprogramming." Ichida is the lead author, joined by a team of researchers at the Keck School of Medicine.

How USC researchers untangled cellular reprogramming

Cellular reprogramming has enormous potential as a disease cure because it enables scientists to study cells and molecular processes at each step of disease progression in controlled conditions that have, until now, been impossible.

Reprogramming involves changing one cell into another type of cell, such as a blood cell into a muscle or nerve cell. That's important for medical research because the technique can be used to recreate tissues lost to disease and to study diseases in tissues that cannot be biopsied from living patients.

The technique has been known for decades but hasn't met its potential. According to the USC team, that's because DNA does not respond well when manipulated to change itself. DNA molecules are twisty by nature, due to the double helix configuration. Reprogramming DNA requires uncoiling, yet when scientists begin to unravel the molecules, they knot up tighter. As a result, nucleotides become much more difficult to work with and cells won't replicate properly, Ichida explained. Current untangling techniques only work 1% of the time.

"Think of it as a phone cord, which is coiled to begin with, then gets more coils and knots when something is trying to harm it," Ichida said.

To smooth the kinks, the researchers treated cells with a chemical and genetic cocktail that activated enzymes called topoisomerases. The process works by using the enzymes to open the DNA molecules, release the coiled tension and lay it smoothly. In turn, that leads to more efficient cellular reprogramming, which increases the number of cells capable of simultaneous transcription and proliferation, which is needed to promote tissue growth. It's the equivalent of a DNA detangler that relaxes the tension of reprogramming transcription and makes it easier to replicate new cell colonies or tissues in a lab.

The technique has multiple advantages over existing current practice. For example, it worked nearly 100% of the time. It was proven in human and animal cells. It can be employed today in laboratories to study disease development and drug treatments. It has immediate utility for studying schizophrenia, Parkinson's, ALS and other neurological diseases; in those instances, new cells can be created to replace lost cells or acquire cells that can't be extracted from people.

Moreover, the technique does not involve stem cells; the reprogrammed cells are not brand new but the same age as the parent cell, which is advantageous for studying age-related disease. The reprogrammed cells may be better at creating age-accurate in vitro models of human disease, which are useful to study diverse degenerative diseases and accelerated aging syndromes.

"The key is to understand development of disease at a cellular level and how disease affects organs," Ichida said. "This is something you can do with stem cells, but in this case, it skips a stem cell state. That's important because stem cells reset epigenetics and make new, young cells, but this method allows you to get adult cells of same age to better study diseases in aged individuals, which is important as the elderly suffer more diseases."

This latest advance in regenerative medicine complements other recent technological gains, including gene editing, tissue engineering and stem cell development. It represents a convergence in regenerative medicine moving scientists closer to treating many diseases. It has practical utility to accelerate targeted medical treatments and precision medicine.

"A modern approach for disease studies and regenerative medicine is to induce cells to switch their identity," Ichida said. "This is called reprogramming, and it enables the attainment of inaccessible tissue types from diseased patients for examination, as well as the potential restoration of lost tissue. However, reprogramming is extremely inefficient, limiting its utility. In this study, we've identified the roadblock that prevents cells from switching their identity. It turns out to be tangles on the DNA within cells that form during the reprogramming process. By activating enzymes that untangle the DNA, we enable near 100% reprogramming efficiency."

ST. PETERSBURG, Fla. (September 12, 2019)- A new study from the University of South Florida St. Petersburg and Eckerd College estimates the waters of Tampa Bay contain four billion particles of microplastics, raising new questions about the impact of pollution on marine life in this vital ecosystem.

This is the first measurement of microplastic abundance and distribution in the region. Researchers hope the findings will provide necessary data to inform the debate around policies to reduce plastic in the marine environment.

Microplastics are tiny plastic particles less than 1/8 of an inch, barely or not at all visible to the eye. They come from the breakdown of larger plastics, such as water bottles, fishing gear and plastic bags, or from synthetic clothing and other items that contain elements of plastic. Previous studies have found these particles in every ocean on the planet and even in the Arctic.

"Very little is known about how much microplastics are out there and the full consequences of these particles on marine life," said Kinsley McEachern, the first author of the study and a recent Environmental Science and Policy graduate student at USF St. Petersburg. "But emerging research indicates a wide range of impacts on marine ecosystems from the large accumulation of microplastics."

Since particles are similar size as plankton, filter feeders such as oysters, clams, many fish and some birds ingest microplastics, allowing them to enter the food chain. Persistent organic pollutants, including toxic pesticides, and metals can stick to their surfaces, making ingestion potentially that much more damaging. Effects include cellular damage, reproductive disruption and even death.

The study revealed that the predominant type of these tiny particles in Tampa Bay - in both water and sediment - are thread-like fibers that are generated by fishing lines, nets and washing clothes. Synthetic fibers are released from clothes while they are being laundered, discharged to wastewater treatment plants and eventually released into the bay.

The next largest source are fragments that come from the breakdown of larger plastics.

"These plastics will remain in the bay, the gulf and ocean for more than a lifetime, while we use most plastic bags and bottles for less than an hour," said David Hastings, Principal Investigator of the study, Courtesy Professor at USF College of Marine Science and a recently retired Professor of Marine Science and Chemistry at Eckerd College. "Although it is tempting to clean up the mess, it is not feasible to remove these particles from the water column or separate them out from sediments."

"Only by removing the sources of plastics and microplastic particles can we successfully decrease the potential risks of plastics in the marine environment," added McEachern.

Researchers found the largest concentrations of microplastics in water occurred after intense and long rainfall events, while in sediments the greatest amount of microplastics were located close to industrial sources.

For more than a decade, Hastings led annual research cruises in Tampa Bay with Eckerd College students to collect water samples and plankton. During these trips, he and his students were also seeing small pieces of plastic.

"We were looking at plankton, which form the base of the marine food web. But when we put the samples underneath the microscope, we were astonished to find many brightly colored pieces of microplastic. We wanted to learn more," said Hastings.

Teaming up with McEachern, who was interested in focusing her graduate research on this issue, USFSP Associate Professor of Chemistry Henry Alegria and the Environmental Protection Commission of Hillsborough County, they set about counting microplastics in the region at 24 stations over a 14-month period. Collecting stations were located at the mouths of major rivers, near industrial facilities and in relatively pristine coastal mangroves. Particles believed to be plastic were probed with a hot dissecting needle. If the material quickly melted or disfigured, the sample was classified as a microplastic.

On average, the study found four pieces of microplastic per gallon of water at all sites, and more than 600 pieces of microplastic per pound of dry sediment. Extrapolating those findings to the entire Tampa Bay estuary, the researchers estimated there are approximately four billion particles in the water and more than 3 trillion pieces in surface sediments.

"This is a very important study in that it is the first for our region and shows the extent of the problem," said Alegria. "It also provides a vital baseline on total numbers and distribution. This is important for management plans moving forward to show whether future actions and policies are effective at reducing these particles in our environment."

Researchers say the findings, though substantial, might also be conservative, since collection in the bay occurred several feet below the water surface, likely missing any buoyant microplastics at the surface.

"We collected only a few pieces of Styrofoam, most likely because we sampled below the surface and foam floats at the surface," explained Hastings.

Plastic pollution in the marine environment has been a concern for decades. However, only recently have scientists started to uncover the widespread abundance of microplastics in the environment. With mounting physical evidence of plastic pollution, there have been greater calls for action in coastal communities around the world. Recently bans on plastic bags and single-use plastics have been enacted by some local governments in Tampa Bay to reduce marine pollution and protect Florida's largest open-water estuary.

The findings of billions of particles of microplastics in Tampa Bay waters could bring even greater calls for action and influence future decisions in the region and beyond. Researchers at USF St. Petersburg and Eckerd College are conducting further research to more fully understand microplastic pollution in the marine environment.

A strong ability in languages may help reduce the risk of developing dementia, says a new University of Waterloo study.

The research, led by Suzanne Tyas, a public health professor at Waterloo, examined the health outcomes of 325 Roman Catholic nuns who were members of the Sisters of Notre Dame in the United States. The data was drawn from a larger, internationally recognized study examining the Sisters, known as the Nun Study.

The researchers found that six per cent of the nuns who spoke four or more languages developed dementia, compared to 31 per cent of those who only spoke one. However, knowing two or three languages did not significantly reduce the risk in this study, which differs from some previous research.

"The Nun Study is unique: It is a natural experiment, with very different lives in childhood and adolescence before entering the convent, contrasted with very similar adult lives in the convent," said Tyas. "This gives us the ability to look at early-life factors on health later in life without worrying about all the other factors, such as socioeconomic status and genetics, which usually vary from person to person during adulthood and can weaken other studies."

Tyas added, "Language is a complex ability of the human brain, and switching between different languages takes cognitive flexibility. So it makes sense that the extra mental exercise multilinguals would get from speaking four or more languages might help their brains be in better shape than monolinguals."

The researchers also examined 106 samples of the nuns' written work and compared it to the broader findings. They found that written linguistic ability affected whether the individuals were at greater risk of developing dementia. For example, idea density - the number of ideas expressed succinctly in written work - helped reduce the risk even more than multilingualism.

"This study shows that while multilingualism may be important, we should also be looking further into other examples of linguistic ability," said Tyas. "In addition, we need to know more about multilingualism and what aspects are important -- such as the age when a language is first learned, how often each language is spoken, and how similar or different these languages are. This knowledge can guide strategies to promote multilingualism and other linguistic training to reduce the risk of developing dementia."

EAST LANSING, Mich. -- Stems, leaves, flowers and fruits make up the biggest chunk of potential living space for microbes in the environment, but ecologists still don't know a lot about how the microorganisms that reside there establish and maintain themselves over the course of a growing season.

In a new study in Nature Communications, Great Lakes Bioenergy Research Center scientists at Michigan State University have focused on understanding more about the plant regions above the soil where these microbes can live, called the "phyllosphere." Ashley Shade, MSU assistant professor of microbiology and molecular genetics, and her lab classified core members of this community in two bioenergy cropping systems: switchgrass and miscanthus. In so doing, the group made important distinctions about how these communities assemble - and how they're connected to microbes in the soil.

Microorganisms that dwell in the phyllosphere are thought to play a role in their host's growth and health. And, like their subterranean kin, the topside microbiome affects how much phosphorus, nitrogen and other nutrients bioenergy crops can keep out of our waterways and atmosphere.

Shade says the first step in determining how to maximize production of these bioenergy crops is figuring out which taxa, or kinds of organisms, are long-term residents and which might just be passing through.

Pillars of the community

Shade and her colleagues wanted to ask two questions: does the phyllosphere microbiome change across seasons; and, if so, what role does the soil play in the yearly dance between plants and microbes? To find out, they tapped miscanthus and switchgrass fields at MSU's Kellogg Biological Station in Hickory Corners, established in 2008 as part of a GLBRC biofuel cropping system experiment.

Shade's lab members sampled microbial communities from bioenergy crop leaves every three weeks for one full growing season for miscanthus and two for switchgrass. They defined core microbes as those that consistently could be detected on leaves at the same time points across their fields, and that persistently appeared over sampling periods.

"If we found a microbe in one field, but not another, it couldn't be called a core member at that specific interval," she said. "We also expect these communities to change with the seasons, so we want to make sure we capture as many of those important taxa as possible."

It turns out that many core microbes on bioenergy plant leaves originate in the soil and are fairly consistent across seasons. This means the phyllosphere microbiome can be targeted for cultivation, just like the crops on which they grow.

The team identified hundreds of leaf microbiome members and compared them to thousands that live in the soil with a deep sequencing technique provided by the Joint Genome Institute, a Department of Energy Office of Science user facility.

"Because of our relationship to JGI, we were able to get some really good coverage of the diversity in our soil communities, something we couldn't have done on our own," Shade said.

Some microbes found at consistent but low levels in the soil turned out to be core members of leaf communities.

"This suggests that the leaf environment is a specific habitat where certain organisms fit," Shade said. "The fact that we find them in the soil means the ground is a possible reservoir for these taxa."

To evaluate the idea further, Shade and her team set up a statistical model to mimic results as if microbes were randomly distributed between a plant's leaves and the nearby soil, then compared the output to their real-life observations.

The models showed that, indeed, the microbial community on miscanthus and switchgrass leaves aren't distributed by chance.

"They're not just randomly blowing onto leaves and sticking, so something in the environment is selecting for these taxa above the soil," Shade said. "Because the patterns on the ground are different than the ones we see on the leaves, there's reason to believe many of these core leaf members are there on purpose."

Whittling down the taxa

The next step will be to home in on which of the core microbiome members have important functions for the plant.

"Now that we have a whole bunch of community data from the microbiome that includes thousands of taxa," Shade said, "we can understand which of these core members are just hanging out on the plant, and which ones have an impact on growth and health."

"If we can understand how that microbial community is changing its interactions with its host over a season, we might be able to leverage that to benefit the plant," she added.

Scientists have identified a molecular pathway that contributes to the development of pulmonary arterial hypertension (PAH), a severe, often fatal condition that has no cure.

The discovery, published Sept. 12, 2019, in Nature Communications, suggests a new target for developing new drug therapies for PAH, according to researchers at Cincinnati Children's Hospital Medical Center.

What is PAH?

This progressive disease is characterized by high blood pressure in the lungs, and affects adults and children. When left untreated, PAH can lead to fatal heart damage.

Scientists have long known that a process called vascular remodeling drives the thickening of lung arteries that contributes to the increased pressure. Reversing vascular remodeling could be curative.

PAH is a life-threatening disease in adults and can also complicate the repair of congenital heart disease in children,” says lead study investigator Rashmi Hegde, PhD, Division of Developmental Biology. “While progress is being made to develop treatments, there currently is no effective cure available. The new molecular pathway described by our study could be targeted to develop effective therapeutics for the disease."

Targeting the EYA3 protein may someday improve treatment

The current study describes a molecular pathway involving the protein Eyes Absent 3 (EYA3). This protein promotes vascular remodeling and could be targeted in the development of PAH therapeutics, Hegde says. EYA proteins have a mechanistically unique enzyme activity first identified by Hedge and her colleagues in 2003.

In this study, the research team manipulated transgenic mice with CRISPR gene editing technology to inactivate EYA3, which significantly protected the lung arteries from vascular remodeling. When researchers tested pharmacological inhibition with previously identified drugs that target the EYA3 pathway, significant reversal of vascular remodeling was seen in laboratory rat models.

What's next in PAH research?

Additional research is needed before a treatment strategy could be available for human testing. Beyond existing medications that target EYA3, the researchers want to design a treatment that even more precisely targets remodeling in PAH.

WASHINGTON -- For the first time, researchers have used ultra-thin layers of 2D structures known as metasurfaces to create holograms that can measure the polarization of light. The new metasurface holograms could be used to create very fast and compact devices for polarization measurements, which are used in spectroscopy, sensing and communications applications.

Metasurfaces are optical elements with nanoscale features and an overall thickness that is less than 1/50th that of a human hair. They can be made with standard microelectronics fabrication techniques, enabling mass production, and can be easily integrated into wafer-scale optical systems. Despite these promising features, they are not yet used in many practical applications.

In Optica, The Optical Society's journal for high impact research, a multi-institutional group of researchers report using metasurface holograms to effectively and quickly determine polarization at near-infrared to visible wavelengths. The new work represents a step toward functional metasurface-based devices to support a range of applications from telecommunications to chemical analysis.

"Holograms made from metasurfaces are an efficient and effective way to generate high-quality images with subwavelength resolution," said research team leader Xueqian Zhang from Tianjin University, China. "Our work uniquely applies metasurface holograms to polarization measurements, which could enable camera-size devices that measure polarization in one step without moving parts."

Measuring polarization directly

Although sunlight and most household light sources emit unpolarized light that oscillates in all directions, optical components such as filters can be used to produce polarized light that propagates in just a single plane -- typically vertical or horizontal. Analytical instruments such as spectrometers can measure how light polarization changes after interacting with a material to determine its physical properties. Different light polarizations can also be used to send multiple signals through optical fibers for telecommunications applications.

Conventional methods for determining polarization often require multiple measurements, bulky optical setups or precise adjustment of high-quality optical components to indirectly determine the polarization state. In the new work, the researchers instead used a metasurface to determine polarization directly by comparing the amplitude and phase of light waves that are polarized at right angles to themselves.

The metasurface generates two overlapping holographic images, one that is left-handed circularly polarized (LCP) and another that is right-handed circularly polarized (RCP). Circularly polarized light features an electric field oscillation plane that rotates to the left or right in a plane perpendicular to the direction of the wave.

"The overlapping images can be simply and quickly captured using a CCD camera," said Zhang.

"By analyzing the interference of the two holographic images, we can obtain the amplitude contrast and phase difference between the LCP and RCP components of the incident beam, thus identifying the polarization state."

Key to the new technique was an algorithm called Gerchberg-Saxton, which is widely used in holographic research. The researchers figured out how to modify this algorithm so that it could be used to identify the phase difference between the LCP and RCP components of the incident light in the overlapping holographic images.

Effective polarization measurements

The researchers demonstrated their new metasurface holographic approach by using it to measure the polarization states of illuminating light beams with known polarizations. The measured polarization states matched well with the known ones, confirming the effectiveness of the approach. In the future, the metasurface could be incorporated into a camera's photosensitive area to make a compact device for measuring polarization.

The metasurface the researchers used is based on the Pancharatnam-Berry phase (also known as geometric phase) method, which features relative phase responses that do not exhibit any dispersion. This allows the metasurface holograms to work over a broad range of wavelengths.

"Our method can be extended to many potential applications requiring polarization measurement, such as polarization spectroscopy, sensing and communications," said Zhang. "Polarization-encoded holography could also be used for security information transmission because only a receiver who knows the desired polarization states could decode information from the final holographic images."

Now that they have proved the concept, the researchers plan to improve the efficiency of the method and will compare its performance with conventional commercial instruments used to measure polarization.

Professor Sue Jordan from the University's College of Human and Health Sciences led the research which is newly published in the PLOS ONE journal. The study showed how care home residents' adverse side effects were picked up more effectively by their nurses and carers when a structured monitoring system was used alongside administration of mental health medicines.

The over-use of mental health medicines in care homes has long been a cause for concern, and insufficient patient monitoring has been seen as an important cause of medicines-related harms.

The new study examined the nurse-led medicines' monitoring system known as the Adverse Drug Reaction (ADRe) Profile which identifies and addresses the adverse effects that mental health medicines can have on patients.

This study worked with ten care homes caring for people prescribed mental health medicines to investigate:

The clinical impact of ADRe.

How to ensure the routine and continued use of ADRe in care homes.

How ADRe might enhance pharmacists' medication reviews.

The study found that nurses using ADRe picked up issues which resulted in nursing care being changed for 27 of 30 residents and medication for 17 patients being reviewed.

Other key findings were that nurses using ADRe found:

Antipsychotic medicines were reduced.

Eight of 30 residents were identified as being in pain, and ADRe helped to resolve this e.g. by recommending review of painkillers.

Six of 30 residents were short of breath and were referred for medication review.

Care plans were changed for five of nine residents that had suffered falls.

Residents were 'brighter' or less agitated or less aggressive when care changed to reduce antipsychotic medicines.

The research team also interviewed key people such as prescribers, pharmacists, nurses and care staff in the homes, residents, service users and relatives as well as policy makers and a care homes inspector. The responses were mainly favourable, because without ADRe treatable problems might be left unattended, but healthcare professionals said that time, understaffing and work demands were potential barriers to regularly using ADRe.

However patients and service users said continued monitoring was needed to avoid people becoming ill, their conditions deteriorating, mistakes being made or valuable information about a patient's condition not being picked up.

The study concluded that when ADRe is used routinely, it improves the lives of patients, helps to identify problems quickly, and results in better care and medication reviews. It also shows that as ADRe fully records a list signs and symptoms, it makes reviews by pharmacists easier and helps them make better decisions when changing, reducing or stopping medicines.

Professor Sue Jordan said: "Our study shows how simply checking patients for the signs and symptoms of possible adverse drug reactions improves the lives of the most vulnerable in society. It also shows that bringing patients' perspectives into medicines optimisation is complex, and the very complexity means that professionals may shy away from this potentially difficult task. The positive impact on patients' lives should persuade managers, service leaders and guideline developers to adopt ADRe - after all who wouldn't want to be checked for pain, breathlessness, sedation and tremor?"

Timothy Banner, study pharmacist, said: "ADRe is needed to meet the recommendations of Welsh Government for medicines optimisation Use of Antipsychotic medication in care homes, and these findings need to be implemented by healthcare professionals, policy makers and sector regulators to ensure patient safety and minimise any harm caused by adverse side effects."

Dr. Jeff Round, health economist, said: "This study shows how a simple and inexpensive tool in routine care can minimise preventable adverse side effects. There are significant resource and cost implications in failing to tackle the problem."

SINGAPORE, 12 September 2019 - Using cutting-edge technologies, researchers at Duke-NUS Medical School, Singapore, have developed the first genome-wide dataset on protein translation during fibroblast activation, revealing a network of RNA-binding proteins (RBPs) that play a key role in the formation of disease-causing fibrous tissue in the heart. Their findings, published in the journal Circulation, could help in the search for treatments for this condition.

Cardiac fibrosis, a condition characterised by scarring in the heart, is caused by the activation of fibre-producing cells called fibroblasts - which form one of the largest groups of cells in the heart - and underlies many heart diseases, including atrial fibrillation, dilated cardiomyopathy, and heart failure. This involves the transformation of fibroblasts into myofibroblasts, which leads to thickening and stiffening of the heart wall, making it less contractile and thus less able to pump blood around the body.

"Heart disease is a prominent cause of mortality, accounting for one in three deaths in Singapore. In most cases, they are preceded by the transition of resident fibroblasts to myofibroblasts," explained computational geneticist Dr Owen Rackham, corresponding author of the study and Assistant Professor in the Cardiovascular and Metabolic Disorders (CVMD) Programme at Duke-NUS. "Despite the serious risk and high prevalence of cardiac fibrosis, existing therapies are ineffective and there is an unmet need for new therapeutic approaches to prevent, limit, or reverse the condition."

Being able to disentangle the processes underlying the transformation of fibroblasts into myofibroblasts could help unveil novel molecular pathways underpinning disease onset and pathophysiology, and aid in the search for novel therapeutic targets. The team of researchers from Duke-NUS and colleagues in Germany and the UK investigated the processes that regulate the transcription of DNA code into RNA, and the translation of that code from RNA for protein synthesis during the transformation of fibroblasts into myofibroblasts.

"We found a staggering one-third of all genes undergo translational regulation during this pathogenic transition," highlighted Ms Sonia Chothani, first author of the study and a PhD student at Duke-NUS. "All these gene expression changes are missed or misinterpreted in traditional RNA-based studies."

The team first analysed the gene changes that occurred during DNA transcription and RNA translation at different time points in the fibroblast-to-myofibroblast transition. A computational analysis of this data identified specific regulatory processes affecting RNA translation. They then analysed RNA found in fibroblasts from tissue samples taken from patients with dilated cardiomyopathy. Many of the regulatory processes identified in the computational analysis were active in the diseased tissue samples.

Specifically, the researchers found RBPs play critical roles in the fibroblast-to-myofibroblast transformation. RBPs target RNA, affecting the translation of its code during protein synthesis. Inhibiting two of these RBPs, called PUM2 and QKI, limited the transformation of fibroblasts into myofibroblasts.

"There are more than 1,500 RBPs encoded in the human genome, but their role in the regulation of translation of target messenger RNAs remains largely unexplored. Our findings show the central importance of translational control in fibrosis, and highlight novel pathogenic mechanisms in heart failure," said Dr Rackham. "Just as transcription factors are emerging targets in pharmacology owing to their centrality in the dysregulation of transcription, we show that RBPs may play a similar role in the dysregulation of translation."

"Our study combines the use of primary cardiac fibroblasts and heart tissue samples with cutting-edge technologies, leading to the first genome-wide dataset on protein translation during fibroblast activation, which we were also able to follow-up in the diseased human heart," said Dr Stuart Cook, a senior co-author of the study, the Tanoto Foundation Professor of Cardiovascular Medicine and Director of Duke-NUS' CVMD Programme, and a Senior Consultant at the National Heart Centre Singapore. "The combination of in-house experiments and large public data repositories, together with the novel functional genomics approach we used to integrate various data types, provide a powerful tool to explore gene regulation."

Professor Patrick Casey, Senior Vice Dean for Research at Duke-NUS, commented, "Our ability to understand disease is being revolutionised by the availability of new technologies, whose power can best be realised by interdisciplinary teams combined with the development of methods that can address previously intractable questions. As exemplified in this study, the best way to do this is by bringing together scientific and clinical expertise with cutting-edge technology."

The researchers recommend future research to carefully reveal the interdependencies and cross-talks in the various stages of gene expression in order to be able to develop a holistic view of the regulatory process contributing to the manifestation of disease.

A team of researchers from Osaka University, in cooperation with Tokyo Institute of Technology, directly observed charge transfer and intermolecular interactions in artificial photosynthesis that occurs on a picosecond (ps) scale (10-12). With time-resolved attenuated total reflection (TR-ATR) spectroscopy in the terahertz (THz) region, they revealed the process of artificial photosynthesis material [Re(CO)2(bpy) {P(OEt)3}2](PF6) in Triethanolamine (TEOA) solvent as a reductant. Their research results were published in Scientific Reports.

Artificial photosynthesis, or a photocatalytic reaction to produce chemical energy from carbon oxide (CO2) and light, is, as with a solar battery, a promising next-generation clean energy. In particular, the photocatalytic reaction using rhenium (Re) complexes is highly efficient. In order to create efficient photocatalytic molecules, it is necessary to examine how the photocatalytic reaction occurs on a picosecond timescale. However, it was impossible to directly observe various phenomena in the photocatalytic reaction.

The researchers tried to obtain information about changes in relative positions of molecules and charge transfer by using time-resolved attenuated total reflection (TR-ATR) spectroscopy. Photocatalytic molecules which absorb light facilitate CO2 reduction to CO, bringing it to a higher energy level. They examined how charge transfer from the reductant TEOA to Re occurred in a photocatalytic reaction.

Because the use of THz waves, whose frequency is lower than those of visible light and infrared light, reveals changes in intermolecular vibrations (that is, binding energies between two neighboring molecules) in the THz (low-frequency) region, this allows one to observe how TEOA molecules around the Re complex move and how electron transfer occurs.

However, since most solvents used in photocatalytic studies have a high absorption intensity in the THz region, it is difficult to observe Re in TEOA solvent. Thus, the team combined attenuated total reflection spectroscopy and THz time-domain spectroscopy to carry out TR-ATR in the THz region. (Figure 1)

In addition, in order to conduct the ultrafast time-resolved measurements, they combined pump probe spectroscopy with TR-ATR, observing how TEOA molecules moved and how electron transfer occurred on a picosecond-scale timescale during a photocatalytic reaction, a world first. In pump probe spectroscopy, a pump pulse with the wavelength of 400 nm excited a sample and then a probe pulse (THz pulse) was used for probing the sample after an adjustable delay time. As a result, they were able to reveal the intermolecular vibrational mode with a three-step relaxation process on a picosecond timescale after photo-excitation:

Until 9 ps, the temperature of the Re complex sharply increased due to light absorption, inducing heat transfer from Re ions to TEOA molecules, and the excited state was cooled down. (Figure 2 (I))

From 10 to 14 ps, the distance between TEOA molecules and Re ions was reduced by the rotation of TEOA molecules. (Figure 2 (II))

After 14 ps, charge transfer from the TEOA to Re occurred. The distance between these positively charged molecules grew by the repulsive Coulomb force, separating them. (Figure 2 (III))

Professor Kimura from Osaka University says, "The use of THz light allows us to observe the role of the reductant in photocatalytic reaction. TR-ATR spectroscopy in the THz region will help to develop highly efficient photocatalytic reactions. The observation of the relative motion between two molecules and charge dynamics by spectroscopy will assist research on various reaction processes in the fields of biology and chemistry."

Researchers at Tokyo University of Agriculture and Technology (TUAT) in Japan and Mount Allison University in Canada have developed a more efficient method to produce the building blocks needed for antibiotics and cancer treatment drugs.

They published their peer-reviewed results online on August 16 ahead of the September 14 print edition of Chemical Communications, a journal of the Royal Society of Chemistry.

The building blocks the researchers set out to better develop are called polyene substructures.

"Polyene substructures are ubiquitous frameworks in many natural products and pharmaceutical molecules," said Masafumi Hirano, paper author and professor of applied chemistry at TUAT. "Although a lot of attention has been paid to these substructures over the last decade, they are still difficult to prepare."

Current preparation methods are lengthy, with several steps in each phase. The first is what's called iterative cross-coupling, in which two compounds are made to react, resulting in a new compound and excess waste. The new compound is then coupled with another compound and so on, until the desired polyene structure is produced. At each coupling, the compounds must be prepared to react, and, according to Hirano, the time each step takes is not economical.

To correct this inefficient process, Hirano and his team developed a "one-pot" solution. The compounds continuously react, without having to pause each step for preparation.

"This methodology might be compared to an amphibian metamorphosis from egg to tadpole to adult wild toad," Hirano said. "A simple, small compound grows up, one after another, and finally becomes a polyene substructure in the same reaction vessel."

Next, the researchers plan to delve into applying the synthetic building blocks to actual molecules through a flow synthesis process, in which each step in the process triggers the next step with minimal interference. Once the substrates are developed, the researchers need to understand how they can work together to become the molecules that will be used in antibiotics and cancer treatments. The first goal is to develop a library of these types of building blocks, according to Hirano.

"Although current efforts in this research have focused on the chemical engineering side, we need to know each substrate and how it can be applied in this field," Hirano said.

Physicists created a new way to fabricate special kinds of electronic components known as spintronic devices. These high-performance, low-power devices have a promising future, so efficient ways to make them are highly sought after. The new fabrication method is interesting because it uses organic molecules which are relatively easy to configure for different purposes. Layers of molecules could be painted or printed onto metals to create new electronic functions.

In a nutshell, spintronic devices may one day supersede many electronic devices. This is because spintronics is a more efficient way to perform some functions that electronics can at present. Whereas electronic devices depend on a flow of charge in the form of electrons in motion, spintronic devices exploit a different property of electrons known as spin. This is related to the electron's angular momentum and the flow of spin is called a spin current.

There are several challenges to realize useful spintronic devices. Among these are to find ways to induce a spin current and once that's achieved, to imbue spintronic components with useful functions such as the ability to retain data for use as high-speed memory. Research Associate Hironari Isshiki and his team from the University of Tokyo's Institute for Solid State Physics have found a novel and elegantly simple way to tackle both of these complex challenges.

"We successfully demonstrated an efficient conversion of spin current to charge current in a copper sample thanks to a simple coat of 'paint.' This layer is only one molecule thick and comprises an organic substance," said Isshiki. "The device's conversion efficiency is comparable to that of devices made with inorganic metallic materials such as platinum or bismuth. However, in comparison to the inorganic materials, organic materials are much easier to manipulate in order to produce different functionality."

This organic layer is made of a substance called lead(II) phthalocyanine. A spin current injected into the surface covered by the molecule is efficiently converted to a familiar charge current. The researchers experimented with layers of different thickness to see which would be most effective. When the layer was a single molecule thick, the molecules aligned into an ordered arrangement which yielded the most efficient spin to charge current conversion.

"Organic molecules in particular offer spintronic researchers a high degree of design freedom as they are relatively easy to work with. The kinds of functional components we hope to see are things that could be useful in the field of high-performance computing or in low-power devices," explained Isshiki. "The incredibly thin layers required also mean we might one day create flexible devices or even devices you could create with a special kind of printer."

The next steps for Isshiki and colleagues are to explore other configurations of organic layers on conductive materials to realize novel spin functionalities. They also wish to investigate conversion of charge into spin current, the reverse process to that seen in this demonstration. This area of research aims to greatly accelerate the study of spintronics with organic molecules.

DALLAS, Sept. 12, 2019 -- An advanced Magnetic Resonance Imaging (MRI) brain scan analysis in patients with stroke-related, small vessel disease helped predict problems with thinking, memory and even dementia, according to new research published in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

When a stroke or other disease damages tiny blood vessels in the brain, the condition is known as small vessel disease. This condition is the most common cause of thinking problems (planning, organizing information and processing speed) and can even lead to dementia. Although early treatment could help patients at risk, no effective test is available to identify them.

This study evaluated the accuracy of a new MRI analysis technique using diffusion tensor imaging (DTI), in predicting thinking problems and dementia related to small vessel disease. A single scan measured the brain in fine detail to reveal damaged areas. By comparing these images to a healthy person's, researchers were able to classify the brain into areas of healthy versus damaged tissue.

Results showed that participants with the most brain damage were much more likely to develop thinking problems. The analysis also helped predict three-fourths of the dementia cases that occurred during the study.

"We have developed a useful tool for monitoring patients at risk of developing dementia and could target those who need early treatment," said senior author Rebecca A. Charlton, Ph.D., department of psychology at Goldsmiths, University of London, in the United Kingdom.

The study included 99 patients with small vessel disease caused by ischemic stroke, a type of stroke that blocks the blood vessels deep within the brain. Slightly more than one-third were female, average age 68, and most were Caucasian. All participants were enrolled in the St George's Cognition and Neuroimaging in Stroke (SCANS) study from 2007 to 2015 in London.

Participants received the MRI scans annually for three years and thinking tests annually for five years. Eighteen participants developed dementia during the study, with an average time to onset of approximately three years and four months.

This advanced MRI analysis offers a highly accurate and sensitive marker of small vessel disease severity in a single measure that can be used to detect who will and will not go on the develop dementia in a five-year period, noted Charlton.

The healthy brain scans used for comparison were from one individual and may not represent the true range of all healthy brains. In addition, the study's relatively small number of participants all had small vessel disease resulting from one type of stroke, so the results may not apply to people with different forms of the disease.

Researchers at KU Leuven in Belgium have developed a technique to make sheep produce new antibodies simply by injecting the DNA building blocks. This approach is much cheaper and more efficient than producing antibodies industrially and administering them afterwards. The study in animals with a similar size as humans brings us a step closer to the clinical use of antibody gene therapy.

Antibodies are a natural and important part of our immune system. They protect us against foreign intruders in the body, such as viruses or bacteria. Additionally, in the past couple of years, researchers have been developing antibodies in the lab to use as a treatment for infectious diseases or cancer, among others. Most immune therapies, for example, use antibodies. However, their production requires industrial bioreactors that can hold tens of thousands of litres of material. It is a complicated and expensive process, and the resulting medicines can cost up to hundreds of thousands of euros per year.

A team led by Professor Kevin Hollevoet and Professor Paul Declerck of the Laboratory for Therapeutic and Diagnostic Antibodies in collaboration with Dr Nick Geukens of PharmAbs has developed a technique that enables the body itself to produce specific antibodies.

By allowing the body to take over this process,This alternative to the current industrial process can lower the price of antibody therapy drastically. Additionally, the effect of the DNA injection lasts longer, which means that patients would need fewer treatments. As a result, the new technique can increase access to expensive antibody medications.

"Just like other proteins, each antibody has a unique DNA code with building blocks and instructions," explains Hollevoet. "To get this information into the body, we put the desired code in a specially developed plasmid, which is a circular string of DNA. The plasmid functions as a vehicle for the DNA code."

The researchers inject this construction kit into the muscles, followed by a few small electric shocks, comparable to a series of pinpricks. The shocks ensure that the muscle cells can take up the DNA. Next, the cells use the instructions from the code to produce antibodies and send them into the blood, from where they can execute their therapeutic effect.

"There have been several successful studies in the past on mice, including by our research group," says Hollevoet. "But we didn't know whether this approach would work on humans, since they are much larger in size." The researchers decided to test the technique on sheep to build a bridge from the lab to the hospital. Sheep are similar to humans in terms of weight, muscle mass and blood volume. During the development and injection of the DNA construction kit, the researchers tried to mimic a clinical setting, in collaboration with Dr Stéphanie De Vleeschauwer of the KU Leuven Animal Research Center. The sheep's blood tests show that the produced antibodies were present in the body at levels that indicate they could be used as medication. Moreover, the antibodies could be detected in the blood up to almost a year after the injection.

"The fact that this technique also works in larger animals shows that this kind of treatment could be possible for humans. It's a milestone for antibody gene therapy," Declerck says. According to the researchers, sheep can also be used to test potential DNA medications to lower the risk of failure in later clinical trials.

The lab is now working with different research groups and companies to improve the technique. One of the big challenges is to select the most appropriate antibodies. "In principle, we can inject the DNA code of any antibody, but we focus on diseases where this approach can help patients the best," Hollevoet explains. "Currently, we are mostly focused on cancer treatments, among others immune therapy. We also see possibilities for infectious diseases like HIV and the flu, and neurological diseases like Alzheimer's. Even though there are still road blocks on the way to using this treatment in humans, the finish line has never been so close."