Earth

Nitroproston (11(S),15(S)-dihydroxy-9-keto-5Z,13E-prostadienoic acid 1?,3?-dinitroglycerol ester) is a novel prostaglandin-based compound with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Its pharmacological activity is provided by combined multi-target action on prostanoid EP4 receptors and soluble guanylylcyclase. Nitroproston is bearing a prostaglandin E2 (PGE2) moiety modified by an additional NO-donating fragment of glycerol-1,3-dinitrate (1,3-GDN) via ester bond and can be consider as nitrated derivative of glycerol ester of PGE2 ? the natural COX-2 metabolite of endogenous cannabinoid-like molecule 2-arachidonoyl glycerol. The presence of NO-donating fragment extremely changes pharmacological properties of PGE2. Nitroproston is more than 20-fold as active as prostaglandin E2 in the relaxation of respiratory muscles. Due to this enhanced myorelaxant activity Nitroproston is well tolerated by asthmatic subjects and is the first-in-class pharmaceutical candidate for therapy of asthma attacks utilized both prostanoid and NO receptors.

Despite the fact that Nitroproston has been extensively studied using various pharmacological models, its biological stability is still unknown. Thereby, the main aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its biodegradation products. The principal in vitro biodegradation products of Nitroproston were identified using liquid chromatography/ion trap - time-of-flight mass-spectrometry (LC-HRMS/MS). The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by target liquid chromatography/triple-stage quadrupole mass spectrometry (LC-MS/MS).

LC-HRMS/MS of spiked rat plasma samples clearly indicated the presence of two main metabolites of Nitroproston - 1,3-GDN and PGE2, the later can undergo dehydration to cyclopentenone prostaglandins. The applied LC-HRMS/MS screening method did not reveal the presence of biodegradation products of Nitroproston with one nitro-group or PGE2 glycerol ester. We assume that nitrate esters are more resistant to enzymatic hydrolysis in rat plasma than carboxyl ester moieties.

Target LC-MS/MS quantitative analysis was used to quantify the amount of Nitroproston and its major biodegradation products in rodent's plasma. The degradation was higher in rat plasma where only 5 % of parent Nitroproston was identified at the first moment of incubation. Similar pattern was observed for rabbit plasma where half-life (T1/2) of Nitroproston was about 2.0 minutes. Additionally, whole human blood and plasma samples were taken to perform stability and blood cell distribution study. Nitroproston biodegradation rate for human plasma was the slowest (T1/2 = 2.1 h) among tested species, but occurred more rapidly in whole blood (T1/2 = 14.8 min). Nitroproston was distributed between human RBCs and plasma with partition ratio of 0.82. These data suggest that metabolism of drug candidate in human whole blood was mainly associated with an enzymes located in RBC fraction. The observed interspecies variability highlights the need of suitable animal model selection for Nitroproston follow-up PK/PD studies. Our findings do not exclude that Nitroproston may be relatively stable in human after inhalation and may exert its therapeutic actions either as a whole drug molecule or as a prostaglandin E2 and nitric oxide prodrugs thanks to its active metabolites.

Nitroproston is being developed as a drug candidate for relief of bronchial asthma. The key principle of the action of Nitroproston is not only the effect on two targets having similar pharmacological activity with respect to bronchial smooth muscle, but also the synchronization of the pharmacological activity when the prostaglandin E2 is the driver of the donor part releasing the NO in the activity sites. Due to this, a powerful synergy of pharmacological activity is achieved and the dose of PGE2 drops sharply, which brings us back to the possibility of starting new and more successful attempts to use the of NO donating PGE2 derivatives for relief the bronchial asthma.

For more information about the research, please visit: http://www.eurekaselect.com/160373/article

March 25, 2018 - Boston - In the natural world, intelligence takes many forms. It could be a bat using echolocation to expertly navigate in the dark, or an octopus quickly adapting its behavior to survive in the deep ocean. Likewise, in the computer science world, multiple forms of artificial intelligence are emerging - different networks each trained to excel in a different task. And as will be presented today at the 25th annual meeting of the Cognitive Neuroscience Society (CNS), cognitive neuroscientists increasingly are using those emerging artificial networks to enhance their understanding of one of the most elusive intelligence systems, the human brain.

"The fundamental questions cognitive neuroscientists and computer scientists seek to answer are similar," says Aude Oliva of MIT. "They have a complex system made of components - for one, it's called neurons and for the other, it's called units - and we are doing experiments to try to determine what those components calculate."

In Oliva's work, which she is presenting at the CNS symposium, neuroscientists are learning much about the role of contextual clues in human image recognition. By using "artificial neurons" - essentially lines of code, software - with neural network models, they can parse out the various elements that go into recognizing a specific place or object.

"The brain is a deep and complex neural network," says Nikolaus Kriegeskorte of Columbia University, who is chairing the symposium. "Neural network models are brain-inspired models that are now state-of-the-art in many artificial intelligence applications, such as computer vision."

In one recent study of more than 10 million images, Oliva and colleagues taught an artificial network to recognize 350 different places, such as a kitchen, bedroom, park, living room, etc. They expected the network to learn objects such as a bed associated with a bedroom. What they didn't expect was that the network would learn to recognize people and animals, for example dogs at parks and cats in living rooms.

The machine intelligence programs learn very quickly when given lots of data, which is what enables them to parse contextual learning at such a fine level, Oliva says. While it is not possible to dissect human neurons at such a level, the computer model performing a similar task is entirely transparent. The artificial neural networks serve as "mini-brains that can be studied, changed, evaluated, compared against responses given by human neural networks, so the cognitive neuroscientists have some sort of sketch of how a real brain may function."

Indeed, Kriegeskorte says that these models have helped neuroscientists understand how people can recognize the objects around them in the blink of an eye. "This involves millions of signals emanating from the retina, that sweep through a sequence of layers of neurons, extracting semantic information, for example that we're looking at a street scene with several people and a dog," he says. "Current neural network models can perform this kind of task using only computations that biological neurons can perform. Moreover, these neural network models can predict to some extent how a neuron deep in the brain will respond to any image."

Using computer science to understand the human brain is a relatively new field that is expanding rapidly thanks to advancements in computing speed and power, along with neuroscience imaging tools. The artificial networks cannot yet replicate human visual abilities, Kriegeskorte says, but by modeling the human brain, they are furthering understanding of both cognition and artificial intelligence. "It's a uniquely exciting time to be working at the intersection of neuroscience, cognitive science, and AI," he says.

Indeed, Oliva says; "Human cognitive and computational neuroscience is a fast-growing area of research, and knowledge about how the human brain is able to see, hear, feel, think, remember, and predict is mandatory to develop better diagnostic tools, to repair the brain, and to make sure it develops well."

-

Oliva and Kriegeskorte are presenting in the symposium "Human and machine cognition: The deep learning challenge" at the CNS annual meeting in Boston. More than 1,500 scientists are attending the meeting from March 24-27, 2018.

CNS is committed to the development of mind and brain research aimed at investigating the psychological, computational, and neuroscientific bases of cognition. Since its founding in 1994, the Society has been dedicated to bringing its 2,000 members worldwide the latest research to facilitate public, professional, and scientific discourse.

New Orleans, LA - An international team of researchers led by Lucio Miele, MD, PhD, Professor and Chair of Genetics at LSU Health New Orleans School of Medicine, and Justin Stebbing, BM BCh MA, PhD, Professor of Cancer Medicine and Medical Oncology at Imperial College of Medicine in London, has found new genetic mutations that promote the survival of cancer cells. The research also provided a clearer understanding of how some cancer cells are able to resist treatment. The findings are published in PLOS ONE, available here.

"All cancers are caused by genetic damage, mutations to key genes that control the lives of cells," notes Dr. Miele, who also heads LSU Health New Orleans' Precision Medicine Program. "Mutant genes that cancers depend upon for survival are called 'driver' mutations."

The researchers tested genes in 44 cancers that no longer responded to therapy. These are not often tested in clinical practice. The tumor types included breast, lung, colorectal, sarcomas, neuroendocrine, gastric and ovarian, among others. They found that these advanced cancers had selected many new possible "driver" mutations never described before, in addition to drivers already known -- the cancers had evolved new driver mutations to become resistant.

No two cancers were genetically identical, even cancers of the same organs that looked the same under a microscope. In some cases, the researchers found evidence that an individual cancer had evolved two or even three drivers in the same gene, a sign that multiple cancer cell clones had evolved in the same tumor that had found different ways of mutating a particularly important gene. Many of these new genetic mutations are in functional pathways that can be targeted with existing drugs.

"These findings imply that genomic testing should be performed as early as possible to optimize therapy, before cancers evolve new mutations, and that recurrent cancers should be tested again, because their driver mutation may be different from those that existed at diagnosis," says Miele.

With this information, therapy could be tailored to the evolving genomic picture of each individual cancer -- the hallmark of precision medicine.

"We are working toward a day when we won't have to give a patient the devastating news that a cancer has come back and isn't responding to chemotherapy," Miele concludes.

Exposures of pregnant women and children to common thyroid-hormone-disrupting toxins may be linked to the increased incidence of brain development disorders, according to a review published in Endocrine Connections. The review describes how numerous, common chemicals can interfere with normal thyroid hormone actions, which are essential for normal brain development in foetuses and young children, and suggests a need for greater public health intervention.

Maternal thyroid hormones (TH) are essential for normal brain development of children and previous human studies have indicated that even moderate disruption to TH function in pregnant women may affect cognitive development and increase the risk of brain developmental disorders in their children. In modern times, an increase in chemical production has led to widespread environmental chemical contamination that can affect normal hormone function in those exposed, particularly in vulnerable populations, such as children and pregnant women. Many of these identified endocrine-disrupting chemicals (EDCs), which include pesticides and substances used in manufacturing a multitude of products, have been reported to interfere with thyroid hormone function, yet public health policy does not fully address the risks to vulnerable populations.

In this review, Professor Barbara Demeneix and colleagues at the Centre National de la Recherche Scientifique, Université Paris-Sorbonne, examine published evidence of the wide variety and high number of EDCs, from pesticides to chemicals used in the manufacture of drugs, cosmetics, furniture and plastics, that can all interfere with TH. The authors further highlight that complex mixtures of these thyroid-disrupting chemicals are present in all humans, including children and pregnant women.

Prof Barbara Demeneix comments, "We have reviewed the documented exposures of pregnant women and children to mixtures of thyroid-hormone-disrupting chemicals and propose that the data sets provide a plausible link to the recent increased incidence of neurodevelopmental conditions, including autism spectrum disorders and attention deficit hyperactivity disorders."

These findings indicate that exposures of pregnant women and children to thyroid-disrupting chemicals in the environment pose real risks for child development and health, and underline the need for a more targeted public health intervention strategy.

Prof Demeneix continues, "Many experts in the field, consider that the current testing guidelines for thyroid-disrupting chemicals are not sufficiently sensitive, do not take into account recent findings and do not adequately consider risks to vulnerable populations, such as pregnant women."

Sea ice in the Arctic grew to its annual maximum extent last week, and joined 2015, 2016 and 2017 as the four lowest maximum extents on record, according to scientists at the NASA-supported National Snow and Ice Data Center (NSIDC) and NASA.

On March 17, the Arctic sea ice cover peaked at 5.59 million square miles (14.48 million square kilometers), making it the second lowest maximum on record, at about 23,200 square miles (60,000 square kilometers) larger than the record low maximum reached on March 7, 2017.

More significantly from a scientific perspective, the last four years reached nearly equally low maximum extents and continued the decades-long trend of diminishing sea ice in the Arctic. This year's maximum extent was 448,000 square miles (1.16 million square kilometers) -- an area larger than Texas and California combined - below the 1981 to 2010 average maximum extent.

Every year, the sea ice cover blanketing the Arctic Ocean and surrounding seas thickens and expands during the fall and winter, reaching its maximum yearly extent sometime between late February and early April. The ice then thins and shrinks during the spring and summer until it reaches its annual minimum extent in September. Arctic sea ice has been declining both during the growing and melting seasons in recent decades.

The decline of the Arctic sea ice cover has myriad effects, from changes in climate and weather patterns to impacts on the plants and animals dependent on the ice, and to the indigenous human communities that rely on them. The disappearing ice is also altering shipping routes, increasing coastal erosion and affecting ocean circulation.

"The Arctic sea ice cover continues to be in a decreasing trend and this is connected to the ongoing warming of the Arctic," said Claire Parkinson, senior climate scientist at NASA's Goddard Space Flight Center in Greenbelt, Maryland. "It's a two-way street: the warming means less ice is going to form and more ice is going to melt, but also, because there's less ice, less of the sun's incident solar radiation is reflected off, and this contributes to the warming."

The Arctic has gone through repeated warm episodes this winter, with temperatures climbing more than 40 degrees above average in some regions. The North Pole even experienced temperatures above the freezing point for a few days in February.

In mid-March, cooler temperatures and winds pushed out the edge of the sea ice pack and caused a late surge in ice growth that brought the maximum extent closer in line with the past few years.

In February, a large area of open water appeared in the sea ice cover north of Greenland, within the multiyear ice pack -- the Arctic's oldest and thickest ice. Most of the opening has refrozen but the new ice is expected to be thinner and more fragile, and a new opening might appear during the melt season. This could make the ice in this region more mobile and prone to exiting the Arctic this summer through either the Fram or Nares straits, ultimately melting in the warmer waters of the Atlantic Ocean.

"This old, thicker ice is what we expect to provide stability to the Arctic sea ice system, since we expect that ice not to be as vulnerable to melting out as thinner, younger ice," said Alek Petty, a sea ice researcher at Goddard. "As ice in the Arctic becomes thinner and more mobile, it increases the likelihood for rapid ice loss in the summer."

Despite the fact that this year's melt season will begin with a low winter sea ice extent, this doesn't necessarily mean that we will see another record low summertime extent.

"A lot will depend on what the wind and temperature conditions will be in the spring and summer," Parkinson said.

Starting March 22, Operation IceBridge, NASA's aerial survey of polar ice, is flying over the Arctic Ocean to map the distribution and thickness of sea ice. In the fall, NASA will launch a new satellite mission, the Ice, Cloud and Land Elevation Satellite-2 (ICESat-2), which will continuously monitor how sea ice thickness is changing across the Arctic.

For NSIDC's analysis: http://nsidc.org/arcticseaicenews/2018/03/arctic-sea-ice-maximum-second-lowest/

Around 20% of the world's irrigated land is considered to contain elevated concentrations of salt, and the soil continues to get saltier as the climate warms. Agricultural production is hard hit by soil salinity; salt stress reduces the growth and yield of most plants, resulting in billions of dollars in crop yield losses annually. Rice--the staple food of more than half the world's population--is particularly sensitive to salty soil, with even moderate levels of salt resulting in substantial yield losses. There is thus an urgent need to develop rice lines that can withstand salty conditions.

A team of scientists led by Jian-Zhong Lin and Xuan-Ming Liu of Hunan University in Changsha, China recently identified a gene that contributes to salt stress tolerance in rice. The gene, which they named STRK1 (salt tolerance receptor-like cytoplasmic kinase 1), was activated under salt stress conditions. The researchers generated two sets of transgenic plants, one in which STRK1 was expressed at high levels, and the other in which expression was greatly reduced. Under regular growth conditions, both sets of transgenic plants appeared normal. However, when challenged with salt, the transgenic plants with elevated STRK1 expression were greener and larger than the non-transgenic control plants, and those with reduced levels of STRK1 expression were smaller and browner than the controls.

Next, the team examined the effect of STRK1 on yield. "Notably, overexpression of STRK1 in rice not only improved growth but also markedly limited the grain yield loss under salt stress conditions," said Jian-Zhong Lin.

The team then turned their attention to deciphering the mechanism by which STRK1 enhances the plant's tolerance to salt. Salt stress triggers the production of potentially harmful reactive oxygen species, such as hydrogen peroxide, in plant cells. The group found that STRK1 (the protein encoded by STRK1) interacts with and activates a protein named CatC, which belongs to a family of proteins that decomposes hydrogen peroxide into water and oxygen. Thus, STRK1 increases the plant's tolerance to salt stress by keeping the levels of hydrogen peroxide in check, and thereby minimizing the damage caused by accumulating reactive oxygen species.

These exciting findings bring the research community closer to developing rice plants that thrive in salty soil. "Agricultural productivity is increasingly threatened by the salinization of irrigated farmland...Our work demonstrates that STRK1 is a promising candidate gene for protection of yield in crop plants exposed to salt stress," stated Xuan-Ming Liu.

New research links specific numerical activities undertaken by parents to certain math skills in young children. Published today in open-access journal Frontiers in Psychology, the study also finds that the more parents engage in mathematical activities with their children, the higher their early numeracy performance.

Previous studies indicate that early mathematical skills provide a better transition to school-taught mathematics. It's well-known that parents can play an important role in their children's early mathematical development -- but, until now, the link between specific numerical activities and certain math skills was not well understood.

To shed light on these links, researchers from KU Leuven in Belgium assessed 128 kindergarten-age children for various symbolic and non-symbolic numerical tasks. The researchers also asked parents to indicate the frequency of certain numeracy activities undertaken with their children at home and then looked for connections between this and the children's early numeracy skills.

"We found that the more parents engaged in activities such as identifying numerals, sorting objects by size, color, or shape, or learning simple sums, the higher the children performed on skills like counting," says the study's lead author, Belde Mutaf Y?ld?z.

"These activities -- and talking about money when shopping or measuring ingredients while cooking -- were linked with a more accurate estimation of the position of a digit on an empty number line. In addition, engaging in activities such as card and board games was associated with better pictorial calculation skills."

Mutaf Y?ld?z says the research supports and extends the idea that parent-child interaction plays a role in children's acquisition of early mathematical skills -- and that policymakers should recognize this.

"Increased public awareness on the role that parents can play in their children's development of mathematical skills just by doing more number related activities in a home environment would be hugely useful," she says.

"Policymakers should think about providing educational tools for some home numeracy activities to help parents enhance their children's mathematical development."

The researchers caution that the study's findings are based on cross-sectional design and correlation analysis, meaning that the results don't indicate any cause-and-effect relationship. For example, it could be that children who are already good at mathematics are the ones triggering 'home numeracy' instead of their parents.

Despite this, with research on home numeracy in its infancy, Mutaf Y?ld?z and her colleagues are calling for more comprehensive investigations and observations of home numeracy activities, as well as further intervention studies to determine which specific activities best help children enhance their mathematical skills.

Barcelona, Spain: Extensive surgery involving mastectomy and removal of several lymph nodes can be safely avoided for more women with some types of breast cancer, if they receive targeted drugs before surgery, according to research presented at the 11th European Breast Cancer Conference.

The study focused on women with HER2 positive breast cancer, an aggressive form of the disease, who were given a targeted drug treatment to shrink their tumours before they had surgery.

Previous research has shown that women who have less extensive surgery suffer fewer long-term side-effects and enjoy better quality of life. The researchers say their work shows that even women with aggressive tumours can be safely treated with breast-conserving surgery, if the cancer responds to targeted treatment.

The research was led by Professor Isabel Rubio, Co-chair of the 11th European Breast Cancer Conference and former head of the breast surgical oncology unit at the breast cancer centre at Vall d'Hebron University Hospital in Barcelona, Spain, where she carried out the work.

She said: "In this study we have looked at women with HER2 positive breast cancer. This is an aggressive form of the disease but it is also one where a new class of drugs has successfully been developed. These drugs recognise and target HER2 receptors on the surface of cancer cells.

"We wanted to see whether the known benefits of these targeted drugs could be extended to spare women from the undesirable effects of radical surgery."

Surgery plays a vital role in treating breast cancer and it can involve removing only the area where the cancer is growing, or it can involve removing the whole breast as well as nearby lymph nodes, where the cancer may have spread. More extensive surgery is associated with more side effects such as pain and swelling that can last for many years.

The researchers studied a group of 160 women with HER2 positive breast cancer treated at Vall d'Hebron University Hospital between October 2007 and December 2016. Of these 129 (81%) were candidates for mastectomy based on the size of the tumour and other clinical characteristics.

All the patients were given a drug treatment before surgery including standard chemotherapy and at least one anti-HER2 drug such as trastuzumab (Herceptin ®).

As a result, 61 women (47.2%) who might otherwise have been offered mastectomy, were instead treated with less extensive surgery. This meant that overall 92 out of 160 women (57.5%) were treated with breast conserving surgery.

The treatment also resulted in 71% of women having no signs of cancer in their lymph nodes, meaning they could have less extensive surgery on their lymph nodes.

Professor Rubio explained: "This study shows us that treating HER2 positive breast cancer with a targeted drug before surgery can mean fewer women need to undergo mastectomy and removal of several lymph nodes. It also shows us that we can use biopsies to see which cancers are responding best to anti-HER2 treatments and therefore which patients can be safely treated with breast conserving surgery.

"Breast cancer treatments have advanced tremendously in recent years. What this means is that surgery should evolve too so that it is tailored to the individual patient and takes account of the effects of their particular treatment."

Professor Robert Mansel is chair of the 11th European Breast Cancer Conference and Emeritus Professor of Surgery at Cardiff University School of Medicine, UK, and was not involved in the research. He said: "Survival rates for breast cancer are improving and research continues to look for ways to build on that success. At the same time we need to understand the needs of individual patients and the differences between individual tumours.

"This research provides more information on which patients are likely to benefit from radical surgery and which could be safely treated with breast conserving surgery, bringing potential benefits in patients' of quality of life."

Barcelona, Spain: Professor Robert Mansel, Chair of the 11th European Breast Cancer Conference (EBCC-11) and Emeritus Professor of Surgery at Cardiff University School of Medicine, UK, has called for men to be included in trials to improve treatments for breast cancer.

Following new research presented by Professor Isabel Rubio [1] at EBCC-11 that showed that if women are pre-treated with targeted drugs to shrink tumours before surgery, they could avoid radical surgery, Prof Mansel said: "These findings could apply to men also, but we just don't know because men with breast cancer are almost never included in clinical trials.

"We need trials to start including men, so that we can discover whether or not they respond in the same way to targeted treatments as women. They may not, because the hormones involved in the cancer are different, but until this is investigated in trials, we do not know what is the best treatment for them.

"The cosmetic result after surgery is important for men too," he continued. "At present, men with breast cancer often undergo radical surgery to remove all the cancer, but why should surgeons remove the nipple and the areola, if it's not necessary? Men feel self-conscious about how this looks because if they want to swim or go to the beach their chests are uncovered if they wear swimming trunks. They could benefit from more conservative surgery that preserves the nipple and areola."

Breast cancer in men is 100 times less common than in women, with a lifetime risk of developing it of about one in 1,000 men. In the UK there are approximately 390 men diagnosed with breast cancer each year, compared to 54,800 cases in women. In the USA there were an estimated 2,240 new cases of and 410 deaths from male breast cancer in 2013.

The European Organisation for Research and Treatment of Cancer (EORTC), the Breast International Group (BIG) and the North American Breast Cancer Groups are coordinating an effort to analyse clinical data from a prospective international registry of male breast cancer patients. It will evaluate the number of patients that it is feasible to recruit for a future clinical trial, describe patterns of care, and assess sample collection rate. [2]

"This collaborative approach will be needed to perform reliable clinical trials in men," said Prof Mansel.

Prof Rubio, co-chair of EBCC-11, former head of the breast surgical oncology unit at the breast cancer centre at Vall d'Hebron University Hospital in Barcelona, and now director of the Breast Surgical Unit at Clinica Universidad de Navarra, Spain, presented her research to the conference on Friday. She described how extensive surgery involving mastectomy and removal of several lymph nodes could be safely avoided for more women with some types of breast cancer, if they received targeted drugs before surgery.

The study focused on women with HER2 positive breast cancer, an aggressive form of the disease, who were given a targeted drug treatment to shrink their tumours before they had surgery.

Previous research has shown that women who have less extensive surgery suffer fewer long-term side-effects and enjoy better quality of life. Prof Rubio said her work shows that even women with aggressive tumours can be safely treated with breast-conserving surgery, if the cancer responds to targeted treatment.

MISSOULA - A recent study from researchers at the University of Montana, National Audubon Society, Oregon State University and East Cascades Audubon Society shows food sources for migratory birds decline with low water levels and high salt content in lakes.

The study is based on data gathered for more than 25 years at Lake Abert in Oregon, one of the most important stops for migrating waterbirds in the western United States. It found that as surface water levels decline, salinity increases and affects the availability of brine shrimp and other invertebrates - a key food source for waterbirds.

According to the latest results of the study, Lake Abert has decreased by 618 acres - nearly 200 football fields in size - since 1986. The water levels have decreased due to water diversions for human uses, drought and a changing climate. During periods of low water and high salinity, bird sightings at Lake Abert declined by as much as 82 percent.

"Very few long-term studies of natural saline lake systems exist," said Nathan Senner, a postdoctoral fellow at UM.
"Our dataset is thus one of the few that can confirm what people have shown with laboratory experiments - once salinities become too high, it really has negative effects on both birds and invertebrates."

The study combines data on waterbird use, lake measurements and invertebrate abundance to document how waterbird numbers changed over 25 years in response to the changes in lake area, salinity and food sources.

Reduction in lake area and increase of salinity also has economic costs. One of the report's coauthors, Keith Kreuz, had to give up his business at Lake Abert due to uncertainty in the abundance of brine shrimp from year to year. Brine shrimp are used worldwide as a food source in commercial fish farming and for fish food in aquariums.

"We lost our 35-year-old brine shrimp business because of low lake levels, which resulted in toxic high salinity levels and ecosystem collapse," Kreuz said. "It is unfortunate because Lake Abert could help the local economy by supporting a thriving low-impact, sustainable fishery if only recently diverted water was once again allowed to flow into the lake."

Saline lakes, which provide critical habitats for migratory birds, are threatened globally and especially in the arid western United States. As lake levels diminish, so can bird populations. For some species, including Wilson's phalarope, eared grebe and American avocet, at least half of their global populations rely on this network of saline lakes for food and rest during migration. Some also nest in the region. Proper management of Lake Abert and other saline lakes in the West is critical to waterbird conservation in the Western Hemisphere.

"Water in the West is a precious resource, and there is urgent need to better understand and manage use of water throughout the region for the benefit of birds and people," said Stan Senner, vice president for bird conservation at the National Audubon Society.

For this study, waterbird data were drawn from the Bureau of Land Management and the East Cascades Audubon Society surveys, which used the time and efforts of dozens of community scientists to document changing bird numbers at Lake Abert.

"ECAS was pleased to work with community scientists to study the long-term effects of this beautiful lake and the birds that depend upon it," said John Reuland, volunteer coordinator for the Lake Abert study.

Scientists from Australia and China have drawn on the durable power of gold to demonstrate a new type of high-capacity optical disk that can hold data securely for more than 600 years.

The technology could offer a more cost-efficient and sustainable solution to the global data storage problem while enabling the critical pivot from Big Data to Long Data, opening up new realms of scientific discovery.

The recent explosion of Big Data and cloud storage has led to a parallel explosion in power-hungry data centres. These centres not only use up colossal amounts of energy - consuming about 3 per cent of the world's electricity supply - but largely rely on hard disk drives that have limited capacity (up to 2TB per disk) and lifespans (up to two years).

Now scientists from RMIT University in Melbourne, Australia, and Wuhan Institute of Technology, China, have used gold nanomaterials to demonstrate a next-generation optical disk with up to 10TB capacity - a storage leap of 400 per cent - and a six-century lifespan.

VIEW AND EMBED THE VIDEO: https://youtu.be/DylDNsqdAmI

The technology could radically improve the energy efficiency of data centres - using 1000 times less power than a hard disk centre - by requiring far less cooling and doing away with the energy-intensive task of data migration every two years. Optical disks are also inherently far more secure than hard disks.

Lead investigator, RMIT University's Distinguished Professor Min Gu, said the research paves the way for the development of optical data centres to address both the world's data storage challenge and support the coming Long Data revolution.

"All the data we're generating in the Big Data era - over 2.5 quintillion bytes a day - has to be stored somewhere, but our current storage technologies were developed in different times," Gu said.

"While optical technology can expand capacity, the most advanced optical disks developed so far have only 50-year lifespans.

"Our technique can create an optical disk with the largest capacity of any optical technology developed to date and our tests have shown it will last over half a millennium.

"While there is further work needed to optimise the technology - and we're keen to partner with industrial collaborators to drive the research forward - we know this technique is suitable for mass production of optical disks so the potential is staggering."

The world is shifting from Big Data towards Long Data, which enables new insights to be discovered through the mining of massive datasets that capture changes in the real world over decades and centuries.

Lead author, Senior Research Fellow Dr Qiming Zhang from RMIT's School of Science, said the new technology could expand horizons for research by helping to advance the rise of Long Data.

"Long Data offers an unprecedented opportunity for new discoveries in almost every field - from astrophysics to biology, social science to business - but we can't unlock that potential without addressing the storage challenge," Zhang said.

"For example, to study the mutation of just one human family tree, 8 terabytes of data is required to analyse the genomes across 10 generations. In astronomy, the Square Kilometre Array (SKA) radio telescope produces 576 petabytes of raw data per hour.

"Meanwhile the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to 'map' the human brain is handling data measured in yottabytes, or one trillion terabytes.

"These enormous amounts of data have to last over generations to be meaningful. Developing storage devices with both high capacity and long lifespan is essential, so we can realise the impact that research using Long Data can make in the world."

The novel technique behind the technology - developed over five years - combines gold nanomaterials with a hybrid glass material that has outstanding mechanical strength.

The research progresses earlier groundbreaking work by Gu and his team that smashed through the seemingly unbreakable optical limit of blu-ray and enabled data to be stored across the full spectrum of visible light rays.

How it works

The researchers have demonstrated optical long data memory in a novel nanoplasmonic hybrid glass matrix, different to the conventional materials used in optical discs.

Glass is a highly durable material that can last up to 1000 years and can be used to hold data, but has limited storage capacity because of its inflexibility.

The team combined glass with an organic material, halving its lifespan but radically increasing capacity.

To create the nanoplasmonic hybrid glass matrix, gold nanorods were incorporated into a hybrid glass composite, known as organic modified ceramic.

The researchers chose gold because like glass, it is robust and highly durable. Gold nanoparticles allow information to be recorded in five dimensions - the three dimensions in space plus colour and polarisation.

The technique relies on a sol-gel process, which uses chemical precursors to produce ceramics and glasses with better purity and homogeneity than conventional processes.

Use of certain diabetes drugs, known as dipeptidyl peptidase-4 inhibitors, is associated with an increased risk of inflammatory bowel disease, the digestive condition that causes stomach pain and bloating, finds a study published by The BMJ today.

The researchers stress that the absolute risk is low - and that their findings need to be replicated - but say "physicians should be made aware of this possible association."

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a relatively new type of diabetes drug that lower high blood sugar levels. They are usually prescribed for people with type 2 diabetes who have not responded well to other drugs.

They work by blocking the DPP-4 enzyme that is involved in the body's inflammatory response and regulates gut hormones. Some data suggest that lower serum levels of DPP-4 enzyme may be linked to increased disease activity in patients with inflammatory bowel disease, but no study has investigated the impact of inhibiting this enzyme on the occurrence of this disease.

So a Canadian team, led by Laurent Azoulay at McGill University, set out to assess whether the use of DPP-4 inhibitors is associated with inflammatory bowel disease in patients with type 2 diabetes.

They analysed data from the UK's Clinical Practice Research Database for 141,170 patients aged at least 18 years of age, who were starting antidiabetic drugs between 2007 and 2016.

Patients initially treated with insulin and those with a history of inflammatory bowel disease or similar conditions were excluded. Factors such as age, weight (BMI), smoking status, alcohol related disorders and complications of diabetes were taken into account.

Participants were monitored for an average of three and a half years, during which time 208 new cases of inflammatory bowel disease were recorded (an incidence rate of 37.7 per 100,000 person years).

Overall, use of DPP-4 inhibitors was associated with a 75% increased risk of inflammatory bowel disease (53.4 cases per 100,000 person years) compared with use of other antidiabetic drugs (34.5 cases per 100,000 person years).

This association gradually increased with longer durations of DPP-4 inhibitor use, reaching a peak after three to four years and decreasing after more than four years of use.

Although no single DPP-4 inhibitor drug was statistically associated with inflammatory bowel disease, these findings remained unchanged after further analyses to test the strength of the results.

This is an observational study, so no firm conclusions can be drawn about cause and effect, and the researchers point to some limitations, such as possible misclassification of drugs or cases. And while they adjusted for several risk factors, they cannot rule out the possibility that other unmeasured (confounding) factors may have influenced the results.

Nevertheless, they say in this first population based study, the use of dipeptidyl peptidase-4 inhibitors was associated with an increased risk of inflammatory bowel disease.

"Although our findings need to be replicated, physicians should be aware of this possible association and perhaps refrain from prescribing DPP-4 inhibitors for people at high risk, such as those with a family history of disease or with known autoimmune conditions," they conclude.

Alexandria, VA, USA - At the 47th Annual Meeting of the American Association for Dental Research (AADR), held in conjunction with the 42nd Annual Meeting of the Canadian Association for Dental Research (CADR), Alen Blagajcevic, student at Tufts University School of Dental Medicine, Boston, Mass., presented an oral session titled "Bioengineered Tooth Bud Model Functionalized With Decellularized Tooth Bud ECM." The AADR/CADR Annual Meeting is in Fort Lauderdale, Fla., USA from March 21-24, 2018.

Researchers aimed to create 3D bioengineered tooth buds to serve as a biologically based replacement tooth alternative to current dental implants. Gelatin Methacrylate (GelMA) hydrogel can be used to encapsulate postnatal dental stem cells (DSC) and support odontogenic differentiation and mineralized tissue formation.

Blagajcevic's work is done under the direction of Pamela Yelick, Ph.D., professor of orthodontics and director of the division of craniofacial and molecular genetics at Tufts University School of Dental Medicine, whose research has long-focused on creating biological-tooth replacements.

"To enhance enamel and dentin matrix production, we have created functionalized bioengineered GelMA tooth buds with decellularized tooth bud extracellular matrix (dTB ECM)" said Alen Blagajcevic. "The Yelick lab at Tufts had previously determined that dTBs retain ECM components known to play important roles in dental cell proliferation, differentiation, and tooth morphogenesis. Upon in vivo implantation, cell-seeded dTB scaffolds formed whole tooth structures. In this study, we introduced lyophilized dTB ECM to our bioengineered GelMA tooth bud model." "We found that dTB ECM powder can be used to enhance DSC differentiation in GelMA tooth bud constructs," said Alen Blagajcevic. "These promising but preliminary results suggest that dTB ECM can be used to enhance dental stem cells DSC proliferation and differentiation, advancing the GelMA tooth bud model towards future clinical applications." The Yelick Lab at Tufts is funded by the National Institute of Dental and Craniofacial Research of the National Institutes of Health (award numbers R01DE026731 and R01 DE016132, both to PCY).

James Cook University (JCU) scientists in Australia have found high carbon dioxide levels cause squid to bungle attacks on their prey.

PhD candidate Blake Spady from JCU's ARC Centre of Excellence for Coral Reef Studies led the investigation. He said that the oceans absorb over one-quarter of all the excess carbon dioxide (CO2) released into the atmosphere by humans and this uptake of additional CO2 causes seawater to become more acidic.

"Climate models project that unless there is a serious commitment to reducing emissions, CO2 levels will continue increasing this century to reach levels that will have far-reaching effects on sea life," he said.

Mr Spady said the team chose to study cephalopods (a group that includes squid, cuttlefish and octopuses) because most previous behavioural studies have focused on fishes, and the effects of elevated CO2 on highly active invertebrates is largely unknown.

"Cephalopods also prey on just about anything they can wrap their arms around and are themselves preyed upon by a wide range of predator species, so they occupy an important place within marine food webs."

The scientists tested the effects of elevated CO2 on the hunting behaviours of pygmy squid and bigfin reef squid.

"For pygmy squid, there was a 20% decrease in the proportion of squid that attacked their prey after exposure to elevated CO2 levels. They were also slower to attack, attacked from further away, and often chose more conspicuous body pattern displays at elevated CO2 conditions.

Bigfin reef squid showed no difference in the proportion of individuals that attacked prey, but, like the pygmy squid, they were slower to attack and used different body patterns more often."

Mr Spady said both species showed increased activity at elevated CO2 conditions when they weren't hunting, which suggests that they could also be adversely altering their 'energy budgets'.

"Overall, we found similar behavioural effects of elevated CO2 on two separate cephalopod orders that occupy largely distinct niches. This means a variety of cephalopods may be adversely affected by rising CO2 in the oceans, and that could have significant consequences in marine ecosystems," said co-author Dr Sue-Ann Watson.

"However, because squid have short lifespans, large populations, and a high rate of population increase, they may have the potential to adapt to rapid changes in the physical environment," Mr Spady added.

"The fast lifestyle of squid could mean they are more likely to adapt to future ocean conditions than some other marine species, and this is the next question we intend to investigate."

When a doctor or nurse suspects something is wrong with a patient's heart, there's a simple way to check: put a stethoscope over the heart and listen to the sounds it makes. Doctors and nurses can use the same diagnostic tool to figure out what's going on with the lungs, stomach and more, but not the brain - although that could change with a new device.

Over the past several years, Stanford neurologists have been working with a specialist in computer music to develop a brain stethoscope - not a stethoscope per se, but rather an algorithm that translates the brain's electrical activity into sounds.

Now, the same team has shown that medical students and nurses - non-specialists, in other words - can listen to the brain stethoscope and reliably detect so-called silent seizures - a neurological condition in which patients have epileptic seizures without any of the associated physical convulsions. The group published the work March 21 in the journal Epilepsia.

"This technology will enable nurses, medical students and physicians themselves to actually assess their patient right there and they will be able to determine if the patient is having silent seizures," said Josef Parvizi, a professor of neurology and neurological sciences.

Seizures of a different sort

The desire for a brain stethoscope stems from a basic problem with treating epileptic seizures - namely, a great many of them may go undetected and untreated.

Technically, a seizure is a neurological problem, in which ordinarily calm electrical brain waves go haywire. That erratic activity can cause convulsions - but not always.

"You might think that all seizures must cause some sort of convulsions, namely a patient who's having a seizure must fall down and shake on the ground. But that's actually not the case, especially in critically ill patients in the intensive care units," said Parvizi, who is also a member of Stanford Bio-X, the Stanford Neurosciences Institute and the Child Health Research Institute. "Close to 90 percent of those patients will have silent seizures," he said, and though not visible they can still damage the brain if they are prolonged.

On top of that, diagnosing silent seizures can be a drawn-out process, even during regular hours at a major hospital like Stanford's. First, a trained technician comes in, sets up sensors on a patient's skull to record the brain's electrical activity, then makes a recording and sends it to a neurology specialist like Parvizi for analysis. By the time the diagnosis comes in, hours may have passed. After hours or in smaller hospitals, the process can take even longer - for one thing, a technician may have to come from hours away just to set up the equipment.

Music of the mind

The solution came, Parvizi said, after watching Kronos Quartet perform a piece of music based on data recorded by a scientific instrument aboard the Voyager space probe. Parvizi realized something similar could be done with brain waves, so he sent some data files to Chris Chafe, the Duca Family Professor and a professor of music.

"I had never even entertained the idea that we would attach some of my music synthesis to somebody's head," said Chafe, who is also a member of Bio-X and the Neurosciences Institute. But it wasn't particularly odd either - Chafe has also made music out of climate change data and the carbon dioxide generated by ripening tomatoes. In this case, he used brain-wave data to modulate the singing sounds of a computer-synthesized voice - a natural choice, Chafe said, given the context.

"Once he sent me the files and I listened to them, I was literally in shock, because it was so intuitive," Parvizi said. "You could hear the transition from non-seizure to seizure so easily, that I just basically picked up the phone and told Chris that we have something right here."

So easy a medical student can do it

But Parvizi is a trained neurologist, and to really test the potential of a brain stethoscope he needed to see if non-specialists could hear the difference between normal brain activity and a seizure. With the help of a Bio-X seed grant, Kapil Gururangan, a medical student, and Babak Razavi, a clinical assistant professor of neurology, gathered 84 brain wave samples, called electroencephalograms or EEGs, 32 of which included either a seizure or some features typical of one. Then, they turned those samples into music using Chafe's algorithm and played them for 34 medical students and 30 nurses at Stanford.

Despite having no training in the diagnosis of epilepsy, medical students and nurses were remarkably good at discerning seizures and seizure-like events from normal brain waves. "The ability of an untrained medical student or nurse to read an EEG is pretty dismal -- it's 50 percent," Gururangan said. But by listening to that EEG transformed into sound, medical students and nurses could accurately detect seizures more than 95 percent of the time.

Medical students and nurses also correctly identified samples with seizure-like features about three-quarters of the time and they correctly identified normal activity at similar rates - not perfect, but not bad either, given their training, Gururangan said.

"The question now that we have to figure out is: How are actual physicians going to use this tool and how do physicians use this information in their decision-making?" Gururangan said. In other words, the team has a number of questions it is still looking to answer, but the early results sound good.