Culture

Diabetic patients are more likely to die from alcohol-related factors, accidents or suicide, according to a study published in the European Journal of Endocrinology. The study findings suggest that the increased risk of death from these causes may be related to the mental health of patients, which may be adversely affected by the psychological burden of living with and self-treating this debilitating disease, with potentially serious complications.

Type-1 and type-2 diabetes are highly prevalent global diseases, causing millions of deaths every year. It is well known that diabetic patients have a higher risk of developing cardiovascular disease, cancer and kidney disorders, which can lead to earlier death. However, more recently diabetes has been linked to an increased risk of depression but how poor mental health may affect patients with diabetes has not been fully investigated.

In this nationwide Finnish study, Professor Leo Niskanen and colleagues, from the University of Helsinki and Tampere and Helsinki University Hospital, assessed the alcohol-related, suicides or accidental causes of death of over 400,000 people with or without diabetes. The study reported that people with diabetes were much more likely to die from alcohol-related factors, accidents or suicide, especially patients that required regular, self-injections of insulin.

Prof Leo Niskanen comments, "We know that living with diabetes can lead to a mental-health strain. Having to monitor their glucose levels and inject themselves daily with insulin has a huge impact on daily life; simply eating, moving and sleeping all affect blood glucose levels. This strain combined with the anxiety of developing serious complications like heart or kidney disease may also take their toll on psychological well-being."

Prof Leo Niskanen states, "This study has highlighted that there is a need for effective psychological support for people with diabetes. If they feel like they are under a heavy mental burden or consider that their use of alcohol is excessive, they should not hesitate to discuss these issues with their primary care physician. There are many ways that these problems can be managed, provided they are communicated."

The team now plans to carry out a more in depth investigation of the risk factors and mechanisms underpinning these findings to help identify strategies to avoid future deaths. In addition, the influence of drugs such as antidepressants, the occurrence of diabetic complications such as low blood glucose, or the socioeconomic status of patients will also be considered.

Researchers have demonstrated an integrated technique for monitoring specific biomolecules - such as growth factors - that could indicate the health of living cell cultures produced for the burgeoning field of cell-based therapeutics.

Using microfluidic technology to advance the preparation of samples from the chemically complex bioreactor environment, the researchers have harnessed electrospray ionization mass spectrometry (ESI-MS) to provide online monitoring that they believe will provide for therapeutic cell production the kind of precision quality control that has revolutionized other manufacturing processes.

"The way that the production of cell therapeutics is done today is very much an art," said Andrei Fedorov, Woodruff Professor in the George W. Woodruff School of Mechanical Engineering at the Georgia Institute of Technology. "Process control must evolve very quickly to support the therapeutic applications that are emerging from bench science today. We think this technology will help us reach the goal of making these exciting cell-based therapies widely available."

By measuring very low concentrations of specific compounds secreted or excreted by cells, the technique could also help identify which biomolecules - of widely varying sizes - should be monitored to guide the control of cell health. Ultimately, the researchers hope to integrate their label-free monitoring directly into high-volume bioreactors that will produce cells in quantities large enough to make the new therapies available at a reasonable cost and consistent quality.

Development of the Dynamic Mass Spectrometry Probe (DMSP) was supported by the National Science Foundation (NSF) Engineering Research Center for Cell Manufacturing Technologies (CMaT), which is headquartered at Georgia Tech. The work was reported September 10 in the journal Biotechnology and Bioengineering.

Traditional ESI-MS techniques have revolutionized analytical chemistry by allowing precise identification of complex biological compounds. Because of complex sample preparation requirements, existing approaches to ESI-MS require too much time to be useful for continuous monitoring of cell growth in bioreactors, where maintaining narrow parameters for specific indicators of cellular health is critical. Biological samples also contain salts, which must be removed before introduction into the ESI-MS system.

To accelerate the analytical process, Fedorov and a team that included graduate research assistant Mason Chilmonczyk and research engineer Peter Kottke used microfluidic technology to help separate compounds of interest from the salts. Salt removal uses a monolithic device in which a size-selective membrane with nanoscale pores is placed between two fluid flows, one the chemically complex sample drawn from the bioreactors and the other salt-free water with conditioning compounds.

The smaller salt molecules readily diffuse out of the sampled bioreactor flow through the nanopores, while the larger biomolecules mostly remain for the subsequent ESI-MS analysis. Meanwhile, chemical additives are at the same time introduced into the sample mixture through the same membrane nanopores to enhance ionization of the target biomolecules in the sampled mixture for improved ESI-MS analysis.

"We have used advanced microfabrication techniques to create a microfluidic device that will be able to treat samples in less than a minute," said Chilmonczyk. "Traditional sample preparation can require hours to days."

The process can currently remove as much as 99 percent of the salt, while retaining 80 percent of the biomolecules. Introduction of the conditioning chemicals allows the molecules to accept a greater charge, improving the capability of the mass spectrometer to detect low concentration biomolecules, and to measure large molecules.

"We can detect really high molecular weight molecules that the mass spectrometer normally wouldn't be able to detect," Fedorov said. "The size difference in the molecules of interest can be dramatic, so the improvement in the limit of detection across a broad range of analyte molecular weights will allow this technique to be more useful in cell manufacturing."

Because they use state of the art microfabrication techniques, the DMSP devices can be mass produced, allowing sampling to be scaled up to include multiple bioreactors at low cost. The small size of the device channels - which are just five microns tall - allows the system to produce results with samples as small as 20 nanoliters - with the potential for reducing that to as little as a single nanoliter.

"We need to monitor small concentrations of large biomolecules in this messy environment in a production line in such a way that we can check at any point how the cells are doing," Fedorov said. "This system could continuously monitor whether certain molecules are excreted or secreted at a reduced or increased rate. By correlating these measurements with cell health and potency, we could improve the manufacturing process."

Before the analytical techniques can be applied to quality control, the researchers must first identify biomolecules that indicate health of the growing cells. By sampling the bioreactor content locally in the immediate vicinity of cells and allowing identification of very small quantities of biochemicals, the DMSP technology can help researchers identify changes in molecular concentrations - which range from pico-molar to micro-molar - that may indicate the state of cells in the bioreactors. This would prompt adjustment of conditions in a bioreactor just in time to return to the state of healthy cell growth.

"In this situation, we often can't see the trees for the forest," said Fedorov. "There is a lot of material available, but we are looking for just a handful of individual trees that indicate the health of the cells. Because the forest is overgrown, the few selected trees we need to examine are hard to find. This is a grand challenge technologically."

A research team has discovered that abnormal vision in childhood can affect the development of higher-level brain areas responsible for things such as attention.

The researchers from the University of Waterloo, University of British Columbia, and the University of Auckland uncovered differences in how the brain processes visual information in patients with various types of lazy eye. In doing so, they are the first to demonstrate that the brain can divert attention away from a lazy eye when both eyes are open.

"Current treatments for lazy eye primarily target the early stages of visual processing within the brain," said Ben Thompson, a professor in Waterloo's School of Optometry and Vision Science."The results from this study show us that new treatments should also target higher-level processes such as attention."

Lazy eye, known as amblyopia, is a loss of vision that originates in the brain, typically when a child develops an eye turn (strabismic type) or a substantial difference in refractive error between the eyes (anisometropic type). The unequal input causes the brain to ignore information from the weaker eye during brain development. Conventionally, eyecare practitioners treated the different types of lazy eye similarly, primarily because the visual impairments experienced appeared to be the same.

In this study lead researcher, Amy Chow, and her colleagues asked patients to pay attention to a specific set of dots among a group of distracting dots, all moving on a computer screen. However, the tracked dots were only visible in one eye (the weaker eye) while the distracting dots were visible only to the other eye (the stronger eye).

For people with normal vision as well as those with anisometropic amblyopia, showing different images between the two eyes didn't matter. Both groups were able to overcome the distracting interference and track the dots successfully. Patients with strabismic amblyopia, on the other hand, were unable to direct their attention to the target dots when they were visible to only the weaker eye.

"One of the underlying reasons why some people with lazy eye have poor vision comes down to how the brain suppresses an eye," said Chow, a PhD student at the School of Optometry and Vision Science at Waterloo. "The poorer-seeing eye is open, the retina is healthy and sending information through to the brain, yet that information does not reach conscious awareness as the brain chooses not to use it."

About thirty-five thousand Canadians - one per cent of the population - have strabismic amblyopia. The condition can be corrected in childhood, but treatment efficacy can be highly variable. These findings are a stepping stone in developing better treatments of lazy eye.

The brain's crucial function is to allow organisms to learn and adapt to their surroundings. It does this by literally changing the connections, or synapses, between neurons, strengthening meaningful patterns of neural activity in order to store information. The existence of this process - brain plasticity - has been known for some time.

But actually, there are two different types of brain plasticity at work on synapses. One is "Hebbian plasticity"; it is the one which effectively allows for the recording of information in the synapses, named after pioneering neuroscientist Donald Hebb. The other, more recently discovered, is "homeostatic synaptic plasticity" (HSP), and, like other "homeostatic" processes in the body such as maintaining a constant body temperature, its purpose is to keep things stable. In this case, HSP ensures that the brain doesn't build up too much activity (as is the case in epilepsy) or become too quiet (as can happen when you lose synapses in Alzheimer's Disease).

However, little is known about how these two types of plasticity actually interact in the brain. Now, a team of neuroscientists at the Champalimaud Centre for the Unknown, in Lisbon, Portugal, has begun to unravel the fundamental processes that happen in the synapse when the two mechanisms overlap. Their results were published in the journal iScience.

"In theory, the two types of plasticity act as opposing forces", says Anna Hobbiss, first author of the new study, which was led by Inbal Israely. "Hebbian plasticity reacts to activity at the synapses by inciting them to get stronger while HSP reacts to it by making them weaker. We wanted to understand, on a cellular and molecular level, how the synapse deals with these two forces when they are present at the same time."

In so doing, the authors have surprisingly shown that, contrary to what might be expected, HSP facilitates Hebbian plasticity, and thus influences memory formation and learning. This means that these two types of plasticity "may actually not be such distinct processes, but instead work together at the same synapses", says Israely.

The team's goal was to determine the changes in size of minute structures called dendritic spines, which are the "receiving end" of the synapse. The size of these spines changes to reflect the strength of the synaptic connection.

For this, they studied cells from the mouse hippocampus, a part of the brain which is crucial for learning. In their experiments, they blocked activity in the cells by introducing a potent neurotoxin called tetrodotoxin, thus simulating the loss of input to a certain part of the brain ("think about a person suddenly becoming blind, which leads to loss of input from the eyes to the brain", says Hobbiss).

Forty eight hours later, they mimicked a small recovery of activity at only one synapse by releasing a few molecules of a neurotransmitter called glutamate on single spines of single neurons. This was possible thanks to a very high resolution, state-of-the-art laser technology, called two-photon microscopy, which allowed the scientists to very precisely visualize and target individual dendritic spines.

As this process evolved, the team closely watched what was happening to the spines - and they saw various anatomical changes. First, the silencing of all neural activity made the spines grow in size. "The spines are like little microphones, which, when there is silence, ramp up the 'volume' to try and catch even the faintest noise", Hobbiss explains.

The scientists then activated individual spines with pulses of glutamate and watched them for two hours. One of the things they thought could happen was that the size of the spines would not grow further, since they had already turned up their 'volume' as far is it would go. But the opposite happened: the spines grew even more, with the smaller spines showing the biggest growth.

Finally, the authors also saw growth in neighboring spines, even though the experiment only targeted one spine. "We found that after a lack of activity, other spines in the vicinity also grew, further enhancing the cell's sensitivity to restored neural transmission", says Hobbiss. "The cells become more sensitive, more susceptible to encode information. It is as though the 'gain' has been turned up", she adds.

"The fact that neighboring spines grew together with an active spine signifies that homeostatic plasticity changes one of the hallmark features of information storage, which is that plasticity is limited to the site of information entry", Israely explains. "So, in this sense, the different plasticity mechanisms which are at work in the neuron can cooperate to change which and how many inputs respond to a stimulus. I think this is an exciting finding of our study."

Taken together, these results show that homeostatic plasticity can actually rev up Hebbian plasticity, the type required for storing information. "Our work adds a piece to the puzzle of how the brain performs one of its fundamental tasks: being able to encode information while still keeping a stable level of activity", concludes Hobbiss.

The misregulation of homeostatic plasticity - the stabilizing one - has started to be implicated in human health, specifically neurodevelopmental disorders such as Fragile X syndrome and Rett syndrome as well as neurodegenerative ones such as Alzheimer's Disease. "Perhaps this balance is what allows us to be able to learn new information while retaining stability of that knowledge over a lifetime", says Israely.

World energy consumption projections expect coal to stay one of the world's main energy sources in the coming decades, and a growing share of it will be used in CTL, the conversion of coal to liquid fuels. Researchers from the National Institute of Clean-and-Low-Carbon Energy in Beijing and Eindhoven University of Technology have developed iron-based catalysts that substantially reduce operating costs and open the door to capturing the large amounts of CO2 that are generated by CTL. Their results are published in the journal Science Advances.

To understand the significance of this achievement, some knowledge of the CTL process is required. The first stage is the conversion of coal to syngas, a mixture of carbon monoxide (CO) and hydrogen (H2). Using the so-called Fischer-Tropsch process, these components are converted to liquid fuels. But before that can be done, the composition of the syngas has to be changed to make sure the right products come out in the end - liquid fuels. So some of the CO is taken out of the syngas (rejected) by converting it to CO2, in a process called 'water-gas shift'.

In this chain the researchers tackled a key problem in the Fischer-Tropsch reactor. As in most chemical processing, catalysts are required to enable the reactions. CTL catalysts are mainly iron based. Unfortunately, they convert some 30 percent of the CO to unwanted CO2, a byproduct that in this stage is hard to capture and thereby often released in large volumes, consuming a lot of energy without benefit.

The Beijing and Eindhoven researchers discovered that the CO2 release is caused by the fact that the iron based catalysts are not pure, but consist of several components. They were able to produce a pure form of a specific iron carbide, called epsilon iron carbide, that has a very low CO2 selectivity. In other words, it generates almost no CO2 at all. The existence was already known but until now it had not been stable enough for the harsh Fischer-Tropsch process. The Sino-Dutch research team has now shown that this instability is caused by impurities in the catalyst. The phase-pure epsilon iron carbide they developed is, by contrast, stable and remains functional, even under typical industrial processing conditions of 23 bar and 250oC.

The new catalyst eliminates nearly all CO2 generation in the Fischer-Tropsch reactor. This can reduce the energy needed and the operating costs by roughly 25 million euros per year for a typical CTL plant. The CO2 that was previously released in this stage can now be removed in the preceding water-gas shift stage. That is good news, because it is much easier to capture in this stage. The technology to make this happen is called CCUS (carbon capture, utilization and storage). It has been developed by other parties and is already being applied in several pilot plants.

The conversion of coal to liquid fuels is especially relevant in coal-rich countries that have to import oil for their supply of liquid fuels, such as China and the US. "We are aware that our new technology facilitates the use of coal-derived fossil fuels. However, it is very likely that coal-rich countries will keep on exploiting their coal reserves in the decades ahead. We want to help them do this in the most sustainable way," says lead researcher professor Emiel Hensen of Eindhoven University of Technology.

The research results are likely to reduce the efforts to develop CTL catalysts based on cobalt. Cobalt based catalysts do not have the CO2 problem, but they are expensive and quickly becoming a scarce resource due to cobalt use in batteries, which account for half of the total cobalt consumption.

Hensen expects that the newly developed catalysts will also play an import role in the future energy and basic chemicals industry. The feedstock will not be coal or gas, but waste and biomass. Syngas will continue to be the central element, as it is also the intermediate product in the conversion of these new feedstocks.

Almost eight years ago, Stanford University bioengineer Manu Prakash was looking for a way to watch every cell in an adult living, behaving animal in elaborate detail. He searched the catalog of life and happened upon the simple marine animal Trichoplax adhaerens - or Tplax, as Prakash has come to call it.

This ultra-flat animal lacks both muscles and neurons, but still moves and navigates through its watery world. The Prakash lab found Tplax manages this feat through surprisingly fast contractions in its two skin-like layers - contractions strong enough that they would ordinarily rip apart such seemingly delicate tissues. In their first paper based on years-long study of this organism, published Oct. 11 in Proceedings of the National Academy of Sciences, the researchers describe the ultra-fast contractions and propose a hypothesis for how this creature withstands internal and external forces in a marine environment.

The findings could help inform not only how complex animals evolved, but also the creation of an advanced material, called an active solid, that could dramatically and quickly modulate its own physical properties.

"Much of the rules of biology that we read in textbooks have been, so far, dictated by a few sets of 'model' organisms," said Prakash, who is an associate professor of bioengineering and senior author of the paper. "If we intend to be the generation that will unravel laws of biology, it's extremely important to understand and appreciate the diversity of what has evolved on our planet and think much more holistically about what is actually possible in biological systems."

Moving without muscles

In the early days of studying Tplax, the creatures would move repeatedly out of view under the microscope. But over time, the Prakash lab researchers learned to track and quantify the animals' every cellular squeeze and squirm. Prakash remembers when their efforts first began to pay off.

"There was literally a day where, for the first time, I had some of the stains that label Tplax cells working, and under the microscope we saw an explosion of cellular contractions," said Prakash. "It looked like fireworks under a microscope and that was the moment that told us there is something very special about this animal and we needed to understand it."

Those fireworks were Tplax's quick contractions, which occur in its flat layer of what are known as epithelial cells - essentially the equivalent of skin. Although these kinds of cells have long been known to contract, in embryos for example, Tplax's contractions were 10 times faster than any epithelial cell contraction ever reported. This would tear apart the network of cells in any other biological tissue as thin as this animal, which is only about 25 microns thick, or one-quarter the thickness of a sheet of paper.

The researchers think the tissue's strength lies in the fact that while some cells contract strongly, others soften - a hypothesis they call "active cohesion." In many tissues, contracting in reaction to a force would cause a tear and relaxing would cause the animal to be at the mercy of that force. By doing both simultaneously and in a coordinated manner, the cells involved in Tplax's active cohesion distribute the stress, letting the animal remain whole and in control.

The discovery of an ultra-fast contractile epithelial cell poses new questions for the role of epithelial contractions in coordinating cellular activity across the tissue.

"We look at this simple creature and we see it make decisions and move and hunt," said Shahaf Armon, a postdoctoral fellow in the Prakash lab who is lead author of the paper. "It's a huge evolutionary question, how single cells merged to become multicellular organisms and how such a minimal tissue made of identical cells is able to then perform complex behaviors."

Now, the researchers are exploring what other organisms might use active cohesion and are creating artificial material that replicates this mechanism to build an active solid. Key to the speed of these contractions is the unusual geometry of Tplax's epithelial structure: T-shaped cells with a very thin top sheet and a hanging nucleus at the bottom that line up side-by-side like a single layer of bricks. That geometry, which they share with sponges, could inform the development of new materials.

Mysterious beasts

Working with laboratory lineages and animals they caught themselves in Monterey, the group grew Tplax in a wide variety of sizes and shapes, creating animals that are hundreds to millions of cells. This variation in size provides a powerful window into understanding how cellular coordination varies as the number of cells increase or decrease.

"Tplax are really mysterious beasts," said Matthew Bull, a graduate student in the Prakash lab and co-author of the paper, "but we use that to our advantage to find where our understanding of what it means to be part of the animal kingdom bends and then breaks."

Did prehistoric sea creatures called mosasaurs subdue prey by ramming them with their bony snouts like killer whales do today?

It's a theory that University of Cincinnati biology professor Takuya Konishi proposed after taking a closer look at a newborn fossil specimen for his latest research study. Konishi will present his findings at October's Society of Vertebrate Paleontology conference in Albuquerque, New Mexico.

"Killer whales don't hunt big prey by biting. They hunt by ramming and tearing them apart after the prey is weak," Konishi said. "They are chasing fast-moving animals so they use inertia. If they were swimming full speed at you, they would generate a lot of force. And their snout is conspicuously protruding."

Mosasaur, the unlikely hero of the movie "Jurassic World," was an enormous marine reptile that lived in the time of Tyrannosaurus rex during the Cretaceous Period more than 65 million years ago. They had a similar body shape as today's orcas, with flippers, powerful tails and sharp teeth. Some grew bigger than orcas to nearly the size of a school bus.

Like orcas, they were the apex predators of the seas. The only thing mosasaurs had to fear were bigger mosasaurs.

In a study published this month in the Journal of Vertebrate Paleontology, Konishi re-examined fossils of a newborn mosasaur he first studied in Kansas while working on his master's degree in 2004. About 20 small fragments of skull were unearthed in 1991 by paleontologist Michael Everhart in a rock formation called the Kansas Chalk renowned for marine fossils.

Initially, the specimen was identified as a mosasaur called Platecarpus, a species commonly found in that area during the same period 85 million years ago. The family Mosasauridae features more than 30 genera of species, so identifying a particular specimen from a handful of fossil fragments can be daunting.

"A colleague of mine told me mosasaurs are boring because they all look the same. That's sort of true," he said. "But once you know more about them you can begin to tell them apart."

Some mosasaurs had short, powerful jaws capable of crushing the shells of sea turtles. Others had pointy teeth that suggested they feed mostly on fish.

Konishi was inspired to take a second look after a fellow researcher demonstrated how particular bones called quadrates were not as reliable in identifying species as researchers once thought. The telltale fossils of adults of different species look very similar in juveniles.

In the many years since Konishi first examined the baby mosasaur, he has become an expert on these seagoing lizards, including the largest of them called Tylosaurus. This was the creature that inspired "Jurassic World," a meat-eating monster capable of hunting other mosasaurs and marine reptiles.

In re-examining the skull fragments from the newborn mosasaur, Konishi found it did not resemble other specimens of Platecarpus. While Platecarpus and other mosasaurs have teeth that begin virtually at the tip of their snouts, Tylosaurus has a bony protrusion called a rostrum that extends out from its face like an orca that might have served to protect its front teeth when they slammed into prey.

"It's a subtle feature perhaps by horned dinosaur standards, but for us it really signifies what kind of mosasaur you're looking at," Konishi said. "If you have this protruding snout in this part of western Kansas, you're a Tylosaurus."

Like many other kinds of baby animals today, the baby mosasaur had not yet developed certain telltale features found in adults, Konishi said.

"The degree of snout development was nowhere near that of an adult, which made me look elsewhere such as the braincase to call it Tylosaurus in the end. It was the ugly duckling that hadn't yet become the graceful swan," Konishi said.

Unlike other mosasaur species, Konishi said the tylosaur had broader and more robust facial bones connected to a sturdy cranial vault that would have provided support as a battering ram.

Konishi pulled up a dramatic photo showing a breaching orca pummeling a large dolphin with its snout. The dolphin, a species called a false killer whale, was struck so hard that its body was contorted at a painful-looking angle.

"When orcas hunt dolphins and small whales, they subdue them by ramming them. And when you look at them, you see they have a protruding snout as well," Konishi said.

The fossils represent the youngest and smallest specimen of Tylosaurus ever found. Everhart confirmed to Konishi that the baby mosasaur was found alone with no associated fossils. Mosasaurs didn't lay eggs but gave birth to live young. That suggests the specimen was a free-swimming newborn rather than an embryo when it died, he said.

Just how the baby mosasaur perished is a matter of speculation. Only its skull was found. Konishi said the mosasaur could have succumbed to countless mishaps from predation to accident to disease.

It took a miracle of improbability that the baby mosasaur was found in the first place, he said.

Finding any baby dinosaur, or marine reptile in this case, is extremely rare for the simple reason that baby animals often end up as someone else's dinner. The bones of baby animals are lighter and more likely to scatter. But in this case, bones that weren't chewed up reached the ocean floor where they were covered in sediment and remained for millions of years until the seas receded and the former ocean floor became the wheat fields and farmlands of today's Kansas.

"And luckily an expert on mosasaurs was searching in exactly that spot and had sharp enough eyes to find it -- all separated by about 85 million years," Konishi said.

"Most fossils are fragmentary. You almost never find an entirely articulated fossil in the ground. That's near fantasy," Konishi said. "Luckily, the remaining bones were buried and became fossilized."

Konishi's theory strikes a chord with orca experts such as Ken Balcomb, senior scientist with the nonprofit Center for Whale Research outside Seattle, Washington. Balcomb has been studying orcas for 43 years. He has seen firsthand the myriad clever methods they employ to hunt different prey.

"They pummel their prey quite a bit. They will throw their body against a gray whale. They'll ram great white sharks, too," Balcomb said.

But Balcomb said they're choosy about what and how they attack, often using their flukes or whole body rather than their heads. They even distinguish between different types of prey.

"They know which kinds of seals will fight back," Balcomb said. "So they're cautious. They don't want to get hurt."

Contributing to Konishi's study were Paulina Jiménez-Huidobro and Michael Caldwell, both of the University of Alberta. The study was funded in part by the Natural Sciences and Engineering Research Council of Canada.

Konishi said this better understanding of the development of baby mosasaurs could help scientists learn more about fossils of other baby dinosaurs and marine reptiles that look markedly different from their parents.

"We now have a bit better insight into how this trademark feature evolved in this lineage," he said. "It's a good starting point for more studies in the future."

CLEVELAND--A common flesh fly takes off and maneuvers effortlessly, its head and body steadied by a hidden, miniscule gyroscope-like structure that gives it an unparalleled balance.

That same fly--those specialized structures, known as "halteres," now surgically removed--takes off again, but immediately begins to tumble wildly about, unable to right herself or tell up from down, side from side.

So what's happening? Why does it matter? And what might it mean for us?

Case Western Reserve University's Alexandra Yarger, a PhD candidate in biology and first author on a new paper published in September in the journal Proceedings of the Royal Society B, has some of the answers to those questions.

Yarger studies the electrical activity of neurons in the haltere structure, which was once a second set of wings, but transformed by millions of years of evolution into what serves as the unseen balancing system.

Her discoveries might someday help us build more responsive drones or better-balanced robots, said Jessica Fox, assistant professor of biology at Case Western Reserve and Yarger's mentor on the project. Her lab has been studying the behavior of flies and how sensory systems process information since 2013.

"We had already demonstrated in a 2015 paper what flies actually do with their halteres when moving around and in this paper, we've asked what their nervous systems do with that information," she said.

Advancing the long history of fly science

Yarger gained much of her insight by essentially taking over the operation of the haltere for several species of common flies: flesh flies, black flies and hoverflies. She glued a bit of metal to the tip of each fly's haltere and then manipulated it with a small magnet to simulate a change in orientation during flight and then recorded the electrical signals it generated--essentially a code sent "downstream" to the muscles make the fly a better flier than other insects.

"We know that the halteres activate the neurons, which in turn, tell their wings and neck what to do--but no one really knew exactly how that happened until now," said Yarger, who worked on the project over a period of about two years, beginning in 2016.

Scientists had first shown the effect of haltere removal as far back as 1714, Fox said.

And the idea that that when the fly was rotating, neurons might respond differently than when the fly was not rotating had been postulated 70 years ago by a scientist named J.W. Pringle, but he was never able to test his hypotheses directly for lack of technology to do the job.

But Pringle did have two related thoughts--that either some neurons that didn't fire when the fly was flying straight would start firing when the fly rotated; or that some neurons might change the timing of when they fire when the fly rotates, Fox said.

"Alex found that both of these ideas were correct and now we have a clear idea of what the code is because she found it," Fox said. "We found that this single spike moving around in time is what forms the code of 'I'm rotating' vs. 'I'm not rotating.'

"Next, we want to know how the downstream neurons integrate inputs from these 300 cells to produce an appropriate behavioral output."

Oct. 12, 2018--Long-term use of benzodiazepine medications in patients with chronic obstructive pulmonary disease, or COPD, as well as posttraumatic stress disorder (PTSD) may lead to increased suicide risk, according to a study published online in the Annals of the American Thoracic Society.

In "Risks of Benzodiazepines in Chronic Obstructive Pulmonary Disease with Comorbid Posttraumatic Stress Disorder," Lucas M. Donovan, MD, and coauthors report on a study of 44,555 veterans who received medical care between 2010-12. Of these, 23.6 percent received benzodiazepines long term (90 days or longer).

Benzodiazepines are commonly prescribed for COPD symptoms, including anxiety, shortness of breath and insomnia. They are also commonly prescribed to those with PTSD to treat anxiety and insomnia.

Their use for both patient groups is controversial because of adverse side effects, including an increased risk of COPD exacerbations and self-injury. Many guidelines specifically recommend against their use for patients with COPD or PTSD.

"The use of benzodiazepines among patients with high-risk comorbidities is a frequent dilemma for patients and clinicians," said Dr. Donovan, a pulmonary, critical care and sleep physician and health services researcher at the VA Puget Sound Healthcare System. "Understanding the risks of benzodiazepines is difficult because the symptoms that prompt their use, including anxiety and shortness of breath, are themselves linked with poor outcomes."

To better understand the risks posed by benzodiazepines, and not just the symptoms they treat, the researchers matched patients in their analysis by taking over 44 patient characteristics into account. These characteristics included medical and psychiatric history, medication use and health care utilization.
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The researchers found that long-term use of benzodiazepines in COPD patients who also had PTSD more than doubled their risk of suicide. These patients also had higher rates of psychiatric admissions.

Interestingly, the researchers did not find that long-term use of benzodiazepines in this patient group increased their risk of death from all causes or respiratory events, as previous studies have suggested.

The researchers did find that short-term use (less than 90 days) of benzodiazepines was associated with increased mortality, which supports previous findings. Dr. Donovan said this finding should be interpreted with some caution given the researchers did not use the same matching techniques employed in the primary analyses.

The authors said study limitations include the possibility of not being able to fully determine the severity of lung obstruction or PTSD from medical record data.

"Although long-term benzodiazepine use among patients with COPD and PTSD is not linked with overall mortality, the association with suicide is concerning," said Dr. Donovan, who is also an acting instructor at the University of Washington. "More research will be needed to better understand this link with suicide, but in the meantime we would advise that clinicians reconsider prescribing benzodiazepines to patients who already are at high risk for self-harm."

WASHINGTON, DC (Oct. 11, 2018) - A paper published today by researchers at the George Washington University Milken Institute School of Public Health (GW Milken Institute SPH) provides the data and methodology underlying an independent report that estimated there were 2,975 excess deaths in Puerto Rico during the six-month period after Hurricane Maria. The new study, which appears in The Lancet Planetary Health, also tracks the trends for mortality during that period. The study found that people living in all areas of Puerto Rico faced an elevated risk of mortality during the first two months after the storm, but this risk elevation was most prominent, and prolonged, for people living in the poorest parts of the island.

"This study offers public health officials a method to accurately size up the excess mortality due to natural disasters - not just in Puerto Rico but all over the world," said Carlos Santos-Burgoa, MD, MPH, PhD, a professor of global health at GW Milken Institute SPH and lead author of the study. "All jurisdictions should use total excess mortality as a practical, timely and sensitive way to monitor deaths after natural disasters. Public health officials can then step in with rapid interventions and influence the actions of other sectors in order to protect the most vulnerable populations."

The research was commissioned in February 2018 by the Government of Puerto Rico to provide an independent and accurate estimate of the number of people who had died after the category 4 hurricane. Unlike many post-disaster mortality studies, the researchers focused on all excess mortality related to the storm, not just deaths that were recorded as storm related on death certificates and in other official records. In addition to estimating the number of excess deaths after the hurricane, the investigation also evaluated the process of certifying deaths on the island and the Puerto Rican government's communication to the public before, during and after the storm.

A collaboration between researchers at GW Milken Institute SPH and the University of Puerto Rico Graduate School of Public Health, the study was based on official death certificates and other mortality data recorded from Sept. 1, 2017, through the end of February 2018. Using a state-of-the-art mathematical model that accounted for annual and seasonal variability, migration, sex, age and socioeconomic status of municipalities, the team compared the total number of deaths that were observed to occur during that time to the number that would have been expected to occur in a "normal" year.

This study is the only one of recent peer reviewed reports to factor in the island's population in estimating the number of excess deaths in Puerto Rico after the hurricane. This is important because a total of 241,251 people left the island from right before the storm hit on Sept. 20, 2017, through the end of February, about eight percent of the island's population. Such a large displacement in population must be considered in order to get an accurate mortality count, the authors say.

The paper describes the mathematical modeling and the rationale for selecting the most appropriate one. Using this model, the team estimated there were a total of 2,975 excess deaths (deaths above and beyond what could be expected in a normal year without a hurricane) from September 2017 through the end of February 2018. That number is still an estimate based on multiple factors but researchers say it is highly accurate, with a 95 percent confidence interval that ranges from a high of 3,290 to a low of 2,658.

The researchers found that 43 percent (1,271) of the total number of excess deaths were estimated to have occurred during the first two months (September and October) after the hurricane made landfall in the seaside municipality of Yabucoa, Puerto Rico. However, the excess deaths continued to be observed throughout the study period, with 347 excess deaths in November, 479 in December, 558 in January and 320 in February.

All areas of the island had elevated death rates in the first two months after the storm. However, for high and middle-income municipalities, the death rates fell back to the expected levels by November and December 2017 respectively.

In contrast, areas of the island with the lowest levels of socioeconomic development saw a continued excess rate of mortality through the end of the study's observation period. Over the entire period, the risk of dying was 22 percent higher than expected but was up to 60 percent for people living in the poorest municipalities of Puerto Rico.

Other higher risk groups that were identified by the study include the elderly and especially older male Puerto Ricans. They had a risk of death that was up to 35 percent higher than expected and their risk had not fallen back to baseline by the end of February 2018.

"These excess deaths are likely related to specific health consequences, such as injuries, worsening of chronic illnesses, or acute illnesses associated with the conditions in Puerto Rico during and after the storm," said Lynn R. Goldman, MD, MPH, Michael and Lori Milken Dean of the GW Milken Institute SPH and co-author of the paper. "Additional research must be done to find out how the hurricane was involved in the 2,975 excess deaths identified in this study."

Goldman went on to say that the GW Milken Institute SPH team hopes to conduct such a study, one that would interview family members to find out the circumstances leading up to each death.

"This study's results suggest that public health officials have underestimated mortality counts from past disasters in the United States and globally," added Santos-Burgoa. "At a time when hurricanes and other types of extreme weather are increasing in intensity, it is critical that all jurisdictions adopt total excess mortality as a practical, timely and sensitive indicator for impact assessment and monitoring."

Pediatric researchers have discovered common gene variants associated with migraines in African-American children. The research adds to knowledge of genetic influences on childhood migraine and may lead to future precision medicine treatments for African-American children with these intense headaches.

"Scientists already know that migraines may run in families, and other researchers have discovered multiple genetic links to migraine in European adults," said study leader Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at Children's Hospital of Philadelphia (CHOP). "However, this is the first large-scale genetic study of migraine in children and in African-Americans."

Hakonarson and colleagues published their study online on Sept. 28, 2018 in the Journal of Medical Genetics.

The researchers performed genome-wide association studies (GWAS) in separate groups of African-American (AA) and European-American (EA) children from CHOP's pediatric network. One study compared 380 AA children with migraine to 2,129 ancestry-matched control subjects. Another study compared 599 EA children with migraine to 7327 EA controls.

The scientists found a novel genetic susceptibility locus on chromosome 5, specifically 5q.33.1, that predisposed AA children to migraine, but was not significant for the EA children. The team then performed a replication study that confirmed this finding in an independent pediatric cohort of 233 AA migraine patients compared to 4038 AA control subjects without migraine.

Further analysis of the risk locus on chromosome 5 implicated two genes, NMUR2 and GLRA1, both involved in signaling pathways in the central nervous system. The researchers said this finding was consistent with previous GWAS research in adults that pointed to genes involved in neurotransmitter release.

"This work provides new insights into the genetic basis of childhood migraine," said Hakonarson. He added, "Our hope is that follow-up research on these signaling pathways may eventually lead to targeted migraine treatments for African-American children."

WEST LAFAYETTE, Ind. - Purdue University researchers are testing whether a light-active version of heme, the molecule responsible for transporting oxygen in blood circulation, may help people infected with MRSA.

MRSA led

Purdue University researchers are testing whether a simple light-emitting diode array that is safe to use on human skin can be used to inactivate methicillin-resistant Staphylococcus aureus, or MRSA, one of six 'high priority' pathogens that the World Health Organization has identified as an imminent threat to public health. Here the light shines above a 96-well plate in a bio-safety hood. (Purdue Research Foundation photo/John Underwood) Download image

The research was published in the American Chemical Society journal ACS Infectious Diseases in September. A link to the article is here.

The World Health Organization identifies MRSA as one of about a dozen antibiotic "superbugs" that pose an enormous threat to human health.

WHO has listed methicillin-resistant Staphylococcus aureus, or MRSA, as one of six 'high priority' pathogens with an imminent threat to public health. The Centers for Disease Control and Prevention reports 80,461 people in the United States suffer severe MRSA infections a year and 11,285 die.

Anyone can get MRSA on their body from contact with an infected wound, or by sharing personal items such as towels or razors that are contaminated. However, patients in hospitals are especially vulnerable to MRSA infections.

"MRSA infections can cause severe problems for patients recovering from surgery," said Alexander Wei, a professor of chemistry in the College of Science who is leading the research team. "The challenge that we face is that MRSA responds poorly to multiple antibiotics. Antimicrobial photodynamic therapy offers a promising alternative for combating MRSA in infected wounds."

Photodynamic therapy, or PDT, involves a compound known as a photosensitizer, which can be activated by visible light to kill diseased cells or bacteria. PDT is a clinically proven method for fighting cancer but has not yet been developed for treating MRSA infections.

The discovery aligns with Purdue's Giant Leaps celebration, recognizing the university's global advancements made in health, longevity and quality of life as part of Purdue's 150th anniversary. This is one of the four themes of the yearlong celebration's Ideas Festival, designed to showcase Purdue as an intellectual center solving real-world issues.

The photosensitizer developed at Purdue is called Ga-PpIX, and is an analog of heme. Ana Morales-de-Echegaray, the lead graduate research assistant on the project at the time, discovered that Ga-PpIX could be gobbled up by MRSA strains within seconds, leading to their rapid inactivation using a simple light-emitting diode (LED) array that is safe to use on human skin.

"Our discovery is part of a convergence on campus to develop drugs and get them to people in need as quickly as possible," Wei said.

Wei and his collaborator Mohamed Seleem, a professor in Purdue's College of Veterinary Medicine, are working closely with the Purdue Institute of Inflammation, Immunology and Infectious Disease and the Purdue Institute for Drug Discovery to determine if this kind of treatment could work for animals and with other types of skin infection.

The technology is patented through Purdue Office of Technology Commercialization, and the researchers are looking for partners to continue developing practical applications for the discovery.

Newark, N.J. (October 11, 2018) - Researchers have developed techniques to detect Lyme disease bacteria weeks sooner than current tests, allowing patients to start treatment earlier.

The findings appear in the journal Clinical Infectious Diseases. The authors include scientists from Rutgers Biomedical and Health Sciences, Harvard University, Yale University, the National Institute of Allergy and Infectious Diseases, FDA, Centers for Disease Control and Prevention, and other institutions.

The new techniques can detect an active infection with the Lyme bacteria faster than the three weeks it takes for the current indirect antibody-based tests, which have been a standard since 1994. Another advantage of the new tests is that a positive result in blood indicates the infection is active and should be treated immediately, allowing quicker treatment to prevent long-term health problems. The techniques detect DNA or protein from the Lyme disease bacteria Borrelia burgdorferi.

"These direct tests are needed because you can get Lyme disease more than once, features are often non-diagnostic and the current standard FDA-approved tests cannot distinguish an active, ongoing infection from a past cured one," said lead author Steven Schutzer, a physician-scientist at Rutgers New Jersey Medical School. "The problem is worsening because Lyme disease has increased in numbers to 300,000 per year in the United States and is spreading across the country and world."

Lyme disease signs frequently, but not always, include a red ring or bull's eye skin rash. When there is no rash, a reliable laboratory test is needed and preferably one that indicates active disease. The only FDA-approved Lyme disease tests rely on detecting antibodies that the body's immune system makes in response to the disease. Such a single antibody test is not an active disease indicator but rather only an exposure indicator -- past or present.

"The new tests that directly detect the Lyme agent's DNA are more exact and are not susceptible to the same false-positive results and uncertainties associated with current FDA-approved indirect tests," said Schutzer. "It will not be surprising to see direct tests for Lyme disease join the growing list of FDA-approved direct tests for other bacterial, fungal and viral infections that include Staphylococcus, Streptococcus, Candida, influenza, HIV, herpes and hepatitis, among others."

The authors developed the paper after a meeting at Cold Spring Harbor Laboratory's Banbury Conference Center, a nonprofit research institution in New York to discuss current Lyme disease tests and the potential of new scientific advances to increase the accuracy of an early diagnosis.

ABERDEEN PROVING GROUND, Md. (Oct. 11, 2018) -- An affordable children's educational kit is the latest commercial spinoff of research pursued by the U.S. Army to create advanced materials for Soldier systems.

A team of researchers funded by the Army created and designed a new resource for science teachers. BioBitTM is an educational platform for teaching synthetic biology to kindergartners through high school.

The team from the Massachusetts Institute of Technology, Harvard University and Northwestern University recently tested the platform in the Chicago Public Schools where students and teachers helped.

The test findings showed that students and teachers performed experiments successfully. The program fills a gap in current science, technology, math and engineering education, said Dr. Dawanne Poree, the Army's lead program manager on this project.

"The BioBitTM Explorer kit enables hands-on demonstrations of cutting-edge science that is inexpensive and easy to use, circumventing many current barriers for implementing exploratory biology experiments in classrooms," Poree said.

Chicago-area teachers partnered to develop curricula for high school math and middle school science classes, emphasizing the cross-cutting nature and the value of this activity at various educational levels, officials said.

The high cost and specialized equipment required for even the simplest demonstration of synthetic biology tools prevent many K-12 and some undergraduate schools from effectively teaching these methods, Poree said.

"If the United States is to continue leading research in synthetic biology in the coming decades, then current students must be encouraged to pursue long term study in this field," Poree said.

The kits are commercially available for an $100 to $200 for materials for a classroom of about 30 students.

BioBits is based on the latest methods in synthetic biology. They incorporates methods for freeze-drying harmless cellular extracts into pellets that can be packaged and distributed to classrooms.

These pellets provide individual experiments that can be activated in the classroom to reveal the power of synthetic biology through pre-designed reactions, said Dr. Michael Jewett, of Northwestern University. These pellets provide individual experiments that can be activated in the classroom to reveal the power of synthetic biology through pre-designed reactions.

This platform grew out of prior and ongoing research funded by the Army Research Laboratory's Army Research Office to develop new tools in synthetic biology with the goal of adapting cellular machinery to produce non-biological materials.

Specifically, researchers were initially exploring the mechanisms of protein synthesis inside cells with the long term goal of harnessing and adapting cellular machinery to produce non-biological materials. This research involves the development of new methods in synthetic biology that will be required to utilize powerful biological enzymes to create polymers of interest for the Army.

Research in synthetic biology will be essential for realizing scientific discoveries in the 21st century such as responsive materials, game-changing chemical, material, and drug manufacturing methods, the detection and elimination of toxic chemicals, and medical applications ranging from the detection and treatment of traumatic brain injury to the development of integrated prosthetics.

Fueled by political rhetoric evoking dangerous criminal immigrants, many white Americans assume low-status immigrants from Mexico, El Salvador, Syria, Somalia and other countries President Donald Trump labeled "shithole" nations have no legal right to be in the United States, new research in the journal American Sociological Review suggests.

In the eyes of many white Americans, just knowing an immigrant's national origin is enough to believe they are probably undocumented, said Ariela Schachter, study co-author and assistant professor of sociology in Arts & Sciences at Washington University in St. Louis.

"Our study demonstrates that the white American public has these shared, often factually incorrect, stereotypes about who undocumented immigrants are," Schachter said. "And this is dangerous because individuals who fit this 'profile' likely face additional poor treatment and discrimination because of suspicions of their illegality, regardless of their actual documentation."

Findings suggest that the mere perception of illegal status may be enough to place legal immigrants, and even U.S. citizens, at greater risk for discrimination in housing and hiring, for criminal profiling and arrest by law enforcement, and for public harassment and hate crimes in the communities they now call home.

"When people form impressions about who they think is 'illegal,' they often do not have access to individuals' actual documents. There have actually been a number of recent incidents in which legal immigrants and even U.S. born Americans are confronted by immigration authorities about their status. So these judgments seem to be based on social stereotypes. Our goal was to systematically uncover them," said study co-author René D. Flores, the Neubauer Family Assistant Professor of Sociology at the University of Chicago.

From a broader sociological perspective, Schachter and Flores argue that an immigrant's real standing in American society is shaped not just by legal documentation, but also by social perceptions.

"These findings reveal a new source of ethnic-based inequalities -- 'social illegality' -- that may potentially increase law enforcement scrutiny and influence the decisions of hiring managers, landlords, teachers and other members of the public," they conclude in the research.

Conducted in November 2017, the experimental survey asked a representative sample of 1,500 non-Hispanic white Americans to guess whether a hypothetical immigrant was in the country illegally -- and perhaps a threat worth reporting to authorities -- based on the reading of a brief biographical sketch.

By systematically varying the immigrant's nation of origin, education level, language skills, police record, gender, age, race and other variables, researchers created a pool of nearly 7 million unique immigrant sketches that touched on a range of stereotypes. Each respondent was randomly assigned to view 10 of these unique sketches during the survey.

Using complex statistical analysis, researchers estimated how much each of these individual immigrant traits and stereotypes influenced the assumptions of white Americans from various demographic backgrounds, geographic regions and self-identified political affiliations.

Surprisingly, the study found that white Republicans and white Democrats jump to many of the same conclusions about the legal status of hypothetical immigrants -- except when it comes to the receipt of government benefits.

Democrats rightfully recognize that in order to receive government benefits, immigrants must have legal documentation, whereas Republicans are more likely to suspect that receiving benefits marks an immigrant as illegal, even though by law undocumented immigrants are blocked from receiving federal benefits such as welfare.

Most tellingly, even the slightest hint of an immigrant with a criminal background has a huge effect on whether a white American suspects that the immigrant is in the country illegally.

"Saying an immigrant committed a crime had a larger impact on suspicions of illegality than saying they were, say, Mexican," Schachter said. "This is true for both white Democrats and white Republicans. There's a clear implication that the Trump administration's rhetoric on immigrant criminality is driving these beliefs, which, again, are not based in reality. In fact, other research finds that undocumented immigrants are less likely to commit crimes than native-born Americans."

The study also demonstrates significant differences in how immigrants from various countries and differing social statuses are likely to be treated in the United States.