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A new gene associated with disease severity in models of rheumatoid arthritis has been identified by researchers at the Icahn School of Medicine at Mount Sinai. The discovery could provide a new pathway for treatment and a way to measure the prognosis of patients diagnosed with the autoimmune condition.

Through a series of experiments--on synovial cells from the inner lining of joints in humans and animals, and in animal models of arthritis--Percio S. Gulko, MD, Chief of the Division of Rheumatology, Lillian and Henry M. Stratton Professor of Medicine (Rheumatology), and senior author on the paper, and his colleagues were able to show that the gene HIP1 is a driver in inflammatory arthritis severity. This is the first time that HIP1 has been implicated in arthritis severity and in cell invasiveness. The findings will be published online in Annals of the Rheumatic Diseases on Thursday, July 26.

Rheumatoid arthritis is a chronic disease affecting more than 1.3 million Americans. The disease can cause disability and deformation of joints and affects roughly 1 percent of the world's population. Drugs currently available to treat rheumatoid arthritis target the body's immune response but raise the risk of immunosuppression and susceptibility to infections such as herpes zoster and pneumonia.

"There have been major advances in the treatment of rheumatoid arthritis in the past 20 years, but disease remission still remains uncommon. Most drugs today target inflammation but often that is not enough to control disease," says Dr. Gulko. "At my laboratory, we have been looking for alternative strategies. In this research, we have focused on understanding the regulation of disease severity and joint damage. Our discovery led us to the synovial fibroblasts, cells inside the joint."

Through genetic strategies including linkage mapping and congenic breeding, in which specific chromosome fragments in arthritis-susceptible rodent strains are replaced with chromosome fragments from arthritis-resistant strains, Dr. Gulko and his co-researchers identified a chromosomal region that controls arthritis severity and joint damage.

This region contained 41 genes. They sequenced those genes and discovered a mutation in HIP1, a gene previously unrelated to arthritis or inflammation. The lab was then able to show that the different forms (alleles) of HIP1 affected the behavior of the synovial fibroblast, the cells that line the tissue in the inner surface of joints, by reducing or augmenting invasiveness of the cells. Synovial fibroblast enables local repair and production of the fluid that lubricates joints and nourishes the joint cartilage. In people with rheumatoid arthritis, the synovial fibroblasts increase in numbers (hyperplasia) and become invasive, and the synovial tissue becomes infiltrated with immune cells, causing joint swelling and pain. This invasive behavior is known to correlate with joint damage in patients with rheumatoid arthritis.

With this crucial information, the researchers moved on to the next experiment in synovial fibroblasts derived from patients with rheumatoid arthritis. The researchers knocked down (removed) the HIP1 gene in these synovial fibroblasts. Removing HIP1 significantly reduced the ability of the rheumatoid arthritis synovial fibroblasts to respond to PDGF (platelet-derived growth factor), a potent inducer of synovial fibroblast invasiveness expressed in increased levels in the joints of patients with rheumatoid arthritis. Knockdown of HIP1 prevented the activation of the signaling molecule Rac1, which is key for synovial fibroblast invasiveness. Dr. Gulko and his colleagues also studied HIP1-deficient mice. These mice were protected, and developed a milder form of the arthritis.

Previous research had found that increased HIP1 expression in certain cancers and correlated with worse prognosis in prostate cancer patients. Therefore, Dr. Gulko's findings also have potential relevance for cancer biology and the understanding of cancer cell invasion and metastasis.

"These new discoveries raise the future possibility of targeting HIP1 to treat rheumatoid arthritis, and also of quantifying HIP1 levels in the blood or synovial fluid cells to predict disease outcome," said Dr. Gulko.

Dr. Gulko's research provides a framework for a potential new target for therapy and, perhaps, a new predictor of a patient's prognosis. He and his colleagues plan in the future to investigate the feasibility of a drug that would target the HIP1 gene. "We are aiming for a novel way of treating the disease. One that targets the synovial fibroblast, while sparing the immune system outside the joint," he says.

Professor Arne Skerra of the Technical University of Munich (TUM) has succeeded for the first time in using gaseous CO2 as a basic material for the production of a chemical mass product in a biotechnical reaction. The product is methionine, which is used as an essential amino acid, particularly in animal feed, on a large scale. This newly developed enzymatic process could replace its current petrochemical production. The results have now been published in the journal Nature Catalysis.

The industrial production of methionine from petrochemical source materials is currently done via a six-step chemical process that requires highly toxic hydrogen cyanide, among other substrates. In 2013, Evonik Industries, one of the world's largest manufacturers of methionine, invited university researchers to propose new processes for making the substance safer to produce. Methional, which occurs in nature as a degradation product of methionine, is formed as a facile intermediate during the conventional process.

"Based on the idea that methionine in microorganisms is degraded by enzymes to methional with the release of CO2, we tried to reverse this process," explains Professor Arne Skerra from the Department of Biological Chemistry at TUM, "because every chemical reaction is in principle reversible, while often only with the extensive use of energy and pressure." Skerra participated in the call for proposals with this idea, and Evonik awarded the concept and supported the project.

Supported by postdoctoral researcher Lukas Eisoldt, Skerra began to determine the parameters for the manufacturing process and for producing the necessary biocatalysts (enzymes). The scientists conducted initial experiments and determined the CO2 pressure which would be needed to produce methionine from methional in a biocatalytic process. Surprisingly, an unexpectedly high yield resulted even at a relatively low pressure - approximately corresponding to the one in a car tire of approximately two bars. Based upon the achievements after just one year, Evonik extended the funding, and now the team, reinforced by the Ph.D. student Julia Martin, investigated the biochemical background of the reaction and optimized the enzymes involved using protein engineering.

More efficient than photosynthesis

After several years of work, not only was it possible to improve the reaction on a laboratory scale to a yield of 40 percent, but also to elucidate the theoretical background of the biochemical processes. "Compared to the complex photosynthesis, in which nature also biocatalytically incorporates CO2 into biomolecules as a building block, our process is highly elegant and simple," reports Arne Skerra. "Photosynthesis uses 14 enzymes and has a yield of only 20 percent, while our method requires just two enzymes."

In the future, the basic principle of this novel biocatalytic reaction can serve as a model for the industrial production of other valuable amino acids or precursors for pharmaceuticals. Meanwhile, Professor Skerra's team will refine the process, which has been patented, using protein engineering so that it will become suitable for large-scale application.

This could be the first time that there is a biotechnological manufacturing process using gaseous CO2 as an immediate chemical precursor. Up to now, attempts to recycle the greenhouse gas, which is a major contributor to climate change, have failed due to the extremely high energy required to do so.

It is more likely that you have seen a habu snake in a bottle of local rice liquor Awamori, in Okinawa, than that you've spotted one slithering by the wayside. Even so, habus are very common in the Ryukyu islands of which Okinawa is a part. Okinawa is home to three species of habu; the Okinawan habu (Protobothrops flavoviridis), endemic to the Ryukyu islands, is highly venomous.

A collaborative team of scientists from many research institutes and universities across Japan have now mapped the entire genome of the Okinawan habu including the genes involved in venom production. Professor Nori Satoh and his team of researchers from Okinawa Institute of Science and Technology Graduate University (OIST), were a part of the study, which was published in Scientific Reports. Snake venom has attracted the attention of many scientists worldwide as it has tremendous potential in the development of new drugs. The findings from this study might help advance efforts to identify novel therapies for treating ailments such as cancer, cardiovascular diseases and many others.

For the study, the researchers caught Okinawan habus from the wild using a long metal pole with a hook at one end and collected venom, blood and tissues samples from them. Then, using the cutting-edge DNA sequencing facilities at OIST, the researchers identified nearly 60 genes from 18 different gene families that help this critter make its venom.

Nearly 50 people - most often farm workers tending crops in fields and orchards - are reportedly bitten by habus every year in Okinawa alone. The venom of the Okinawan habu is hemotoxic, destroying the blood cells and tissues. Though antidotes are now available, bites can still cause severe pain and permanent tissue damage in humans. The scientists hope the results of this study will help develop more effective antidotes and treatments for habu bites. "The findings of this study are very important, especially to the people of Okinawa and the surrounding islands where the Okinawan habu is found", says Prof. Satoh.

Snake venom is a cocktail of complex proteins. "Though the Okinawan habu is not as venomous as cobras or taipans, it can produce a large amount of venom - up to 1 ml," says Prof. Hiroki Shibata, a collaborator from the University of Kyushu. Its long, sharp fangs help discharge the venom deep inside the prey, he explains.

The genome of any organism is a treasure trove of information. Mapping venom genes of the habu not only allows scientists to explore its potential in drug development, but also gives scientists the tools to study how venom toxins have evolved, their composition and the mechanism by which they do their damage.

The researchers explored this venom's evolutionary history by constructing a phylogenetic tree of venom genes including those that they identified in the habu. A phylogenetic tree helps illustrate the relationship between two or more organism groups by identifying the similarities and dissimilarities between them. The distance between the groups in a tree translates to different degrees of relatedness between them. The groups that are closely placed are more related to one another than those placed further away.

Venomous snakes across the world belong to one of the two families; Viperidae or Elapidae. The members of the family Viperidae, including the habu, have venom that is toxic to blood (hemotoxic); whereas the members of the family Elapidae, such as cobras, have venom that is toxic to the nervous system (neurotoxic). In this study, the researchers found many common components among venom genes of both families, thereby tracing back the origin of the present-day venom toxins to a common ancestor that existed millions of years ago. "The venom gene copies originated a long time ago, possibly at the early stage of vertebrate evolution" explains Prof. Shibata. The scientists believe that combined information gathered from venom research so far, will help unravel the enigma behind the process of venom production in snakes.

Alexandria, Va., USA - At the 96th General Session of the International Association for Dental Research (IADR), held in conjunction with the IADR Pan European Regional (PER) Congress, Paula Moynihan, Newcastle University, England, gave an oral presentation titled "Relationship Between Amount and Frequency of Sugars Intake by Children." The IADR/PER General Session & Exhibition is in London, England at the ExCeL London Convention Center from July 25-28, 2018.

Reducing both the amount and frequency of sugar intake is a significant topic in dentistry. Data from the 1980s indicated a strong correlation between amount and frequency of sugars intake, meaning reducing frequency would result in a reduction in amount. However, since then dietary lifestyle has changed considerably. Moynihan and co-authors sought to determine if an association between amount and frequency of sugars intake still exists and if reduction in the amount of sugars intake is associated with a reduction in intake frequency.

Existing dietary data as part of Public Health England's Sugar Smart Campaign was used to assess the amount of total sugars and free sugars intake and the frequency of consumption. Correlations between amount and frequency were determined. Linear regression was use to determine if a change in frequency of sugars was a predictor of change in the amount of sugar intake.

Moynihan and co-authors found that a strong relationship existed between the amount and frequency of sugars intake in modern diets. Reducing frequency of sugars consumption is likely to reduce amount consumed.

This research was presented as part of the Keynote Address; Different Impacts on Masticatory Function oral session that took place on Wednesday, July 25 from 1:30 p.m. - 3 p.m. at the ExCeL London Convention Center in London, England.

The disparity between the number of sexual partners reported by men and women can largely be explained by a tendency among men to report extreme numbers of partners, and to estimate rather than count their lifetime total, a new study in The Journal of Sex Research finds.

Together with gender differences in attitudes towards casual sex, this explains roughly two-thirds of the notorious 'gender gap' found in many sex surveys.

Dr Kirstin Mitchell of the University of Glasgow and colleagues analyzed the responses of over 15,000 men and women in the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Their study sought to better understand why men always report more opposite-sex partners on average than women, even though the average number reported by men and women should be about the same. In the Natsal-3 survey men reported an average of 14 lifetime partners while women reported only 7 (participant age range, 16-74).

Firstly, individuals who reported very high numbers of partners skewed the average, and this effect was stronger for men than women. Men and women at the top end (99th percentile) reported 110 and 50 or more partners respectively. Excluding these men and women reduced the overall average, closing the gender gap.

The gap reduced further when 'accounting strategy' was taken into consideration. Men were more likely than women to estimate rather than count their lifetime partners. For example, among those reporting 5-9 partners, 24% of men estimated compared with 15% of women.

Sexual attitudes also had an impact on reporting. Women were generally more conservative in their sexual attitudes than men. They were less likely than men to view one-night stands as 'not wrong at all' (9% versus 18%) and they were more likely to view a 'married person having sexual relations with someone other than his or her partner' as 'always wrong' (65% versus 57%). Adjusting for these attitudes narrowed the gap even further.

The researchers investigated a number of other explanations. They found that excluding paid-for partners made only a small difference to the gender gap, but gender differences in reported non-UK resident sexual partners had a modest impact over a 5-year period and could also be a potential explanation over the lifetime.

Dr Mitchell said: "Accurate reporting of sexual partners is crucial for many reasons, including assessing individual risk of sexually transmitted infections (STIs) and estimating the rate of STI/HIV transmission.

"Most existing studies of reporting bias are limited to students or high-risk populations, or are conducted as 'laboratory' settings, so they don't show how members of the public respond in a 'real-life' survey. To our knowledge, our study is the first attempt to look at all the key types of explanation for the gender discrepancy within the same large and representative sample."

University of Manchester and Salford Royal NHS Trust scientists have developed a lamp which could treat chronic ulcers with light.

The Arthritis Research UK funded trial led by Dr Michael Hughes tested the therapy - which combines infrared, red and ultraviolet light - on finger ulcers caused by a condition called systemic sclerosis, where the immune system attacks the body's fingers and toes.

Dr Hughes said the results were so emphatic, the device is a potential treatment for other ulcers, including diabetic and venous ulcers, a huge problem for tens of thousands of patients

People with diabetes are at risk of ulcers or open wounds that don't heal because of poor circulation, a complication of the condition.

Venous ulcers occur when blood doesn't flow from the lower legs back to the heart, causing a build-up of pressure in the veins.

The lamp built by the team has 32 different bulbs which emit infrared, red or ultraviolet light. Eight patients with 14 ulcers between them had the treatment.

In the study, published in the Journal of Dermatological Treatment today, the patients were treated using the lamp for 15-minute sessions, twice a week for three weeks.

After treatment, there was an average 83 per cent improvement in the ulcers, with no side-effects.

Scientists believe ultra-violet light, which cannot be seen by the naked eye, kill the bacteria and reduce the inflammation that prevents healing.

Red light is believed to boost blood circulation, increasing the supply of oxygen and nutrients needed for wound healing.

It is also thought to stimulate the production of the protein collagen in the skin, which provides the natural scaffolding to help new tissue grow.

And infrared light, used in TV remote controls, is associated with increasing blood flow and oxygen.

Patients having light therapy for ulcers, using lasers, are currently treated in hospital over five days and are forced to take medication which lower their blood pressure.

However, the new therapy can be administered at home and, says Dr Hughes, with SIM card technology can even be used to monitors patients' progress remotely.

He said: "We believe this technology is a game changer; the implications are huge.

"Ulcers cause much distress to patients - and current treatments are costly to the NHS and problematic for patients who can only receive them in hospital.

"But this technology is cheap and practical- it's really a no brainer as it can be administered at home.

"There are future possibilities as well: we think this device could be easily adapted to monitor ulcers remotely using cameras. They could also be programmed to recognise different parts of the body so that the treatment is given accurately.

"In the next 6 to 12 months we shall be refining the machine and within 12 months we hope to trialling it on diabetic ulcers."

New research gives insights into how the design of clinical trials can improve to address the "critically low" research pipeline and improve the chances of finding effective dementia therapies.

Against a backdrop of a number of high-profile clinical trial failures, research by the University of Exeter, presented in posters at the Alzheimer's Association International Conference (AAIC) 2018, highlights the importance of conducting more targeted trials. It gives insights into how to obtain better evidence that potential treatments may be effective*, and how to recruit specific groups of people to trials**.

Research presented at the conference*** highlights that there are currently 142 active clinical trials in Alzheimer's disease worldwide. Of these, only 42 are on disease-modifying therapies, only 29 of which were in phase 2 or 3 in drugs, small molecules or biological therapies - meaning they have any meaningful chance of translating to disease-modifying treatment for Alzheimer's disease. The research found this figure to be 40-fold lower than the number of cancer trials at this phase of progression.

Clive Ballard, Professor of Age-Related Diseases at the University of Exeter Medical School, said: "When we drilled down into the number of active clinical trials in dementia we revealed that the number that could make a meaningful difference to treating disease is now critically low. With no new licensed treatments in the last 20 years, addressing this shortfall is an urgent priority. . Our research outlines the new approach needed to enable us to do better by the 40 million people worldwide who have dementia, and for an economy which is projected to spend a trillion dollars on treating this disease by the end of 2018."

The research also revealed the targets that clinical trials are focussing on, highlighting where the scientific community thinks the best hope of treatment currently lies. Of the 29 identified by the team, ten are looking at treatment or approaches to amyloid and four at tau - both proteins that can build up in the brain. Three focus on neurotransmitters while three more are on repositioning other existing drugs. One is a regenerative treatment and one is targeting neuroinflammation.

Further research by the team highlights how future research can be targeted and conducted more efficiently. Conducting trials in groups such as those at high risk of developing dementia means fewer participants are needed to obtain an equal statistical power and reliability of results.

Increasingly, research is focussing on the early stages of dementia and dementia prevention, however the costs involved in recruitment are high, as large numbers are needed because of the varying pathways involved in dementia.

The Exeter-led study looked at data from the participants who were given placebos in three randomised clinical trials, of 939 people. They analysed biomarkers and risk factors such as genetics, the presence of amyloid plaque in the brain and a family history of Alzheimer's disease. They found that considering these factors significantly increases the power per patient screened to detect the potential for treatment to effect brain function.

In a study sponsored by the Wellcome Trust and led by King's College London, working with Exeter, researchers analysed a library of compounds 1,300 in the Broad Institute connectivity Map, to select which would be the best candidates to take forward to clinical trials for Alzheimer's disease. They used mouse models to look at which of these compounds changed MRNA expression in cancer cells, making them candidates as disease-modifying treatments in dementia.

Of these, they then 83 to test in cells, and selected the most promising six of those to take forward in mice. They analysed aspects including whether they protect cells from exposure to amyloid or tau proteins, implicated in dementia, or whether they protect synapse and nerve activity.

The researchers conclude that this approach can increase the potential to screen existing compounds that have potential to be effective treatments for Alzheimer's disease, and refine those that should be taken forward to clinical trial.

TORONTO, July 25, 2018 - Engaging patients in the redesign of health care services can lead to reduced hospital admissions and more efficient and effective health care, a study led by a St. Michael's Hospital researcher suggests.

In their study, Engaging Patients to Improve Quality of Care: A Systematic Review, published today in Implementation Science, lead authors Dr. Yvonne Bombard and Dr. G. Ross Baker concluded that active engagement of patients can inform education, tools, planning and policy, and enhance health care service delivery and governance.

The review, which examined 48 studies from across the globe that addressed patient participation in the design and delivery of health care services, further concluded that higher levels of patient engagement were associated with efforts to develop higher level system outcomes for health care, including improved quality of care, governance and service delivery.

"We looked at all the international literature across all care settings, and we found that the more patients were engaged as partners and co-designers, the higher the level of outcomes," said Dr. Bombard, a scientist at the Li Ka Shing Knowledge Institute at St. Michael's Hospital. "There are different levels of engagement. If patients were just consulted, often what we saw in terms of outputs were products like patient information kits. Yet active involvement of patients as partners in design was linked to more substantial outcomes like designing new delivery systems, adding support systems like a mental health advocate, all the way up to creating new governance documents and policies at the top echelons of the hospital."

Dr. Baker, professor and program lead, quality improvement and patient safety, at the University of Toronto's Institute of Health Policy, Management and Evaluation, pointed out that higher levels of engagement require additional investments in training and support that would only be appropriate for larger projects.

"If you really want to focus on redesigning care, you have to bring in patients in a much more active way," he said. "The key message is that there are successful examples of people who have engaged patients to do broad scale redesign, and we should learn from the strategies they've used. And there's more research needed to detail what patient engagement strategies are suitable for what kinds of projects."

Some of those strategies include providing appropriate training for higher-level involvement--not just for patients but for providers as well -- and being flexible and respectful of patients' time and experiences.

"Patients have a unique experience that gives them a different view on what happens in hospitals and other health services, and their insights can be helpful in identifying duplication, waste, failure to coordinate and other issues" said Dr. Baker. "Providers see the care that they're directly engaged in, but the patient sees all the care."

"Hospitals often do this on some level, but sometimes it's done in an ad hoc fashion," Dr. Bombard said. "I think that does a disservice to the science of patient engagement, and over time it might start to create distrust among patients. We hope this work advances the science and methodology of patient engagement so that we're sure we're doing it effectively, for the intended purposes ."

Maunakea, Hawaii - A team of astronomers has discovered a new way to unlock the mysteries of how the first galaxies formed and evolved.

In a study published today in Astrophysical Journal Letters, lead author Dawn Erb of the University of Wisconsin-Milwaukee and her team - for the very first time - used new capabilities at W. M. Keck Observatory on Maunakea, Hawaii to examine Q2343-BX418, a small, young galaxy located about 10 billion light years away from Earth.

This distant galaxy is an analog for younger galaxies that are too faint to study in detail, making it an ideal candidate for learning more about what galaxies looked like shortly after the birth of the universe.

BX418 is also attracting astronomers' attention because its gas halo is giving off a special type of light.

"In the last several years, we've learned that the gaseous halos surrounding galaxies glow with a particular ultraviolet wavelength called Lyman alpha emission. There are a lot of different theories about what produces this Lyman alpha emission in the halos of galaxies, but at least some of it is probably due to light that is originally produced by star formation in the galaxy being absorbed and re-emitted by gas in the halo," said Erb.

Erb's team, which includes Charles Steidel and Yuguang Chen of Caltech, used one of the observatory's newest instruments, the Keck Cosmic Web Imager (KCWI), to perform a detailed spectral analysis of BX418's gas halo; its properties could offer clues about the stars forming within the galaxy.

"Most of the ordinary matter in the universe isn't in the form of a star or a planet, but gas. And most of that gas exists not in galaxies, but around and between them," said Erb.

The halo is where gas enters and exits the system. The gas surrounding galaxies can fuel them; gas from within a galaxy can also escape into the halo. This inflow and outflow of gas influences the fate of stars.

"The inflow of new gas accreting into a galaxy provides fuel for new star formation, while outflows of gas limit a galaxy's ability to form stars by removing gas," says Erb.

"So, understanding the complex interactions happening in this gaseous halo is key to finding out how galaxies form stars and evolve."

This study is part of a large ongoing survey that Steidel has been leading for many years. Previously, Steidel's team studied BX418 using other instruments at Keck Observatory.

This most recent study using KCWI adds detail and clarity to the image of the galaxy and its gas halo that was not possible before; the instrument is specifically engineered to study wispy currents of faint gas that connect galaxies, known as the cosmic web.

"Our study was really enabled by the design and sensitivity of this new instrument. It's not just an ordinary spectrograph--it's an integral field spectrograph, which means that it's a sort of combination camera and spectrograph, where you get a spectrum of every pixel in the image," said Erb.

The power of KCWI, combined with the Keck telescopes' location on Maunakea where viewing conditions are among the most pristine on Earth, provides some of the most detailed glimpses of the cosmos.

Erb's team used KCWI to take spectra of the Lyman alpha emission of BX418's halo. This allowed them to trace the gas, plot its velocity and spatial extent, then create a 3-D map showing the structure of the gas and its behavior.

The team's data suggests that the galaxy is surrounded by a roughly spherical outflow of gas and that there are significant variations in the density and velocity range of this gas.

Erb says this analysis is the first of its kind. Because it has only been tested on one galaxy, other galaxies need to be studied to see if these results are typical.

Now that the team has discovered a new way to learn about the properties of the gaseous halo, the hope is that further analysis of the data they collected and computer simulations modeling the processes will yield additional insights into the characteristics of the first galaxies in our universe.

"As we work to complete more detailed modeling, we will be able to test how the properties of Lyman alpha emission in the gas halo are related to the properties of the galaxies themselves, which will then tell us something about how the star formation in the galaxy influences the gas in the halo," Erb said.

Researchers from King's College London have assessed just how much sun protection people actually receive, based on typical use. It is well known that people don't receive the full ultraviolet radiation blocking benefit of sunscreen, because they are applying it more thinly than manufacturers recommend. The findings are published in journal Acta Dermato-Venereology.

In the first experiment of its kind, the King's team assessed the DNA damage in the skin after lowering sunscreen application thickness below 2mg/cm2 - the amount manufacturers use to achieve their SPF rating.

Results showed that sunscreen with a sun protection factor (SPF) of 50, applied in a typical way, would at best provide 40% of the expected protection. The findings have prompted the King's team to suggest that consumers use a much higher SPF sunscreen than they think necessary, to ensure they're protected from sun damage.

As part of the research scientists divided a cohort of 16 fair-skinned volunteers into two groups of eight - (three women and five men in each). One group received a single UVR exposure, to simulate sunlight, to areas treated with high SPF sunscreen of varying thickness, ranging from 0.75mg, through 1.3mg up to 2mg/cm2.

The other group received exposures on five consecutive days - to mimic continuous holiday exposure. The amount of UVR exposure was varied during the course of the experiment, in order to replicate the conditions in holiday destinations, such as Tenerife, Florida and Brazil.

Biopsies of the UVR exposed areas of skin showed that, for the group that were repeatedly exposed to UVR, considerable DNA damage was found on the areas that received no sun protection, even though the UVR dose was very low.

Damage was reduced when sunscreen was applied at a thickness of 0.75mg/cm2 and considerably reduced when 2mg/cm2 of sunscreen was applied, even with much higher UVR doses.

Five days of exposure to high dose UVR with the sunscreen at 2mg/cm2 showed significantly less damage than just one day's low UVR dose exposure without sunscreen across all samples.

Report author, Professor Antony Young from King's College London said: 'There is no dispute that sunscreen provides important protection against the cancer causing impact of the sun's ultra violet rays. However, what this research shows is that the way sunscreen is applied plays an important role in determining how effective it is.

'Given that most people don't use sunscreens as tested as tested by manufacturers, it's better for people to use a much higher SPF than they think is necessary.

Nina Goad of the British Association of Dermatologists said: 'This research demonstrates why it's so important to choose an SPF of 30 or more. In theory, an SPF of 15 should be sufficient, but we know that in real-world situations, we need the additional protection offered by a higher SPF.

'It also shows why we shouldn't rely on sunscreen alone for sun protection, but we should also use clothing and shade. An extra consideration is that when we apply sunscreen, we are prone to missing patches of skin, as well as applying it too thinly.'

A new special issue of SLAS Discovery reflects examples of the recent groundswell of creative new applications for high-throughput flow cytometry (HTFC) in drug discovery.

Led by guest editors Mei Ding, Ph.D. (AstraZeneca) and Bruce S. Edwards, Ph.D. (University of New Mexico), this special issue presents a range of research papers, application notes and technical notes that reflect recent advances in HTFC methods design, provide new expert insight and perspectives, and highlight areas for improvement to broaden the range of HTFC applications in drug discovery.

Examples include descriptions of different software and data analysis workflows; the relative merits of different platforms for assessing biological responses of interest; novel HTFC applications for the development of biologic drugs and novel antibodies; target-agnostic or mechanism-informed phenotypic drug discovery; use of HTFC for single cell analysis; engineering autologous patient T cells to express chimeric antigen receptors (CAR-T) for use in adoptive cellular therapy of malignancies; and more.

Flow cytometry has proven to be a powerful technology, enabling multi-parametric analysis of single cells or particles, and widely used in a broad range of clinical and basic research and applications, including quantification of cell surface and intracellular proteins, DNA analysis, cell proliferation, cell viability, cellular granularity, and cell size. HTFC was made possible by the introduction of novel sample handling and analysis technologies.

LA JOLLA--(July 24, 2018) Can you tell the smell of a rose from the scent of a lilac? If so, you have your brain's piriform cortex to thank. Compared to many parts of the brain, the piriform cortex--which lets animals and humans process information about smells--looks like a messy jumble of connections between cells called neurons. Now, Salk Institute researchers have illuminated how the randomness of the piriform cortex is actually critical to how the brain distinguishes between similar odors.

"The standard paradigm is that information in the brain is encoded by which cells are active, but that's not true for the olfactory system," says Charles Stevens, Distinguished Professor Emeritus in Salk's Molecular Neurobiology Laboratory and coauthor of the new work. "In the olfactory system, it turns out it's not a matter of which cells are active, but how many cells are active and how active they are."

Aside from better understanding how smells are processed, the new research, published in the Journal of Comparative Neurology on July 17, 2018, could also lead to greater insight into how some parts of the brain organize information.

When odorant molecules--the signature of any given smell--bind to the receptors in a person's nose, the signal is transmitted to the olfactory bulb, and from there to the piriform cortex. In other sensory systems--like the visual system--information maintains a strict order as it moves through the brain. Particular parts of the eye, for instance, always transmit information to specific parts of the visual cortex. But researchers have long known that this order is missing in the piriform cortex.

"We haven't been able to discern any order in the piriform cortex connections in any species," says coauthor Shyam Srinivasan, an assistant project scientist at the University of California San Diego's Kavli Institute for Brain and Mind. "Any given odor lights up about 10 percent of neurons that seem to be scattered all over the piriform cortex."

To start working out the details of how the piriform cortex encodes odor information--and whether its connections are truly random--Stevens and Srinivasan analyzed the piriform cortices of nine mice using a variety of staining and microscopy techniques that let them visualize different cell types in the brain region. Their first goal: to quantify the number and density of cells in the piriform cortex.

"This was really like a survey," explains Srinivasan. "We counted the cells in different representative areas and averaged them across the whole region."

The mouse piriform cortex, they concluded, has around half a million neurons in it, divided equally between the larger, less dense posterior piriform and the smaller, more dense anterior piriform.

Using this initial information on density and neuron number, as well as knowledge from previous studies on the number of neurons in the olfactory bulb and how many neuronal connections--or synapses--connect the olfactory bulb to the piriform cortex, the pair of researchers was able to draw a surprising finding: each neuron in the olfactory bulb is connected to nearly every single neuron in the piriform cortex.

"Every cell in the piriform is getting information from essentially every odor receptor there is," says Stevens. "There's not one 'coffee smell' neuron but a whole bunch of coffee cell neurons all over the place." Rather than a single receptor detecting one odor and lighting up one cluster of telltale neurons, he explains, each odor has a fingerprint that's based more on the strength of the connections--while the smell of coffee may activate nearly the same neurons in the piriform cortex as the smell of chocolate, they'll activate each neuron to a different degree.

"One advantage to this system is that it can encode very complex information," says Srinivasan. "It also makes it very robust to noise." If one neuron sends a "noisy" signal--stronger or weaker activation than it should--the noise gets cancelled out by the many other neurons sending simultaneous, more accurate signals.

The researchers would like to repeat the work in other animals to see where similarities and differences lie. They also are interested in looking into other areas of the brain that have long been assumed to be dominated by seemingly random connections to see if they're organized in the same way.

Stevens and Srinivasan, who also had a paper come out in the Journal of Neuroscience on July 13 about using the fruit fly olfactory learning circuit to improve the current crop of deep learning algorithms, were funded by the Kavli Institute for Brain and Mind at UC San Diego and the National Science Foundation.

Scientists have discovered that some treatments for cancer and sickle cell disease can destroy the germ cells that go on to develop into sperm in the testes of young boys. In some pre-pubescent boys, the treatment for sickle cell disease results in complete destruction of all their germ cells, which are called spermatogonia.

The study, which is published today (Wednesday) in Human Reproduction [1], one of the world's leading reproductive medicine journals, is the first to describe the effects of these treatments on spermatogonial quantity, although boys who have undergone chemotherapy or radiotherapy are known to be at risk of reduced fertility in adulthood.

As a result of their findings, the researchers say that if doctors plan to remove and freeze testicular tissue for fertility preservation, this should be performed before boys undergo a type of chemotherapy that uses high doses of drugs called 'alkylating agents'. This would give the boys some hope of restoring their fertility when they become adults. Before puberty, boys are usually unable to produce sperm samples that can be frozen and preserved for a time when they might want to start a family. Transplantation of testicular tissue back into the patients after treatment is a possible way of restoring fertility, but, at present, ways to generate sperm from preserved immature testicular tissue are experimental and there have been no pregnancies so far. It may also depend on having sufficient quantities of successfully preserved healthy spermatogonia.

Led by Dr Jan-Bernd Stukenborg, associate professor at the Karolinska Institutet and University Hospital (Stockholm, Sweden), a group of international researchers analysed testicular tissue taken for fertility preservation between 2014 and 2017 from 32 boys with an average age of six, living in Sweden, Finland and Iceland, who were facing treatments that carried a high risk of infertility: testicular irradiation, chemotherapy or radiotherapy as a preparation for a bone marrow transplant because they had cancer or blood disorders such as sickle cell disease, thalassaemia major or Fanconi anaemia. Sickle cell disease is the major reason for bone marrow transplantation in children who do not have cancer. Twenty boys had the tissue taken after initial chemotherapy and 12 had it taken before starting any treatment [2]. In addition, they looked at 14 healthy testicular tissue samples stored in the biobank at the Karolinska hospital.

They counted the number of germ cells found in a cross-section of little tubes in the testes where spermatogonia are created, called seminiferous tubules. "We could compare the number of spermatogonia with those found in the healthy boys as a way to estimate the effect of medical treatment or the disease itself on the future fertility of a patient," explained Dr Stukenborg.

"We found that the numbers of germ cells present in the cross-sections of the seminiferous tubules were significantly depleted and close to zero in patients treated with alkylating agents. The germ cell pool in five boys with sickle cell disease were totally depleted and very low in another; all six had received hydroxyurea. This was not seen in patients who had not started treatment, or were treated with non-alkylating agents, or in the biobank tissues." [3]

Alkylating agents are used in some chemotherapies, killing cancer cells by damaging their DNA. Hydroxyurea is a chemotherapy agent that is often used to treat the effects of blood disorders such as sickle cell disease, where it improves the function of red blood cells. It reduces the symptoms of the sickle cell disease but is not a cure. Bone marrow transplants offer the best chance of a cure or long-term remission. However, before a transplant, the patient's own bone marrow has to be destroyed and the immune system suppressed by radiation or chemotherapy so that the body does not reject the transplant from another person.

Co-author, Dr Cecilia Petersen, a senior consultant in paediatric oncology at the Karolinska Institutet, said: "Our findings of a dramatic decrease in germ cell numbers in boys treated with alkylating agents and in sickle cell disease patients treated with hydroxyurea, suggest that storing frozen testicular tissue from these boys should be performed before these treatments are initiated. This needs to be communicated to physicians, as well as patients and their parents or carers.

"However, until sperm that are able to fertilise eggs are produced from stored testicular tissue, we cannot confirm that germ cell quantity might determine the success of transplantation of the tissue in adulthood. Further research on this is needed to establish a realistic fertility preservation technique."

The authors point out that for some boys the disease itself may have already affected the number of spermatogonia before any treatment has even begun, and so for them preserving testicular tissue may not be a viable option. Co-author, Professor Kirsi Jahnukainen, a senior consultant in paediatric oncology at the Children's Hospital, University of Helsinki, Helsinki University Central Hospital (Helsinki, Finland), said: "Among patients who had not been treated previously with chemotherapy, there were several boys with a low number of germ cells for their age. This suggests that some non-malignant diseases that require bone marrow transplants may affect the fertility of young boys even before exposure to therapy that is toxic for the testes."

The researchers say that it is possible for germ cells to recover to normal levels after treatment that is highly toxic to the testes, but that high doses of alkylating agents and radiotherapy to the testicles, including total body irradiation, is strongly associated with permanent or long-term infertility.

Prof Jahnukainen added: "The first group of boys who received bone marrow transplants are now reaching their thirties. Recent data suggest they may have a high chance of their sperm production recovering, even if they received high dose alkylating therapies, so long as they had no testicular irradiation."

A limitation of the study was that the samples of normal tissue from the biobank had no detailed information regarding previous medical treatments and testicular volumes for these patients.

Dyslexia, a reading disorder, is characterized by a difficulty in "decoding" -- navigating between the visual form and sounds of a written language. But a subset of dyslexic people, dubbed "resilient dyslexics," exhibit remarkably high levels of reading comprehension despite difficulties decoding. What is the precise mechanism that allows certain individuals with dyslexia to overcome their low decoding abilities and ultimately extract meaning from text?

A new joint Tel Aviv University and University of California San Francisco study identifies the brain mechanism that accounts for the discrepancy between low decoding skills and high reading comprehension.

The research was led jointly by Dr. Smadar Patael of TAU's Department of Communication Disorders and Prof. Fumiko Hoeft, who is currently at the University of California San Francisco and starts as director of the University of Connecticut's Brain Imaging Research Center this fall. The research was recently published in PLOS One.

Measuring gray matter

The research points to a larger volume of gray matter in resilient readers in the part of the brain responsible for executive functions and working memory. This specific region, the dorsolateral prefrontal cortex (DLPFC) of the left hemisphere, is known as the "air traffic controller" or "conductor" of the brain. Gray matter is the darker tissue of the brain and spinal cord, consisting mainly of nerve cell bodies and branching dendrites.

Researchers examined 55 English-speaking children aged 10-16 with a wide range of reading abilities. Half of these children had been diagnosed with dyslexia. The researchers created a simple formula to calculate the difference between the reading abilities and decoding skills of the participants. The participants were scanned with an MRI. The researchers then compared the mapped images of the participants' brains with their reading skill results.

"We wanted to find whether the brain regions related to language or other regions were responsible," says Dr. Patael. "We found that the region in the left frontal part of the brain known as left DLPFC was directly related to this discrepancy. DLPFC has been shown to be important for executive functions and cognitive controls."

The chicken or the egg?

"We then sought to understand answer a 'chicken or egg' question related to dyslexia and the slight enlargement of this brain region," Dr. Patael continues. "Do resilient dyslexics have distinct brain structures that allow for better resiliency, or is their success in reading a result of compensation strategies that actually altered the density of neurons in a specific region of the brain?"

To answer this question, Dr. Patael, Prof. Hoeft and their colleagues scanned 43 kindergarteners using MRI technology, and then three years later tested the children's reading abilities. The researchers found that the density of neurons in the DLPFC predated mature reading ability and predicted the discrepancy, regardless of their initial reading abilities.

"This helps us to understand the brain and cognitive mechanisms these children utilize to enable them to do well despite their relative weakness in decoding. It may help us think about incorporating relatively new strategies into reading interventions," says Prof. Hoeft.

"Much of the curriculum of kindergarten reading readiness is focused on learning sounds of letter and phonological awareness," concludes Dr. Patael. "Our research findings suggest new approaches that emphasize executive functions and working memory. If your child is entering first grade, practicing the alphabet may not be enough. Consider activities that require working memory, such as baking cakes and playing song and strategy games. These activities stimulate children's working memory and may in time foster their ability to comprehend texts well."

The researchers are currently further exploring the neural mechanisms of compensation and resilience.