Tech

New research led by scientists at Newcastle University, UK reveals a potential revolutionary way to treat eye injuries and prevent blindness - by softening the tissue hosting the stem cells which then helps repair wounds, inside the body.

The team discovered that the simple application of a tissue-softening enzyme, collagenase, prevents the loss of corneal stem cells following an injury and could prevent patients from losing their sight. It offers hope to almost 500,000 people a year who lose their sight due to chemical burns including acid attacks.

The study, published today in Nature Communications and funded by the Medical Research Council shows that keeping corneal stem cells in a soft environment is fundamental for their reproduction, self-renewal, and ability to heal damaged tissue.

Imaging

This discovery was made possible by the development of a sophisticated microscopy technique which enables imaging the physical properties of biological tissues at very high resolutions. Using this technology in collaboration with experts in Photonics from Imperial College London, the team was able to determine that the corneal stem cell niche - the area of tissue in the cornea where stem cells live - is a much softer environment than the rest of the tissue.

The scientists also discovered that stiffening the niche causes stem cells to mature and lose their self-renewing and wound healing properties.

Dr Ricardo Gouveia, Research Fellow at Newcastle University and first author of the paper said: "This study demonstrates a potential new way to treat injuries by changing the stiffness of the natural environment which we have shown changes the behaviour of the adult stem cells. Our imaging approach provides a valuable tool to analyse live cells within the cornea, as well as to further explore new therapies for restoring or even improving their function."

A new look at the cornea

As the outermost layer of the human eye, the cornea has an important role in focusing vision yet many of the processes keeping it transparent and resistant to damage are not well understood. Like skin, the cornea is covered by a multi-layered epithelium forming a barrier to physical harm and invading microorganisms. But unlike the skin, when injury occurs the corneal epithelium is repaired by stem cells clustered in the tissue's periphery, first by quickly dividing in great numbers and then by migrating towards the damaged site as matured epithelial cells in order to seal the wound.

However, this healing process can be compromised when injuries reach the stem cell niche. The research now published has important implications for developing new ways to heal this type of damage.

The director of this study and leader of the Tissue Engineering Lab at Newcastle University, Professor Che Connon, explained: "We can now prove that the cornea becomes stiffer when exposed to injuries such as those caused by what are commonly known as acid attacks, and demonstrate that wound healing is impaired due to stem cells differentiating in response to the stiffening of their otherwise soft niche, and not because they are killed during injury, as previously thought.

"This is an exciting development in the field of corneal biology, and allows us to better understand how vision works. But even more important, it provides us with a new set of strategies to treat eye conditions which were until now inoperable. We call these less invasive strategies Biomechanical Modulation Therapies."

From lab bench to bedside

In the work, the researchers from Newcastle, collaborating with scientists at the University of Missouri, USA, also developed a proof-of-concept therapy to help restore corneal stem cell function and improve tissue regeneration following chemical eye burns.

Using live corneal tissues as a model system, the team recreated the effects of chemical burns. After treating the wounded, stiffened areas of the cornea using small and localised doses of collagenase, a tissue-softening enzyme to restore the stem cell niche, it once again became pliable and able to support stem cells and promote healing. This collagenase formulation has already been approved for related therapeutic applications by both the US Food and Drug Administration and the European Medicine Agency.

Dr Gouveia added: "We show that the topical application of collagenase is safe and effective in restoring the normal stiffness of the cornea and helps tissue regeneration by preventing the differentiation and loss of adult stem cells after such injuries. We were further surprised to discover that the ability for a wound to heal was not directly caused by a lack of stem cells, but instead due to the environment these cells are exposed to. This really makes our therapy revolutionary."

The scientists believe the same technique could be applied to help alleviate the lack of corneas available for transplantation by the almost 5 million people suffering from total blindness due to corneal scarring caused by burns, lacerations, abrasion or disease. In addition, ten million people worldwide are estimated to require surgery for preventing corneal blindness as a result of diseases such as trachoma, an infectious eye disorder affecting many people in developing countries. There is a real and pressing need for new therapies to treat these diseases which are both simple and cheap.

The scientists intend to further expand the research, working with health partners to further test the potential of this study. Professor Connon explained: "Our research shows that corneal stem cells grow better in softer environments. We now want to build on that knowledge and test this method in patients, using biomechanical modulation therapy to re-create suitable environments for corneal stem cells to thrive within the body whenever their original niche is compromised by injury or disease.

"We also think our study is relevant to other scientific and medical fields beyond corneal research, and can help the study, diagnostics, and treatment of diseases such as cancer, where tumour stiffening is a known marker of aggressive cancer cell behaviour and of metastasis."

ANN ARBOR, MI - A curled-up cat, a tail-wagging dog, a chirping parakeet or even a serene goldfish may help older adults cope with mental and physical health issues, according to a new national poll.

While pets come with benefits, they can also bring concerns, and some people may even put their animals' needs ahead of their own health, the poll finds.

In all, 55 percent of adults ages 50 to 80 have a pet, according to the new findings - and more than half of those have multiple pets. More than three-quarters of pet owners say their animals reduce their stress, and nearly as many say pets give them a sense of purpose. But 18 percent also said having a pet or pets puts a strain on their budget.

Two-thirds of all pet owners, and 78 percent of dog owners, said their pet helps them be physically active, according to the new findings from the National Poll on Healthy Aging. The poll is conducted by the University of Michigan Institute for Healthcare Policy and Innovation, and sponsored by AARP and Michigan Medicine, U-M's academic medical center.

For those who reported that their health was fair or poor, pet ownership appeared to offer even more benefits. More than 70 percent of these older adults said their pet helps them cope with physical or emotional symptoms, and 46 percent said their pets help take their mind off of pain.

"We have long known that pets are a common and naturally occurring source of support," says Cathleen Connell, Ph.D., a professor at the U-M School of Public Health who has studied the role of companion animals in older adults' lives. "Although the benefits of pets are significant, social connections and activities with friends and family are also key to quality of life across the lifespan. Helping older adults find low cost ways to support pet ownership while not sacrificing other important relationships and priorities is an investment in overall mental and physical health."

Poll director Preeti Malani, M.D., who has training in caring for older adults, says the poll results indicates a need for physicians and other health care providers to ask older adults about the role of pets in their lives.

"More activity, through dog walking or other aspects of pet care, is almost always a good thing for older adults. But the risk of falls is real for many, and six percent of those in our poll said they had fallen or injured themselves due to a pet," she says. "At the same time, given the importance of pets to many people, the loss of a pet can deal a very real psychological blow that providers, family and friends should be attuned to."

"This study highlights the many physical, psychological, and social benefits that pets can have for older adults," says Alison Bryant, Ph.D., senior vice president of research for AARP. "In recognition of these health benefits, more assisted living facilities today are allowing residents to have pets."

Pet positives

Companionship and social connection were positive side effects of pet ownership for many poll respondents.

In fact, more than half of those who owned pets said they did so specifically to have a companion - and a slightly higher percentage said their pets sleep in bed with them. Sixty-five percent of pet owners said having a pet helps connect them to other people, too.

"Relationships with pets tend to be less complicated than those with humans, and pets are often a source of great enjoyment," says Mary Janevic, Ph.D., M.P.H., an assistant research scientist at the U-M School of Public Health who helped design the poll. "They also provide older adults with a sense of being needed and loved."

Pet problems

Other concerns about pet ownership emerged in the poll results. More than half of pet owners said that having a pet also made it difficult to travel or enjoy activities outside the home.

And one in six said that they put their pet's needs ahead of their own health needs - a figure that was closer to one in four among those with health issues.

"Later life is often a time when people have more freedom to travel, and a long list of things they want to do with their free time, and sometimes having a pet can get in the way,"says Janevic. "For people living on a fixed income, expenses related to health care for pets, and especially pets that have chronic health issues, can be a struggle. Older adults can also develop health problems or disabilities that make pet care difficult."

The non-pet owner perspective

The 45 percent of older adults who said they don't have pets gave many reasons for not keeping a dog, cat, fish, lizard, bird or small mammal around. Among non-pet owners, 42 percent said they didn't want to be tied down. Twenty percent said they didn't have time, and 23 percent gave cost as the reason, while 16 percent said their own allergies, or those of someone in their household, were the reason.

For those who can't own pets due to allergies, budget constraints, housing circumstances or schedules, there's often a need for volunteers at local animal shelters or pet-sitting for friends and family, the researchers say. They note that health care providers and family may even want to recommend these options to older adults who have no pets and wish to have one.

The National Poll on Healthy Aging results are based on responses from a nationally representative sample of 2,051 adults aged 50 to 80 who answered a wide range of questions online. Questions were written, and data interpreted and compiled, by the IHPI team. Laptops and Internet access were provided to poll respondents who did not already have them.

WEST LAFAYETTE, Ind. - Gene editing has been a much sought after and controversial technology. Last month, part of the World Health Organization called for an international registry to track all research into editing the human genome.

Purdue University researchers, including one who was inspired by the cancer death of a close friend, have developed a new technology that could change how gene editing is approached in the future. The research team presents the work on April 4 at the National Meeting of the American Chemical Society in Orlando.

One of the most widely used methods for gene editing is CRISPR-Cas9 technology. The method requires a certain sequence or motif for function that restricts modifications.

"CRISPR can be programmed to cut DNA at specific regions to make precise edits in an organism that can increase sustainable manufacturing, treat disease and even create better crops," said Kevin Solomon, an assistant professor of agricultural and biological engineering, who leads the Purdue research team. "However, it requires a certain sequence for function that restricts modifications to certain regions."

Many diseases in humans, including several types of cancer, are caused by mutations at specific sites in the genome. The Purdue team created a method that uses the protein Argonaute from Natronobacterium gregoryi (NgAgo) and supplied DNA as a guide to enable modification anywhere on the genome, providing new options to potentially improve manufacturing, disease treatment, drug discovery and crop production.

"While there is still work to do, we have shown that these molecular scissors can edit regions of DNA previously inaccessible by current technologies," said 2nd Lt. Michael Mechikoff, a master's student working on the project.

"One of my best friends died from a cancer caused by a genetic variant several years ago," said Kok Zhi Lee, a doctoral student who works on the research team in Solomon's lab. "I always dreamed of a different scenario for my friend - living in an era where genetic engineering is a regular and safe option to correct genetic disorders. With the potential of our technology, I anticipate a future where genetic disease is history for human beings."

The team has worked with the Purdue Research Foundation Office of Technology Commercialization to file a utility patent on the technology. They are looking for partners and others interested in developing and licensing it.

Their work aligns with Purdue's Giant Leaps celebration, acknowledging the university's global advancements in health as part of Purdue's 150th anniversary. It is one of the four themes of the yearlong celebration's Ideas Festival, designed to showcase Purdue as an intellectual center solving real-world issues.

The difficulty in spotting minute amounts of disease circulating in the bloodstream has proven a stumbling block in the detection and treatment of cancers that advance stealthily with few symptoms. With a novel electrochemical biosensing device that identifies the tiniest signals these biomarkers emit, a pair of NJIT inventors are hoping to bridge this gap.

Their work in disease detection is an illustration of the power of electrical sensing - and the growing role of engineers - in medical research.

"Ideally, there would be a simple, inexpensive test - performed at a regular patient visit in the absence of specific symptoms - to screen for some of the more silent, deadly cancers," says Bharath Babu Nunna, a recent Ph.D. graduate who worked with Eon Soo Lee, an assistant professor of mechanical engineering, to develop a nanotechnology-enhanced biochip to detect cancers, malaria and viral diseases such as pneumonia early in their progression with a pin prick blood test.

Their device includes a microfluidic channel through which a tiny amount of drawn blood flows past a sensing platform coated with biological agents that bind with targeted biomarkers of disease in body fluids such as blood, tears and urine - thereby triggering an electrical nanocircuit that signals their presence.

In research recently published in Nano Covergence, Nunna and his co-authors demonstrated the use of gold nanoparticles to enhance the sensor signal response of their device in cancer detection, among other findings.

One of the device's core innovations is the ability to separate blood plasma from whole blood in its microfluidic channels. Blood plasma carries the disease biomarkers and it is therefore necessary to separate it to enhance the "signal to noise ratio" in order to achieve a highly accurate test. The standalone device analyzes a blood sample within two minutes with no need for external equipment.

"Our approach detects targeted disease biomolecules at the femto scale concentration, which is smaller than nano and even pico scale, and is akin to searching for a planet in a galaxy cluster. Current sensing technology is limited to concentrations a thousand times larger. Using a nanoscale platform allows us to identify these lower levels of disease," Nunna says, adding, "And by separating the plasma from the blood, we are able to concentrate the disease biomarkers."

In another recent paper in BioNanoScience, Nunna, Lee and their co-authors detailed their findings on variations in sensitivity based on microfluidic flow.

Nunna is now a postdoctoral research fellow at Harvard Medical School, where he is expanding his expertise in microfluidic platforms, using them in organ-on-the-chip research conducted with Su Ryon Shin, a principal investigator and instructor in the medical school's Department of Medicine who develops 3D-bioprinted organoids - artificial organs composed of cultured cells within structured hydrogels - for medical experimentation.

"I'm primarily responsible for developing the microfluidic devices that will automate the process of bioprinting 3D organs that will be incorporated on a chip for a number of purposes. I'm tasked, for example, with developing an automated platform for long-term drug efficacy and toxicity analysis to track liver cancer and cardiac biomarkers. I'll be integrating the microfluidic biosensor with the liver cancer- and heart-on-a-chip model for continuous monitoring," he says.

By measuring the biomarker concentrations secreted from drug-injected 3D-bioprinted organs, we can study drug effects on several organs without harming a live patient. Creating artificial organs allows us to experiment freely."

Down the road, he adds, the work at Harvard could potentially be applied in regenerative medicine. "The goal is to develop fully functional 3D-bioprinted organoids and clinically relevant 3D tissues to address the issue of donor shortages in transplantation."

Nunna says his research at Harvard Medical School will expand his knowledge of programmable microfluidics and precise electrochemical sensing techniques, which will in turn help him advance his biochip technology. The goal is a simple, standard assay for cancer diagnosis that avoids conventional, complex diagnostic steps.

Lee and Nunna have been working with oncologists at Weill Cornell Medicine and Hackensack Medical Center to identify clinical applications. As currently designed, the device would provide both qualitative and quantitative results of cancer antigens in blood samples, providing information on the presence and the severity of the cancer. Their next step, he says, will be to expand the platform to detect multiple diseases using a single blood sample obtained with a pin prick.

"Although healthcare technology is considered to be a fast-evolving technology, there are still many unmet needs that need to be addressed. Diagnosing potentially deadly diseases at the early stages is the key to saving lives and improving patient treatment outcomes," he says, adding, "There is a huge need for healthcare technology, including a universal diagnostic platform that can provide instant results at the physician's office and other point-of-care settings."

Nunna is the co-founder and chief research scientist for Abonics, Inc., a startup formed by Lee to commercialize their device. He is named as a co-inventor with Lee on three published biochip patents and six additional patents that are now under review by the U.S. Patent and Trademark Office. Their technology has won financial backing from the National Science Foundation I-Corps program and the New Jersey Health Foundation (NJHF), a not-for-profit corporation that supports top biomedical research and health-related education programs in New Jersey.

"As we know, early detection can improve treatment outcomes for patients significantly," explained George F. Heinrich, M.D., vice chair and CEO of NJHF, in announcing the award. "Currently, doctors rely on diagnostic devices requiring a minimum of four hours of sample preparation through centralized diagnostic centers rather than their local offices."

In 2017, Nunna received the "Best Design in Healthcare Innovations and Point-of-Care Innovations Award" at the Healthcare Innovation and Point-of-Care Technologies conference from the Engineering in Medicine and Biology Society, held at the National Institute of Health headquarters in Bethesda, MD. That same year, the technology received the national innovation award at the TechConnect World Innovation Conference and Expo, an annual gathering of technology transfer offices, companies, and investment firms who meet to identify promising technologies from across the globe.

BINGHAMTON, N.Y. - Researchers at Binghamton University, State University of New York, have developed skin-inspired electronics to conform to the skin, allowing for long-term, high-performance, real-time wound monitoring in users.

"We eventually hope that these sensors and engineering accomplishments can help advance healthcare applications and provide a better quantitative understanding in disease progression, wound care, general health, fitness monitoring and more," said Matthew Brown, a PhD student at Binghamton University.

Biosensors are analytical devices that combine a biological component with a physiochemical detector to observe and analyze a chemical substance and its reaction in the body. Conventional biosensor technology, while a great advancement in the medical field, still has limitations to overcome and improvements to be made to enhance their functionality. Researchers at Binghamton University's Intimately Bio-Integrated Biosensors lab have developed a skin-inspired, open-mesh electromechanical sensor that is capable of monitoring lactate and oxygen on the skin.

"We are focused on developing next-generation platforms that can integrate with biological tissue (e.g. skin, neural and cardiac tissue)," said Brown. Under the guidance of Assistant Professor of Biomedical Engineering Ahyeon Koh, Brown, master's students Brandon Ashely and Youjoong Park, and undergraduate student Sally Kuan designed a sensor that is structured similarly to that of the skin's micro architecture. This wearable sensor is equipped with gold sensor cables capable of exhibiting similar mechanics to that of skin elasticity.

The researchers hope to create a new mode of sensor that will meld seamlessly with the wearer's body to maximize body analysis to help understand chemical and physiological information.

"This topic was interesting to us because we were very interested in real-time, on-site evaluation of wound healing progress in a near future," said Brown. "Both lactate and oxygen are critical biomarkers to access wound-healing progression."

They hope that future research will utilize this skin-inspired sensor design to incorporate more biomarkers and create even more multifunctional sensors to help with wound healing. They hope to see these sensors being developed incorporated into internal organs to gain an increased understanding about the diseases that affect these organs and the human body.

"The bio-mimicry structured sensor platform allows free mass transfer between biological tissue and bio-interfaced electronics," said Koh. "Therefore, this intimately bio-integrated sensing system is capable of determining critical biochemical events while being invisible to the biological system or not evoking an inflammatory response."

A long-nosed fly from the Jurassic of Central Asia, reported by Russian paleontologists, provides new evidence that insects have started serving as pollinators long before the emergence of flowering plants. Equipped with a proboscis twice the length of the body, this fly predates the first angiosperms by about 40-45 million years. This suggests that insect pollination began to evolve in association with ancient gymnosperms.The results of the study are published in Gondwana Research.

Archocyrtus kovalevi is only known as a single compression fossil found in the Late Jurassic rocks in Southern Kazakhstan. The fossil, estimated to be about 160 million years in age, first came into light in 1996, but its original description did not contain any photos. It is no wonder that nobody believed at first that this fly had evolved a proboscis of such proportions so early in time. Despite not having seen the specimen itself, skeptics said that the long structure next to the fly's body was not a genuine proboscis, but must be a piece of plant or other stray object. As a result, a remarkable finding fell into oblivion for more than 20 years.

To dig up the truth about the enigmatic fossil, paleontologists from Borissiak Paleontological Institute (Moscow) reexamined it using modern microscopic techniques and element distribution analysis. This allowed them to confirm the presence of a long proboscis, which has an easily discernible food canal and is identical to mouthparts of living long-proboscid flies in all other respects. Measuring 12 mm long, mouthparts of A. kovalevi is 1.8 times longer than the body. It means that this tiny fly ranks first among all the Mesozoic insects in having the longest proboscis relative to body size.

A. kovalevi is the earliest fossil record of extant family Acroceridae, or small-headed flies. Nowadays, there are a few species of small-headed flies with a proboscis longer than body found in the Americas and South Africa. The present-day members of Acroceridae use their oversized proboscis to draw nectar from long tubular flowers, acting as pollinators in the process. The unusual thing is that A. kovalevi existed at the time when not a single flower was blooming. The first flowering plants emerged much later, in the Early Cretaceous, and at first had small, inconspicuous flowers. So what was the proboscis of A. kovalevi used for?

"There is a well-known story about Charles Darwin, who famously predicted the existence of a pollinating moth with a long proboscis after seeing the deep nectar spur of the Madagascar orchid. We have to argue the other way round and conclude from the ancient long-nosed fly that we see to a plant which it may have pollinated", said Alexander Khramov, the first author of the study and a senior researcher at Borissiak Paleontological Institute.

Luckily, researchers did not need to go too far in their guesses. Dozens of cones of the plant called Williamsoniella karataviensis have been collected from the same strata as the fly. This plant belongs to Bennettitales, an extinct group of the Mesozoic gymnosperms, many of which had showy, flower-like reproductive organs, and on this ground scientists have long suspected them to be insect pollinated. W. karataviensis fits into this picture perfectly. It has bisexual cones consisting of twelve petal-like bracts (modified leaves) arched over the ovules (precursors of seeds). Like modern Gnetales, a relict group of gymnosperms pollinated by insects, including flies, ovules of W. karataviensis could have produced sugary pollination drops.

The depth of the cones of W. karataviensis roughly matches the length of proboscis of A. kovalevi, so the pieces of the puzzle come together: small-headed flies first evolved an extremely long proboscis to get an access to the sugary secretions hidden deep in the cones of ancient gymnosperms. It is highly probable that they did pollination work in return for sweet reward. It follows that the foundation of pollination mutualism between plants and insects had been laid long before the first true flowers adorned the Earth. When the Mesozoic gymnosperms left the stage, Acroceridae and probably some other long-proboscid insects offered their pollinating services to newly emerged flowering plants.

A cancer cell is like a racecar, speeding through the process of cellular replication. But it has to stop at the G2M cell cycle checkpoint, where a race inspector called Wee1 checks it over for damage - cells with intact DNA can continue, while cells with damaged DNA have to stick around for repairs. The wait is worth it - there are curves ahead, and beyond the G2M checkpoint, cells with damaged DNA explode against the wall of "mitotic catastrophe." But the thing is, we want cancer cells to explode; we would rather they speed through the G2M checkpoint without a Wee1 inspection and hit the wall of mitotic catastrophe.

A University of Colorado Cancer Center study presented at the American Association for Cancer Research (AACR) Annual Meeting 2019 suggests a way to ensure that cancer cells with damaged DNA fly past G2M to their doom: Blindfold the race inspector. By inhibiting the action of Wee1, cancer cells blow right through the G2M checkpoint and are doomed by their damaged DNA to mitotic catastrophe.

The Wee1 inhibitor adavosertib is used in a number of previous and ongoing clinical trials. However, the drug's effectiveness has overall been promising but not perfect. The goal of the current study was to test drugs in combination with adavosertib that might magnify its effect. Specifically, the study hoped to find new combinations against pancreatic cancer, which carries a prognosis of less than 7 percent 5-year survival.

"The way the grant was focused was to utilize the list of the drugs in the NCI's Cancer Therapy Evaluation Program (CTEP) and figure out what drugs might work together with adavosertib against pancreatic tumors," says Todd Pitts, PhD, investigator at CU Cancer Center and assistant research professor in the CU School of Medicine Division of Medical Oncology.

More broadly, the work of the Pitts lab is at the cutting edge of a developing strategy against cancer, namely the manipulation of cells' ability to repair damaged DNA. Commonly, DNA damage repair fixes mutations that could cause cancer. In other words, "DNA damage repair is usually a good thing," Pitts says. But when the cells being repaired are cancer cells, the "good" outcome switches from repair to destruction.

Pitts and colleagues including study first author Sarah Hartman, MS, ended up testing the following drugs/combinations: adavosertib, irinotecan, navitoclax, capecitabine, adavosertib + irinotecan, or adavosertib + navitoclax, adavosertib + capecitabine. After using cell cultures to determine optimal doses, the researchers tested these drugs and drug combinations on PDX models of pancreatic cancer - basically, human tumors grown on mice.

The most successful combinations were adavosertib with irinotecan, navitoclax or capecitabine.

"The Wee1 inhibitor and navitoclax have overlapping toxicities, so we don't believe that combination will move forward clinically. But the irinotecan and capecitabine combos could move forward," Pitts says.

In fact, the group recently submitted a letter of intent to start a clinical trial of combination adavosertib with capecitabine. "There will always be some toxicity from a Wee1 inhibitor, but capecitabine is very well tolerated, so we think adavosertib with capecitabine would be a well-tolerated combination," Pitts says.

Combining drugs with sex is common regardless of gender or sexual orientation, reveals new research by UCL and the Global Drug Survey into global trends of substance-linked sex.

The findings, published today in The Journal of Sexual Medicine, revealed that alcohol, cannabis, MDMA and cocaine are the drugs most commonly combined with sex.

Respondents from the United Kingdom were the most likely to combine drugs with sex, compared with the US, other European countries, Australia and Canada.

"While using drugs in combination with and to specifically enhance the sexual experience tends to be associated with gay and bisexual men, we found that in our sample, men and women of all sexual orientations engaged in this behaviour. However, differences between groups did emerge," said the study's lead author, Dr Will Lawn (UCL Psychology & Language Sciences).

"Harm reduction messages relating to substance-linked sex in general should therefore not only be targeted towards gay and bisexual men, as they are relevant to all groups."

As part of the Global Drug Survey, roughly 22,000 people responded to online questions about which drugs they used in combination with sex, in addition to questions about whether they used drugs to specifically enhance their sexual experience, and how these drugs affect the sexual experience.

Alcohol, cannabis, MDMA and cocaine were most commonly used, while GHB/GBL and MDMA were rated most favourably. For instance, MDMA increased 'emotionality/intimacy' the most, while GHB/GBL increased 'sexual desire' the most.

While people of all genders and sexual orientations reported engaging in substance-linked sex, gay and bisexual men were more likely to have done so; homosexual men were 1.6 times as likely as heterosexual men to have used drugs with the specific intent of enhancing the sexual experience in the last year.

Drugs typically considered as 'chemsex' drugs - methamphetamine, mephedrone and GHB/GBL - were more commonly used by gay and bisexual men in combination with sex, which the researchers say highlights the continued need for certain targeted harm reduction messages.

As the survey respondents were self-selecting rather than a representative sample, the researchers say their estimates of prevalence will be substantially larger than the general population. However, relative differences between groups are expected to be reliable.

While country of residence was not asked specifically, currency was used as a proxy. This revealed that those from the UK were more likely to have combined all drugs, except for cannabis, with sex; this trend was particularly strong for mephedrone.

The researchers say that understanding how and why people use drugs is essential if we are to deliver harm reduction messages that are in touch with peoples' lived experience.

"By engaging with your audience and accepting that drugs provide pleasure as well as harms, you can deliver harm reduction messages in a more trustworthy and nuanced manner," said Dr Lawn.

Senior author Professor Adam Winstock, founder and director of the Global Drug Survey added: "Our study is by far the largest to date to investigate the relationships between sex and drugs. Previous studies have rarely compared men and women, and people of different sexual orientations.

"Furthermore, by appreciating how different drugs affect sex we can tailor our harm reduction messages. These pragmatic messages can save lives."

Research led by Professor Ton Peijs of WMG at the University of Warwick and Professor Cees Bastiaansen at Queen Mary University of London, has devised a processing technique that can create transparent polythene film that can be stronger as aluminium but at a fraction of the weight, and which could be used use in glazing, windscreens, visors and displays in ways that add strength and resilience while reducing weight.

In a new research paper entitled "Glass-like transparent high strength polyethylene films by
tuning drawing temperature." Published online today - 1st April 2019 - in the Journal Polymer, the authors show that after carefully selecting the type polythene and by tuning the temperature during the creation of oriented polythene films a balance can be created that produces a highly useful and lightweight transparent material with a significant strength and resilience approaching, and in some ways, exceeding that of metals.

Previously anyone looking to replace heavy and often brittle glasses with a transparent plastic have looked at conventional transparent plastics like polycarbonate (PC) and poly(methylmethacrylate) (PMMA) both of which possess relatively unsatisfactory mechanical performance compared to an engineering material like aluminium.

Current methods of creating high strength plastic films such as hot-drawing of high-density polyethylene (HDPE) can lead to materials that can compete or even out-perform traditional engineering materials like metals.

"The microstructure of polymers before drawing very much resembles that of a bowl of cooked spaghetti or noodles, while after stretching or drawing the molecules become aligned in a way similar to that of uncooked spaghetti, meaning that they can carry more load" explains Yunyin Lin, a PhD student in Professors Peijs and Bastiaansen's team.

However, drawn polythene materials normally have an opaque appearance due to defects and voids introduced by the drawing process, limiting applications where both mechanical properties and optical transparency are required.

Some success has recently been achieved by using highly specific additives in hot-drawn HDPE materials that can then produce 90% transparency while giving high strength. However, the research team led by Professors Peijs and Bastiaansen have now developed a new post-manufacturing technique for HDPE that endows strength and resilience while preserving transparency without using additives.

The researchers took HDPE polythene sheets and drew out these sheets at a range of temperatures below the melting temperature of HDPE. By tuning the drawing temperature they could achieve a transparency of 90% in the visible range. However, the best balance between strength and transparency was achieved at drawing temperatures between 90 and 110 degrees centigrade.

Professor Ton Peijs of WMG at the University of Warwick said:

"We expect greater polymer chain mobility at these high drawing temperatures to be responsible for creating fewer defects in the drawn films, resulting in less light scattering by defects and therefore a higher clarity."

The highly transparent films possess a maximum resilience or Young's Modulus of 27 GPa and a maximum tensile strength of 800 MPa along the drawing direction, both of which are more than 10 times higher than those of PC and PMMA plastics. For comparison, aluminium has a Young's Modulus of 69 GPa and aerospace grade aluminium alloy can have tensile strengths up to around 500 MPa. However, polythene has a density of less than 1000 kg/m3 while aluminium has a density of around 2700 kg/m3, meaning that on weight basis these high strength transparent polymer films can outperform such metals.

Professor Ton Peijs in WMG at the University of Warwick concludes that:

"Our results showed that a wide processing window ranging from 90 °C to 110 °C can be used to tailor the required balance between optical and mechanical performance. It is anticipated that these lightweight, low-cost, highly transparent, high strength and high stiffness HDPE films can be used in laminates and laminated composites, replacing or strengthening traditional inorganic or polymeric glass for applications in automotive glazing, buildings, windshields, visors, displays etc."

AURORA, Colo. (April 1, 2019) - While women outnumber men as Ob/Gyn practitioners, they still make significantly less money and the pay gap extends to subspecialties like reproductive endocrinology and infertility (REI), according to researchers at the University of Colorado Anschutz Medical Campus.

"It's interesting that the Ob/Gyn field is dominated by women and yet this gender inequality in pay persists," said the study's senior author Malgorzata Skaznik-Wikiel, MD, assistant professor of obstetrics and gynecology at the University of Colorado School of Medicine. "Why the discrepancy?"

The study was published on-line this month in the journal Fertility and Sterility.

It showed that even after adjusting for variables like hours worked, years in practice, location, academic vs. private practice, female reproductive endocrinology and infertility subspecialists make on average $67,000 less than male REIs per year.

Pay inequity among physicians in well-documented. According to Doximity, an online social network for health care professionals, women doctors make about 27.7 percent less than male physicians or about $105,000.

A recent commentary in the journal Obstetrics and Gynecology noted that 82 percent of those going into Ob/Gyn were women, yet the field is the fourth worst of 18 specialties in pay inequity among the sexes.

Skaznik-Wikiel and her colleagues sent surveys to 796 board-certified or board-eligible Society for Reproductive Endocrinology and Infertility members. Of those, 215 responded, an above average response for such surveys.

The study noted that although women were more likely to practice less than five days per week, there were no significant differences in the number of hours they spent per week seeing patients, doing research or being involved in other academic activities.

The researchers reviewed a number of reasons given for the pay gap - women working fewer hours, taking more personal leave, practicing in specialties that pay less or practicing in academia rather than privately.

Yet they found little to substantiate these suggestions.

For example, the study said it's unlikely that a woman taking more personal leave, like maternity leave, would affect a base salary. Also, they said, more and more men are taking paternity leave as well.

One possible culprit is `salary compression.' That's when the market rate for a job outpaces pay increases for those already in those positions. New hires may get bigger salaries.

"There is some evidence that men switch jobs more often than women and sometimes new jobs will pay more to attract new employees," Skaznik-Wikiel said.

She also said women are often reluctant to negotiate hard over salary for fear of being seen as overly aggressive, traits many do not associate with men who do the same thing.

Ultimately, Skaznik-Wikiel said, there is no good reason for the discrepancy.

"The first step in addressing the gender gap is acknowledging it exists," she said. "Ignorance of this issue is no longer acceptable."

The second step is opening a frank and honest discussion about income, salary negotiations and implementation of academic institutional and private practice policies addressing potential gender biases, the study said.

Salaries, raises and bonuses should be more transparent, said Skaznik-Wikiel.

"Women also need to step into mentorship roles now more than ever," she said. "An opportunity exists for practitioners in the field of obstetrics and gynecology and its subspecialties to lead by example in establishing new transparent norms and better policies that create an environment of equity in pay."

Cyclists in London should take a different route back home during evening peak-time hours to avoid breathing in harmful black carbon from vehicles, suggests a new collaborative air pollution study from the University of Surrey's Global Centre for Clean Air Research (GCARE), jointly with University of São Paulo (Brazil) and University of Twente (Netherlands).

According to the Department of Transport, London has just over three million licensed vehicles - 2.7 million of which are cars. In the Greater London area, 35 per cent of all trips are made by car and 730,000 cycling trips are made every day - a number that has grown by 154 per cent since 2000.

In a study published by the Journal of Transport Geography, scientists who developed this collaborative study looked at the black carbon levels cyclists are likely to be exposed to on heavily trafficked main routes in three major cities - London (travelling to Liverpool Street), Rotterdam (travelling to Rotterdam Station) and São Paulo (travelling to Paulista Avenue). The scientists then compared this information with black carbon exposure on alternative routes between the same origin and destination that feature parks, waterways and other green infrastructure.

Overall, the results showed that the main routes in London and São Paulo exposed cyclists to higher concentrations of black carbon compared with alternative routes. In Rotterdam, concentration levels on main and alternative routes were similar.

The results also found that cyclists were exposed to twice as much black carbon levels on main routes in São Paulo compared to London and Rotterdam. Interestingly, Londoners cycling home on the main route during the evening commute were exposed to more pollutants than those who took the same route in the morning, and twice as much black carbon than those who took the alternative route.

Professor Prashant Kumar, Director of GCARE at the University of Surrey, said: "While it is common sense to conclude that cyclists are at risk of potentially harmful exposure levels of black carbon, our study provides further evidence that cyclists should plan alternative routes during specific times. A slower, cleaner route home could make a dramatic impact on your exposure to harmful black carbon.

"These findings should be considered when urban planners establish new cycle networks by increasing, as much as possible, the distance between the road and the cycle ways. This evidence also direct decision makers to seriously invest in green infrastructure throughout our major cities, as there is mounting evidence that these could provide the best line of defence against road pollution in near-road environments."

Professor Maria de Fatima from the University of São Paulo added: "As the use of vehicles continues to grow in Latin America, especially in São Paulo, it is important that we continue to gather evidence so we can understand what impact this use of mostly biofuel-blended diesel fuelled vehicles has on our local environment, our personal health and the wellbeing of our planet."

Red blood cells are amazing. They pick up oxygen from our lungs and carry it all over our body to keep us alive. The hemoglobin molecule in red blood cells transports oxygen by changing its shape in an all-or-nothing fashion. Four copies of the same protein in hemoglobin open and close like flower petals, structurally coupled to respond to each other. Using supercomputers, scientists are just starting to design proteins that self-assemble to combine and resemble life-giving molecules like hemoglobin. The scientists say their methods could be applied to useful technologies such as pharmaceutical targeting, artificial energy harvesting, 'smart' sensing and building materials, and more.

A science team did this work by supercharging proteins, which means that they changed the subunits of proteins, the amino acids, to give the proteins an artificially high positive or negative charge. Using proteins derived from jellyfish, the scientists were able to assemble a complex sixteen protein structure composed of two stacked octamers by supercharging alone, findings that were reported in January of 2019 in the journal Nature Chemistry.

The team then used supercomputer simulations to validate and inform these experimental results. Supercomputer allocations on Stampede2 at the Texas Advanced Computing Center (TACC) and Comet at the San Diego Supercomputer Center (SDSC) were awarded to the researchers through XSEDE, the Extreme Science and Engineering Discovery Environment funded by the National Science Foundation (NSF).

"We found that by taking proteins that don't normally interact with each other, we can make copies that are either highly positively or highly negatively charged," said study co-author Anna Simon, a postdoctoral researcher in the Ellington Lab of UT Austin. "Combining the highly positively and negatively charged copies, we can make the proteins assemble into very specific structured assemblies," Simon said. The scientists call their strategy 'supercharged protein assembly,' where they drive defined protein interactions by combining engineered supercharged variants.

"We exploited a very well-known and basic principle from nature, that opposite charges attract," added study co-author Jens Glaser. Glaser is an assistant research scientist in the Glotzer Group, Department of Chemical Engineering at the University of Michigan. "Anna Simon's group found that when they mix these charged variants of green fluorescent protein, they get highly ordered structures. That was a real surprise," Glaser said.

The stacked octamer structure looks like a braided ring. It's composed of 16 proteins - two intertwined rings of eight that interact in very specific, discreet patches. "The reason why it's so hard to engineer proteins that interact synthetically is that making these interacting patches and having them all line up right such that they'll allow the proteins to assemble into bigger, regular structures is really hard," explained Simon. They got around the problem by adding many positive and negative charges to engineer variants of green fluorescent protein (GFP), a well-studied 'lab mouse' protein derived from the Aequorea victoria jellyfish.

The positively charged protein, which they called cerulean fluorescent protein (Ceru) +32, had additional opportunities to interact with the negatively charged protein GFP -17. "By giving these proteins all these opportunities, these different places where they could potentially interact, they were able to choose the right ones," Simon said. "There were certain patterns and interactions that were there, available, and energetically favored, that we didn't necessarily predict beforehand that would allow them to assemble into these specific shapes."

To get the engineered charged fluorescent proteins, Simon and co-authors Arti Pothukuchy, Jimmy Gollihar, and Barrett Morrow encoded their genes, including a chemical tag used for purification on portable pieces of DNA called plasmids in E. coli, then harvested the tagged protein that E. coli grew. The scientists mixed the proteins together. They initially thought the proteins might just interact to form large, irregularly structured clumps. "But then, what we kept on seeing was this weird, funny peak around 12 nanometers, that was a lot smaller than a big clump of protein, but significantly bigger than the single protein," Simon said.

They measured the size of the particles that formed using a Zetasizer instrument at the Texas Materials Institute of UT Austin, and verified that the particles contained both cerulean and GFP proteins Förster Resonance Energy Transfer (FRET), which measures the energy transfer between different colored fluorescent proteins produce fluorescence in response to different energies of light to see if they are close together. Negative stain electron microscopy identifed the specific structure of the particles, conducted by the group of David Taylor, assistant professor of molecular biosciences at UT Austin. It showed that the 12 nm particle consisted of a stacked octamer composed of sixteen proteins. "We found that they were these beautifully shaped flower-like structures," Simon said. Co-author Yi Zhou from Taylor's group of UT Austin increased the resolution even further using cryo-electron microscopy to reveal atomic-level details of the stacked octamer.

Computational modeling refined the measurements of how the proteins were arranged into a clear picture of the beautiful, flower-like structure, according to Jens Glaser. "We had to come up with a model that was complex enough to describe the physics of the charged green fluorescent proteins and present all the relevant atomistic details, yet was efficient enough to allow us to simulate this on a realistic timescale. With a fully atomistic model, it would have taken us over a year to get a single simulation out of the computer, however fast the computer was," Glaser said.

They simplified the model by reducing the resolution without sacrificing important details of the interactions between proteins. "That's why we used a model where the shape of the protein is exactly represented by a molecular surface, just like the one that's measured from the crystallographic structure of the protein," Glaser added.

"What really helped us turn this around and improve what we were able to get out of our simulations was the cryo-EM data," said Vyas Ramasubramani, a graduate student in chemical engineering at the University of Michigan. "That's what really helped us find the optimal configuration to put into these simulations, which then helped us validate the stability arguments that we were making, and hopefully going forward make predictions about ways that we can destabilize or modify this structure," Ramasubramani said.

The scientists required lots of compute power to do the calculations on the scale that they wanted.

"We used XSEDE to basically take these huge systems, where you have lots of different pieces interacting with each other, and calculate all of this at once so that when you start moving your system forward through some semblance of time, you could get an idea for how it was going to evolve on somewhat real timescales," Ramasubramani said. "If you tried to do the same kind of simulation that we did on a laptop, it would have taken months if not years to really approach understanding whether or not some sort of structure would be stable. For us, not being able to use XSEDE, where you could use essentially 48 cores, 48 compute units all at once to make these calculations highly parallel, we would have been doing this much slower."

The Stampede2 supercomputer at the TACC contains 4,200 Intel Knights Landing and 1,736 Intel Skylake X compute nodes. Each Skylake node has 48 cores, the basic unit of a computer processor. "The Skylake nodes of the Stampede2 supercomputer were instrumental in achieving the performance that was necessary to compute these electrostatic interactions that act between the oppositely-charged proteins in an efficient manner," Glaser said. "The availability of the Stampede2 supercomputer was at just the right point in time for us to perform these simulations."

Initially, the science team tested their simulations on the Comet system at the SDSC. "When we were first figuring out what kind of model to use and whether this simplified model would give us reasonable results, Comet was a great place to try these simulations," Ramasubramani said. "Comet was a great testbed for what we were doing."

Looking at the bigger scientific picture, the scientists hope that this work advances understanding of why so many proteins in nature will oligomerize, or join together to form more complex and interesting structures.

"We showed that there doesn't need to be a very specific, pre-distinguished set of plans and interactions for these structures to form," Simon said. "This is important because it means that maybe, and quite likely we can take other sets of molecules that we want to make oligomerize and generate both positively charged and negatively charged variants, combine them, and have specifically ordered structures for them."

Natural biomaterials like bone, feathers, and shells can be tough yet lightweight. "We think supercharged protein assembly is an easier way to develop the kind of materials that have exciting synthetic properties without having to spend so much time or having to know exactly how they're going to come together beforehand," Simon said. "We think that will accelerate the ability to engineer synthetic materials and for discovery and exploration of these nanostructured protein materials."

For the estimated 100 million U.S. adults and children living with nonalcoholic fatty liver disease (NAFLD), whether or not they have liver cirrhosis, or scarring, is an important predictor for survival. Yet it's difficult and invasive to detect liver cirrhosis before it is well advanced. In an effort to quickly and easily identify people at high risk for NAFLD-cirrhosis, researchers in the NAFLD Research Center and Center for Microbiome Innovation at University of California San Diego identified unique patterns of bacterial species in the stool of people with the condition.

The study publishes March 29, 2019 in Nature Communications.

"If we are better able to diagnose NAFLD-related cirrhosis, we will be better at enrolling the right types of patients in clinical trials, and ultimately will be better equipped to prevent and treat it," said senior author Rohit Loomba, MD, professor of medicine in the Division of Gastroenterology at UC San Diego School of Medicine, director of the NAFLD Research Center and a faculty member in the Center for Microbiome Innovation at UC San Diego. "This latest advance toward a noninvasive stool test for NAFLD-cirrhosis may also help pave the way for other microbiome-based diagnostics and therapeutics, and better enable us to provide personalized, or precision, medicine for a number of conditions."

The precise cause of NAFLD is unknown, but both diet and genetics play substantial roles. Up to 50 percent of obese people are believed to have NAFLD, and people with a first-degree relative with NAFLD are at increased risk for the disease themselves.

In a previous proof-of-concept study of patients with biopsy-proven NAFLD, Loomba and colleagues found a gut microbiome pattern that distinguished mild/moderate NAFLD from advanced disease, allowing them to predict which patients had advanced disease with high accuracy. In this latest study, Loomba's team wanted to know if a similar stool-based "read-out" of what is living in a person with NAFLD's gut might provide insight into his or her cirrhosis status.

The researchers analyzed the microbial makeup of stool samples from 98 people known to have some form of NAFLD and 105 of their first-degree relatives, including some twins. They did this by sequencing the 16S rRNA gene, a genetic marker specific for bacteria and their relatives, archaea. The 16S rRNA sequences serve as "barcodes" to identify different types of bacteria and the relative amounts of each, even in a mixed sample like stool.

The researchers first noticed that people who share a home also tended to share similar microbial patterns in their gut microbiomes, further validating several previous studies. In addition, they observed that people with extreme forms of NAFLD had less diverse and less stable gut microbiomes.

Then the team identified 27 unique bacterial features unique to the gut microbiomes, and thus stool, of people with NAFLD-cirrhosis. The researchers were able to use this noninvasive stool test to pick out the people with known NAFLD-cirrhosis with 92 percent accuracy. But more importantly, the test allowed them to differentiate the first-degree relative with previously undiagnosed NAFLD-cirrhosis with 87 percent accuracy. The results were confirmed by magnetic resonance imaging (MRI).

While Loomba estimates that a stool-based microbiome diagnostic might cost $1,500 if it were on the market today, he predicts that cost will lower to less than $400 in the next five years due to advances in genomic sequencing and analysis technologies.

The researchers caution that so far this new diagnostic approach has only been tested in a relatively small patient group at a single, highly specialized medical center. Even if successful, a stool-based test for NAFLD wouldn't be available to patients for at least five years, they said. Loomba also pointed out that while a distinct set of microbial species may be associated with advanced NAFLD-cirrhosis, this study does not suggest that the presence or absence of these microbes causes NAFLD-cirrhosis or vice versa.

Atlanta-March 29, 2019-New research demonstrating the clinical utility of Bio-Rad's Droplet Digital PCR (ddPCR) powered liquid biopsy will be presented this week during the 2019 American Association for Cancer Research (AACR) Annual Meeting in Atlanta, March 29-April 3. Many of the studies rely on the sensitivity, speed, and cost-effectiveness of ddPCR technology to measure blood-based tumor biomarkers in a reproducible way.

Cited in more than 900 liquid biopsy publications, ddPCR technology is often employed by cancer researchers and oncologists to track disease progression and determine therapy response, but it is yet to be ascertained whether changing therapies based on this timely information translates to improved patient outcomes. A large phase 3 study currently underway is addressing that question by analyzing circulating tumor DNA (ctDNA) in plasma using ddPCR technology. Below we highlight this study and other notable research that will be presented during this year's AACR Annual Meeting.

Liquid biopsy could be superior to tissue biopsy in predicting breast cancer therapy response

Sara Tolaney, MD, MPH, of the Dana-Farber Cancer Institute, and her collaborators used ddPCR technology in their investigation of the benefits of tracking drug-resistance mutations in the ctDNA of patients with hormone receptor-positive metastatic breast cancer.

In the phase 3 study, researchers measured mutations in two genes (PIK3CA and ESR1) implicated in drug resistance. Their study included 334 plasma samples and 434 archival tissue samples from 669 patients treated with either fulvestrant alone or fulvestrant plus abemaciclib. The researchers found a correlation between the presence of PIK3CA and ESR1 mutations and response to abemaciclib in ctDNA, but not in tissue samples. They also found that while the addition of abemaciclib was beneficial for all patients, those with PIK3CA and ESR1 mutations benefited more.

"These findings lend support to the use of ctDNA and liquid biopsies to identify molecular alterations that could help inform treatment choices," Tolaney said.

The next step is validating these data in prospective clinical trials.

This poster (abstract #4458) will be presented on Tuesday, April 2, 3-5 PM in Room B312.

ctDNA could be a predictor of surgery success for malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive, but relatively rare, tumor associated with asbestos exposure. Most patients with MPM are over 70 years old, so surgery can be risky and may not improve outcomes. Luke Martinson, PhD, of the University of Leicester, and his colleagues conducted a proof-of-principle study to understand the potential use of ctDNA as a prognostic biomarker for surgical success for these patients.

The scientists compared genetic differences between tumor and normal tissue in 11 patients with MPM and developed a ddPCR assay that could detect MPM-specific ctDNA. Next, they tested patient blood samples collected before surgery. Results showed that patients with MPM-specific ctDNA had a worse prognosis after surgery.

"Detection of ctDNA requires highly sensitive methods and ddPCR technology was ideally suited to help us answer the question of whether or not the ctDNA status was informative of patient survival," said Martinson.

The researchers hope to confirm the preliminary findings with a larger cohort. If validated, ctDNA would represent one of the few known prognostic markers for MPM.

This poster (abstract #1349) will be presented on Monday, April 1, 8 AM-12 PM in Section 18.

Detecting therapy resistance in HER2-negative breast cancer

Continuing work presented at last year's American Society of Clinical Oncology annual meeting, researchers are examining whether changing therapies may be effective for patients with advanced breast cancer when mutations are detected in their ctDNA. This is the first large-scale effort to monitor resistance mutations and personalize breast cancer therapy in real time, according to François-Clément Bidard, MD, PhD, of the Institut Curie, Paris, the study's author.

This phase 3 clinical trial, run in more than 80 French cancer centers, has enrolled 1,000 patients with estrogen receptor-positive, HER2-negative metastatic breast cancer who were treated with endocrine therapy. Using ddPCR based liquid biopsy tests -- done both before and during treatment -- the researchers are tracking the emergence of ESR1 mutations linked to endocrine therapy resistance. While the study is still ongoing, preliminary results indicate that ddPCR technology can rapidly detect the presence of ESR1 mutations.

"Droplet Digital PCR is the only cost-effective solution that enables us to track the onset in real time of ESR1 mutations in thousands of serial ctDNA samples," said Bidard.

If this study determines that switching patients with ESR1 mutations to a new treatment is more effective, ddPCR could potentially be applied in the clinical setting to continually monitor patients and help physicians know when to make that switch.

This ongoing study will be presented on Monday, April 1, 1:35-2 PM during Session SY31.

Bio-Rad's new scATAC-Seq solution and FDA-cleared QXDx BCR-ABL %IS Kit will be on display at Bio-Rad's booth (#2627). In addition, Bio-Rad will showcase its new ddPCR Multiplexing Supermix for detection of multiple targets. To learn more about Bio Rad's ddPCR technology, visit the booth or bio-rad.com/digitalPCR.

Neuroscientists at The University of Queensland have developed a new animal model of schizophrenia that will enable researchers around the world to better understand the disease and develop new treatments.

Schizophrenia, which affects around 7 people in 1000, is a poorly understood group of mental disorders that disrupt cognition and behaviour. Common hallmarks include delusions, hallucinations, and difficulty perceiving reality.

The precise neurological cause of schizophrenia is unknown and the development of better treatments are urgently needed. This research will provide a model to begin to address some of the underlying fundamental mechanisms involved.

What scientists do know is that schizophrenia is associated with a pronounced change in the way the brain uses dopamine, the neurotransmitter often referred to as the brain's 'reward molecule'.

"In schizophrenia patients, dopamine signalling significantly increases in a brain region called the striatum," explained Professor Darryl Eyles at UQ's Queensland Brain Institute.

"It is thought that some of the symptoms relate to an elevated production and release of dopamine," he said.

"New research also shows that these changes are most pronounced in the dorsal or upper portion of the striatum, not the ventral striatum where we've been focussed for many years."

However, it is still not clear why excessive dopamine release in that part of the striatum leads to the symptoms of schizophrenia, or what happens to other regions of the brain when dopamine is elevated in this area.

To address this, Prof Eyles, QBI PhD student Alice Petty, and their colleagues developed a new animal model of schizophrenia where dopamine is specifically elevated in the dorsal striatum.

The inspiration for the model came from recent studies on animal models of Parkinsons disease where dopamine is deficient, said Prof Eyles.

Petty delivered genetic constructs (that make dopamine) into the brain of rats. This was done using a virus to target the delivery only to dopamine neurons that project to the dorsal striatum.

These animals showed behavioural changes, such as increased locomotion under certain circumstances and impairments in monitoring sensory information which mimic some of the symptoms of schizophrenia.

"This is the first model to closely replicate the primary and most robust dopamine abnormality in schizophrenia by elevating levels of dopamine specifically in the dorsal striatum," Petty explained.

Eyles said that his research group and others can now use the model to test potential therapeutics that specifically target this abnormality.

"We plan to use this model to identify compounds that prevent unwanted dopamine release in the dorsal striatum. This could lead to treatments that could either diminish symptom severity or even prevent schizophrenia," he said.

"Importantly, we can also explore the basic changes that occur in the brain's circuitry that are altered when elevated levels of dopamine are produced in the dorsal striatum. This may help us to understand the basis of schizophrenia" he said.

"We can also look at how the disease might progress over time and how its onset first occurs."

The paper has now been published in the journal npj Schizophrenia.