Culture

Researchers at the University of Cincinnati found that Charles Darwin's famous finches defy what has long been considered a key to evolutionary success: genetic diversity.

The study of the finches of the Galapagos Islands could change the way conservation biologists think about species with naturally fragmented populations to understand their potential for extinction. 

UC graduate Heather Farrington and UC biologists Kenneth Petren and Lucinda Lawson found that genetic diversity was not a good predictor of whether populations of finches would survive. A UC lab analysis of century-old museum specimens found that six of eight extinct populations had more genetic diversity than similar museum specimens from which descendants survive today. In most other species, low genetic diversity is a signal of a population in decline.

Researchers examined 212 tissue samples from museum specimens and living birds. Some of the museum specimens in the study were collected by Darwin himself in 1835. Only one of the extinct populations, a species called the vegetarian finch, had lower genetic diversity compared to modern survivors.

Lawson said the findings are explained by the fact that these birds can migrate in between populations.

Specifically, researchers believe a biological phenomenon called sink-source dynamics is at play in which larger populations of birds from other islands act as a "source" of immigrants to the island population that is naturally shrinking, the "sink." Without these immigrant individuals, the natural population on the island likely would continue to dwindle to local extinction. The immigrants have diverse genetics because they are coming from a variety of healthier islands, giving this struggling "sink" population inflated genetic diversity.

Petren said the findings serve as a warning that the genetics of individuals in fragmented populations might not tell the whole story about a species. And that is important for scientists who increasingly use genetics to account for the flow of genes between populations when determining a threatened species' likelihood of extinction.

"The promise of genetics is to sample a few individuals to understand the whole population. But it's a cautionary note that you might be sampling a fragment. You could be misled," he said.

Petren has been studying the birds for 25 years at UC's McMicken College of Arts and Sciences. He said the island's 18 recognized species of finches are unusual for other reasons. Some finches that look most different are actually closely related, he said. And similar-looking finches that birders might have trouble telling apart are actually far apart on the evolutionary family tree.

"It's a paradox. If Darwin fully understood what was going on, it might have blown his mind," Petren said. "These finches are not the first case you would pick to formulate the notion that species can change over time because the patterns of change are so complicated."

The UC study was published in August in the journal Conservation Genetics after first appearing online in April. It suggests that genetic diversity may not be the best predictor of extinction risk for mobile species like the island-hopping finches. That’s because healthier populations may contribute individuals to declining ones.  

Lawson said factors such as historical diversity or the possibility of gene flow between populations should be considered in addition to the snapshot view provided by a genetic analysis for a fuller understanding of a species' potential for extinction.

"Typically, we would expect populations with high genetic diversity to have a greater potential for long-term survival," she said. "Meanwhile, the low-diversity populations would be more likely to go extinct because that's a common pattern as populations decline to few individuals. Surprisingly, we found that most of the extinct populations had higher genetic diversity."

The study was sponsored in part by the National Science Foundation, Sigma Xi, the American Ornithologists' Union and UC's Office of Research.

Darwin's "On the Origin of Species" was groundbreaking in our understanding of evolution through natural selection. "Survival of the fittest" is a household phrase and a shorthand description of any competition.

While scientists today know more about how new species are formed, the principles Darwin developed remain the foundation of evolutionary biology, Petren said.

"Certainly, genetics is new. But the fundamental principles still stand. It's amazing how much of his work remains fundamentally true today," Petren said.

The function of the visual photopigment rhodopsin and its action in the retina to facilitate vision is well understood. However, there remain questions about other biological functions of this family of proteins (opsins) and this has ramifications for our understanding of several evolutionary pathways. Now, an international research team led by the University of Göttingen has shown there are other functions of opsin outside vision and this provides insights into how the eye evolved. Their research was published in Current Biology.

Vision relies on rhodopsins, which are made from proteins (opsins) that bind with "retinal" (a small molecule derived from vitamin A). This molecule changes its structure when stimulated by light and enables us to see: without retinal, photoreceptor cells die and there is no vision. Intriguingly, in the fruit fly Drosophila, the same opsin proteins that enable vision also occur in the ear. Researchers from the Department of Cellular Neurobiology and the Institute of Molecular and Cellular Physics of the University of Göttingen therefore asked if these auditory receptors were light-sensitive, i.e. could the ears of this fly also sense light? The researchers quickly discovered that the fly's ear could not function as an eye. What the researchers deduced, however, is a completely new function of opsins independent from the molecule retinal and from the functioning of the eye. They tested this by making vitamin A unavailable to Drosophila through various experiments: taking vitamin A out of the fly's diet; disrupting the transport protein that mediates vitamin A uptake into gut cells; and blocking the enzyme that converts vitamin A into retinal. This rendered the insects blind - but they did not become deaf. Together with colleagues in the US, the researchers then manipulated the opsins so that they could no longer bind with retinal. As expected, this made the flies blind, but again their hearing remained intact. This showed that the fruit fly requires opsins (but not retinal) for hearing, adding a new twist to the function of photopigment proteins. The real surprise came when the scientists looked at those enzymes that, in the eye, recycle light-activated retinal back into its light-sensitive form. All those enzymes turned out to occur in the fly's ear as well as the eye and were essential for hearing, even though hearing works without retinal. Hence, not only opsins, but also all the retinal-enzymes, have other important biological functions that are independent of vision.

"From an evolutionary perspective, this is quite striking," explains Dr Radoslaw Katana, the first author of the study. "The receptor cells for vision and hearing are derived from common ancestor cells, which seem to have used opsins and retinal-enzymes even before vision and hearing were possible. This is also the case in vertebrates: opsins occur in mechanoreceptor cells and many of the retinal-enzymes have remained essentially unchanged throughout evolution and are also implicated in human hearing".

"The retinal cycle in the eye is the most thoroughly studied biological signalling cascade," remarks Professor Martin Göpfert. "It now seems that its molecular components originally had nothing to do with the eye or light, revolutionising our understanding of the early evolution of vision".

LA JOLLA--(August 22, 2019) Light touch plays a critical role in everyday tasks, such as picking up a glass or playing a musical instrument. The sensation is also an essential part of the body's protective defense system, alerting us to objects in our environment that could cause us to fall or injure ourselves. In addition, it is part of the detection system that has evolved to protect us from biting insects, such as those that cause malaria and Lyme disease, by eliciting a feeling of an itch when an insect lands on your skin.

Salk researchers have discovered how neurons in the spinal cord help transmit such itch signals to the brain. Published in the journal Cell Reports on July 16, 2019, their findings help contribute to a better understanding of itch and could lead to new drugs to treat chronic itch, which occurs in such conditions as eczema, diabetes and even some cancers.

"The takeaway is that this mechanical itch sensation is distinct from other forms of touch and it has this specialized pathway within the spinal cord," says Salk Professor Martyn Goulding, holder of the Frederick W. and Joanna J. Mitchell Chair and a senior author of the new work.

Goulding and his colleagues had previously discovered a set of inhibitory neurons in the spinal cord that act like cellular brakes, keeping the mechanical itch pathway in the spinal cord turned off most of the time. Without these neurons, which produce the neurotransmitter neuropeptide Y (NPY), the mechanical itch pathway is constantly on, causing chronic itch. What the researchers didn't know was how the itch signal, which under normal circumstances is suppressed by the NPY neurons, is transmitted to the brain to register the itch sensation.

David Acton, a postdoctoral fellow in the Goulding lab, hypothesized that when the NPY inhibitory neurons are missing, neurons in the spinal cord that normally transmit light touch begin to act like an accelerator stuck in the "on" position. Acton then identified a candidate for these "light touch neurons," a population of excitatory neurons in the spinal cord that express the receptor for NPY, the so-called Y1 spinal neurons.

To test whether these neurons were indeed acting like an accelerator, Acton undertook an experiment that involved selectively getting rid of both the NPY "brake" and Y1 "accelerator" neurons. Without Y1 neurons, mice didn't scratch, even in response to light-touch stimuli that normally make them scratch. Moreover, when Acton gave the animals drugs that activated the Y1 neurons, the mice scratched spontaneously even in the absence of any touch stimuli. The Goulding team was then able to show that the NPY neurotransmitter controls the level of Y1 neuron excitability; in other words, NPY signaling acts as a kind of thermostat to control our sensitivity to light touch. Data from other labs has found that some people with psoriasis have lower than average levels of NPY. This may mean their brakes on mechanical itching are less effective than other people's, a potential cause of their itching.

While Y1 neurons transmit the itch signal in the spinal cord, other neurons are thought to be responsible for mediating the final response in the brain but more research is needed to continue mapping out the full pathway, according to the researchers. Understanding this will help suggest targets for drugs to turn down the sensation of itch in people who are overly responsive and could lead to ways to address chronic itch.

"By working out mechanisms by which mechanical itch is signaled under normal circumstances, we might then be able to address what happens in chronic itch," says Acton.

In a pioneer study now published in Proceedings of the National Academy of Science - USA, led by Isabel Gordo research team, from the Instituto Gulbenkian de Ciencia (IGC) (Portugal), in collaboration with researcher Michael Lässig of Cologne University (Germany), used healthy mice to study real-time gut colonization and discovered a pivotal role for bacterial sex in the evolution of the mammalian microbiome. This discovery constitutes a paradigm shift and opens the possibility to design phage-targeted therapies capable of dealing with the aftermath of infection and antibiotic usage, as well as antibiotic-resistant bacteria.

Most of what we know about bacterial colonization of the gut comes from studies with pathogenic bacteria in highly artificial laboratory models or disease contexts. Standard experimental models, which focus on infections with pathogenic bacteria and continuous antibiotic treatment, have not detected phage-driven horizontal gene transfer (HGT) and suggest that bacteria colonizing the gut evolve mainly through accumulation of mutations. In a surprising finding, the work of the IGC researchers now shows that HGT, not mutations, is the first evolutionary mechanism driving the pace and outcome of bacterial evolution in a healthy gut.

Escherichia coli is a common colonizer of the human intestine as well as a potential pathogen. The colonization outcome is greatly influenced by different speeds and modes of evolution of this opportunistic bacterium. E. coli can evolve through mutations, which are then inherited by daughter cells, or through a process of recombination, i.e. bacterial sex, in which genetic material is shared between unrelated individuals. In the mouse and human intestine, this transfer of genetic material involves temperate bacteriophages (phages), viruses that infect bacteria and integrate into the bacterial chromosome as prophages, a process called lysogeny. Prophages can later extricate themselves (and their genetic information) from the bacterial DNA and infect other bacteria in the gut microbiome.

Nelson Frazão, a post-doctoral researcher in Isabel Gordo´s lab and junior author of the study, says: "phages often classified as selfish particles reveal their altruistic side in the gut, providing a metabolic advantage to their bacterial host to conquer and colonize the gut". The phage genetic material that is transferred enables bacteria to gain access to specific carbon sources present in the gut, which provides a fitness advantage to phage-carrying (lysogenic) invader bacteria.

"We found that the classical evolution model does not apply, and in fact horizontal gene transfer greatly overrides the contribution of evolution through accumulation of mutations in the intestine of a healthy mouse", says the investigator Isabel Gordo. "With this work, we now understand better how evolution works in normal, healthy hosts", says Nelson Frazão, junior author of the publication.

CHAPEL HILL, N.C. - August 22, 2019 - E-cigarette "vaping" is widely assumed to be safer than cigarette smoking, but scientists at the University of North Carolina School of Medicine have uncovered evidence suggesting that vaping promotes the same cellular responses found in smokers who suffer with emphysema.

In a study published in the American Journal of Respiratory and Critical Care Medicine, the UNC scientists found that the lungs of vapers - like the lungs of smokers - have elevated levels of protease enzymes, a condition known to cause emphysema in smokers. The researchers also found that the nicotine in vaping liquids is responsible for the increase in protease enzymes.

"Our findings in this study indicate that vaping may not be safer than cigarette smoking," said study senior author Robert Tarran, PhD, a professor in the department of cell biology and physiology and member of the Marsico Lung Institute at the UNC School of Medicine.

The U.S. Centers for Disease Control and Prevention (CDC) has estimated that in 2014 about 9 million adults in the country were regular vapers and that close to 30 million had tried vaping at least once. But vaping on this scale has been going on for less than a decade, and so the long-term health effects of vaping are not yet well understood.

Tarran and colleagues in the study measured levels of three key protease enzymes in lung fluid sampled from 41 subjects - nonsmokers, smokers, and vapers. The three protease enzymes are neutrophil elastase and matrix metalloproteases 2 and 9. Immune cells in the lungs are known to secrete these enzymes at higher levels in a reaction to cigarette smoke. Chronic over activity of these protein-chewing enzymes damages the tiny sensitive air sac structures in the lungs that allow people to breathe. In smokers, this damage is thought to be the cause of emphysema, a form of chronic obstructive pulmonary disease (COPD) involving progressive shortness of breath and for which there is no cure.

The UNC scientists found that the levels of these three proteases were significantly elevated in both smokers and vapers, but not in nonsmokers. This finding suggests vaping, like smoking, may promote emphysema.

The scientists also found evidence that nicotine in vaping liquids is the cause of the elevated-protease reaction. When Tarran's team administered nicotine to immune cells cultured in the laboratory - at concentrations like those seen in vapers sputum and lung fluid - they observed that the cells overproduced the proteases. And this overproduction increased when the researchers exposed the immune cells to higher nicotine levels.

Vaping is thought to be much safer than cigarette smoking, which involves the high-temperature burning of tobacco leaves and the creation of toxic and carcinogenic combustion products. Some researchers have urged that smokers switch to vaping as a much less harmful alternative. The jury is still very much out when it comes to cancer risk associated with vaping. But this latest study suggests that the potential harm of vaping may have been underestimated, especially when it comes to emphysema and COPD, two of the most common debilitating conditions historically associated with smoking.

Tarran noted that the findings are not the first to warn of vaping's potential adverse health effects. A different study in 2018, from a team led by UNC Marsico Lung Institute researcher Mehmet Kesimer, PhD, found that sputum from vapers and smokers contained elevated levels of emphysema-promoting proteases and other immune defense proteins.

Moreover, a study from Tarran's lab last year found evidence of toxic compounds in commonly used vaping liquids, and the CDC currently is investigating about 100 recent cases in the U.S. of sudden, serious lung disease in otherwise healthy young vapers.

Tarran and his colleagues plan to follow up their new study with a larger study of lung protease levels in hundreds of participants.

Microbiomes aren't just for understanding and modulating gut health - skin, our largest organ, hosts a vibrant and complex microbiome that can provide health insights. An international research team has developed an index to better understand skin health across human populations.

They published their results on August 20 in mSystems, a journal issued by the American Society for Microbiology.

"A central goal of human microbiome projects is to diagnose and predict the human's healthy or unhealthy state via the microbiome," said XU Jian, senior author and director of the Single-Cell Center and Shandong Key Laboratory of Energy Genetics at the Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS).

In guts, the composition of microbes present can indicate health and diet issues. In skin, it can operate the same way. XU noted that by understanding the skin microbiome, researchers can also predict how the skin may react to specific treatments.

The issue, though, is that skin microbiome differs between human populations due to environment, health status, body locations, diet and other mitigating factors.

"Due to the variance, the ability to use skin microbiome as an indicator of skin health that applies across large geographic ranges has remained largely unexplored," XU said. "As such, the central question of this study is: can we harness the talent and power of our skin microbiome for precise skin care, such as diagnosis and treatment?"

To answer this question, the international team which consists of CAS, Procter & Gamble, UCLA and UCSD assessed children with healthy skin and those with Atopic Dermatitis (eczema), the irritating skin condition that causes the skin to turn red and itch. Eczema affects 15 to 30 percent of children around the globe, so the researchers examined children in three different cities: Beijing and Qingdao in China and Denver, Colorado in the United States. Qingdao is a coastal city approximately seven hours drive north of Beijing. Denver is a mountain city, with a higher elevation than the other two cities.

In these vastly different locations, the researchers identified 25 bacterial genera - the taxonomic ranking above species - in the skin microbiomes of children and developed a Microbial index of Skin Health (MiSH).

According to SUN Zheng, the first author of the paper, this index can identify skin conditions, such as eczema, and has implications in clinical settings. Currently, eczema is identified via a scaling system where a physician observes a patient with multiple symptoms than add up to eczema. MiSH identifies it with an 83 to 95 percent accuracy within each city and with 86.4 percent accuracy across all cities.

"MiSH can quantitatively assess pediatric skin health across cohorts from distinct countries over large geographic distances," SUN said, explaining that index serves to compare skin health via the microbes that live on the skin. "MiSH can identify a risk-prone skin state and predict treatment effect in children, suggesting applications in patient stratification and personalized treatment in the clinics and in the skin care industry."

Next, the researchers plan to further study the mechanisms by which the index helps predict skin health and refine how well it predicts treatment response in larger and wider cohorts.

Used as a propaganda tool by the Nazis and Soviets during the Second World War and Cold War, the remains of a 10th century male, unearthed beneath Prague Castle in 1928, have been the subject of continued debate and archaeological manipulation.

The mysterious skeleton and associated grave goods, including a sword and two knives, were identified as Viking by the Nazis, as a Slavonic warrior by the Soviets and became part of the Czech independence movement in more recent years.

Writing in the journal Antiquity, a team of archaeologists, including two emeritus professors from the University of Bristol, unravel the complex story of the discovery of the remains, which were kept out of public view until 2004, and attempt to answer the decades-long question of who this man actually was.

The remains were discovered under the courtyard of Prague Castle in July 1928 as part of an excavation project by the National Museum of the newly established Czechoslovakia to discover the earliest phases of the castle.

The body was located on the edge of an old burial ground from when a hill fort was built on the site, likely dating to AD 800-950/1000.

It was discovered by Ivan Borkovský, a Ukrainian who fought for both the Austro-Hungarians and the Russians in the early 20th century, before escaping to Czechoslovakia in 1920 but he did not immediately publicise or publish anything about the remains or the artefacts.

In 1939, the German army invaded Czechoslovakia and immediately accused Borkovský of not publishing because he was part of a Czech conspiracy to hide the truth¬--that the remains were German, rather than Slavic (or maybe Viking).

As a German ancestor, the remains supported the German propagandist efforts to argue for a German heritage that 'extended over national borders and reached deep into the past'.

Under the Nazi regime, the remains became 'proof' for the Germanic, rather than Slavic, origin of Prague Castle.

When Borkovský published a book identifying the oldest Slavic pottery in central Europe, the Nazi's condemned the text and he was forced to withdraw it under threat of imprisonment in a concentration camp. When he published the Prague Castle remains a year later, it was overt in its 'Nazi-influenced Nordic interpretation'.

After the war, Czechoslovakia was occupied by the Soviets and in 1945, Borkovský narrowly escaped being sent to a Siberian Gulag because of former anti-Communist activities.

He explained that he had been forced into the pro-Nazi interpretation of the remains and published a second article in 1946 which interpreted the burial 'as that of an important person who was related to the early Western Slav Przemyslid dynasty'.

Lead author Professor Nicholas Saunders, from Bristol's Department of Anthropology and Archaeology, said: "A number of studies have recently begun to re-interpret the remains and ours provides a new analysis.

"The goods found with the remains are a mix of foreign (non-Czech) items, such as the sword, axe and fire striker (a common piece of Viking equipment), and domestic objects, such as the bucket and the knives.

"The sword is especially unique as it is the only one discovered in 1,500 early medieval graves so far found in Prague Castle.

"Perhaps he was a Slav from a neighbouring region, who had mastered Old Norse as well as Slavonic, or perhaps he regarded himself as a genuine Viking.

"Identities were complex in the medieval period, and the story of Borkovský and the Prague Castle warrior grave reminds us that the identities of such past people frequently fuel modern political conflicts."

DALLAS, Aug. 22, 2019 -- High-intensity step training that mimics real-world conditions may better improve walking ability in stroke survivors compared to traditional, low-impact training, according to new research published in the American Heart Association's journal Stroke.

"People who suffer strokes often have difficulty walking and impaired balance. Rehabilitation after a stroke traditionally focuses on patients practicing low-intensity walking, usually only in a forward direction, which does not provide enough of a challenge to the nervous system to enable patients to negotiate real-world situations, such as uneven surfaces, stairs or changing direction," said study author T. George Hornby, Ph.D., professor of physical medicine and rehabilitation at Indiana University School of Medicine in Indianapolis. "Our study suggests that stroke patients can perform higher intensity walking exercises and more difficult tasks than previously thought possible. We need to move beyond traditional, low-intensity rehabilitation to challenge the nervous and cardiovascular systems so patients can improve function and perform better in the real world."

Researchers evaluated 90 people, 18- to 85-years-old with weakness on one side of the body who had survived a stroke at least six months prior.

Participants received training of either high-intensity stepping performing variable, difficult tasks; high-intensity stepping performing only forward walking; or low-intensity stepping of variable tasks. Variable tasks included walking on uneven surfaces, up inclines and stairs, over randomly placed obstacles on a treadmill and across a balance beam.

The researchers found:

Survivors in both the high-intensity, variable training and high-intensity, forward walking groups walked faster and farther than the low-intensity, variable training group.

For all walking outcomes, 57% to 80% of participants in the high-intensity groups had important clinical gains, while only 9% to 31% of participants did so following low-intensity training.

High-intensity variable training also resulted in improved dynamic balance while walking and improved balance confidence.

Hornby noted that no serious adverse events occurred during the training sessions, suggesting stroke survivors can be pushed to higher intensity walking with more variable tasks during rehabilitation.

"Rehabilitation that allows walking practice without challenging the nervous system doesn't do enough to make a statistical or clinically significant difference in a patient's recovery after a stroke," Hornby said. "We found that when stroke patients are pushed harder, they see greater changes in less time, which translates into more efficient rehabilitation services and improved mobility."

Ultimately, their goal is to incorporate high-intensity variable step training into regular clinical rehabilitation protocols.

The study was small compared to larger, multicenter clinical trials. Hornby said the next step would be to test high-intensity, variable step training in larger patient populations in a large, multicenter clinical trial.

Philadelphia, August 22, 2019 - Patient-reported experiences have potential for driving improvements in the quality of hospital care, according to a new study in the Canadian Journal of Cardiology, published by Elsevier. Investigators report on an analysis of the Canadian Patient Experience Survey responses obtained from cardiac patients in Alberta, which revealed areas that are highly rated by patients, but also reported findings around areas that could be the subject of future patient-centered quality improvements.

The term "patient-centered care" is gaining currency as it places the patient first, rather than reducing them to the sum of their symptoms or medical condition. Providing patients' first-hand reports of their care is important to help reinforce or confirm areas in which care is working well (from the patient perspective), as well as to guide quality improvement experts to where impactful improvements can be made. Patient-centered care is often measured through surveys, specifically those that measure the patient experience. Despite the proliferation of such surveys, there is limited research in this area.

Using records from the Canadian Patient Experiences Survey - Inpatient Care (CPES-IC), investigators analyzed the experiences of over 1,000 patients in Alberta who underwent coronary artery bypass graft (CABG) and/or valve replacement from April 2014 to March 2018.

"To our knowledge, this is the first study of its kind in Canada - one that uses linkage of patient experience surveys with routinely-collected administrative data to examine the comprehensive hospital experience of a particular clinical group," explained lead investigator Kyle A. Kemp, a PhD candidate working in the Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. "Examining the comprehensive experience of patients who have undergone cardiac procedures such as CABG and valve replacement may provide tremendous value, given the labor-intensive and costly nature of these procedures."

CPES-IC surveys are administered across 93 hospitals in Alberta using a standard script and responses to frequently asked questions. A random sample of 10 percent of eligible discharges is obtained from each hospital, resulting in approximately 25,000 completed surveys each year. Participants complete a 56-question telephone survey after being discharged from hospital. Questions assess many aspects of care, including communication with doctors and nurses, medications, patient/family involvement in care, pain control, the physical environment, coordination of care, and discharge planning.

The results were rated on a scale from 0 (worst) to 10 (best) and overall were quite positive. More than 73 percent of the 1,082 respondents rated their overall hospital care as a 9 or 10. Top performing questions pertained to discussing help needed after discharge (96.6 percent responding "yes") and receiving written discharge information (93.2 percent responding "yes"). The responses also identified areas that could be targeted in quality improvement efforts. For example, less than 40 percent of respondents reported that the space around their room was always quiet at night, and only about 45 percent reported that hospital staff had always described the potential side effects of any new medications that patients were given.

"These findings are important because historically, many efforts to improve hospital care have been driven by administrators or clinicians - largely in absence of the 'patient voice'," commented Mr. Kemp. "Being the first Canadian study of its kind, there is an opportunity for it to serve as a baseline when examining future data from this survey, both in Alberta and from other Canadian provinces. The study methodology can be also replicated elsewhere in Canada and throughout the world to examine the experience of other clinical populations such as joint replacement patients, labor and delivery patients, and seniors living with chronic diseases."

"The study by Kemp and colleagues is a step in the right direction and is in essence the first rung on the ladder towards meeting the much sought-after triple aim (better health, improved experiences of care, and lower costs for the system) of healthcare in Canada," commented Michelle M. Graham, MD, and Colleen M. Norris, PhD, GNP, both from the University of Alberta and the Mazankowski Alberta Heart Institute, Edmonton, AB, Canada, in an accompanying editorial. "The investigators have in fact provided a methodology for building a Pan-Canadian patient-centered database required to drive improvement in various demographic, regional, and clinical cohorts in the Canadian health care system. Patients have been given a new way to speak; we just have to listen. Providing truly relevant, patient-centered care is dependent on it."

Neurons communicate with each other by sending out rapid pulses of electrical signals called spikes. At first glance, the generation of these spikes can be very reliable: when an isolated neuron is repeatedly given exactly the same electrical input, we find the same pattern of spikes. Why, then, does the activity of cortical neurons in a live animal fluctuate and actually seem so variable?

There are two reasons for this. Firstly, when transmitting a signal to another neuron, the process can sometimes fail and these failures are unpredictable - like rolling a die to decide on an outcome. "We estimate the chance of a synapse between two cortical pyramidal neurons passing a chemical neurotransmitter signal can be as low as 10%," explains lead researcher Max Nolte. This uncertainty means that a neuron will hear the same message sent by connected neurons differently every time.

Secondly, when the two fundamental types of cortical neurons (excitatory and inhibitory) are interconnected in a network, small uncertainties in activity patterns become amplified. This leads to unpredictable patterns, a behavior that is called chaos.

This backdrop of noise and chaos suggests that individual cortical neurons cannot find order and fire reliable spikes, and so the brain has to 'average' the activity of many neurons for certainty - listen to the whole choir instead of individual singers.

Simulation neuroscience finds the answer

The experimental manipulations required to untangle the noise sources in the brain and evaluate their impact on neuronal activity are currently impossible to perform in a live animal in vivo, or even in separated brain tissue in vitro. "For the moment, it is simply not possible to monitor all of the thousands of brain-wide inputs to a neuron in vivo, nor to turn on and off different noise sources," says Nolte. The closest approximation of cortical tissue to date in a model is the Blue Brain Project's biologically detailed digital reconstruction of rat neocortical microcircuitry (Cell 2015). This computer model provided the ideal platform for the researchers to study to what degree the voices of individual neurons can be understood, as it contains data-constrained models of the unreliable signal transmission between neurons.

Using this model, they found that activity that is spontaneously generated from the interconnected neurons is highly noisy and chaotic, depicting very different spike times in each repetition. "We studied the origin and nature of cortical internal variability with a biophysical neocortical microcircuit model with biologically realistic noise sources," reveals Nolte. "We observed that the unreliable neurotransmitter signals are amplified by recurrent network dynamics, causing a rapidly decaying memory of the past - a sea of noise and chaos."

Reliable responses amidst noise and chaos

But, of course the mammalian brain does not have a rapidly decaying memory. In fact, perhaps the most fascinating insight from the findings is that spike times that were highly unreliable during spontaneous activity became highly reliable when the circuit received external inputs. This phenomenon was not simply a result of strong external input directly driving the neurons to reliable responses. Even weak thalamocortical input could switch the network briefly to a regime of highly reliable spiking. At that point, the interactions between the neurons that otherwise amplify uncertainty and chaos conversely amplify reliability and allow the brain to find order.

"Thalamocortical stimuli can prompt reliable spike times with millisecond precision amid noise and chaos," explains Blue Brain Founder and Director, Prof. Henry Markram. "Surprisingly, we were able to demonstrate that this effect relies on the cortical neurons working as a team. Our model thus shows that noise and chaos in networks of cortical neurons are compatible with reliable spiking, allowing the brain to find order. This finding suggests that the highly fluctuating activity of cortical neurons in a live animal is reflecting order, not noise and chaos," Markram concludes.

34 million years ago the warm ‘greenhouse climate’ of the dinosaur age ended and the colder ‘icehouse climate’ of today commenced. Antarctica glaciated first and geological data imply that the Atlantic meridional overturning circulation, the global ocean conveyor belt of heat and nutrients that today helps keep Europe warm, also started at this time. Why exactly, has remained a mystery.

"We have found a new trigger to explain the start-up of the Atlantic current system during the greenhouse-icehouse climate transition: During the warm climate, buoyant fresh water flooded out of the Arctic and prevented the ocean-sinking that helps power the conveyor. We found that the Arctic-Atlantic gateway closed due to tectonic forces, causing a dramatic increase in North Atlantic salinity. This caused warming of the North Atlantic and Europe, and kickstarted the modern circulation that keeps Europe warm today," says David Hutchinson, researcher at the Department of Geological Sciences, Stockholm University, and lead author of the article published in Nature Communications.

The team of scientists, from the Bolin Centre for Climate Research, used a combination of geophysical data and climate modelling to show that the freshwater transport through the Arctic-Atlantic gateway plays a critical role in controlling the overturning circulation.

"Not only did deep water start forming in the Atlantic Ocean, it also stopped forming in the North Pacific at the same time, which matches geological evidence. We were surprised to find that our computer simulations can explain both of these changes due to salty ocean currents connecting the Pacific to the Atlantic. Our study is the first to show that these two events are linked, which is very exciting," says Hutchinson.

The climate at this time was very warm, with atmospheric CO2 levels two to three times the present day levels, and this contributed to extremely fresh Arctic waters. The study begs the question of whether in a future warm world, in which the Arctic may again be very fresh, the sinking in the Atlantic may cease again, which may dramatically alter the climate of Europe. Without the Atlantic conveyor belt, Europe can experience both colder winters and hotter and drier summers, making a more extreme and inhospitable climate.

"Our study helps to bridge the gap between climate modelling and geological observations of the deep past. We hope this will inspire further research from both communities on the deep circulation of the ocean," says Hutchinson.

Fukuoka, Japan - The threat of explosive volcanic eruptions looms over many cities around the world. Earthquakes, another major geological hazard, are known to have some relationships with the occurrence of volcanic eruptions. Although they often precede volcanic events, the mechanisms of these relationships are not yet well understood.

Mount Aso in Kyushu, Japan, is one of the largest active volcanoes in the world and has experienced major earthquakes and eruptions as recently as 2016. Researchers at Kyushu University's International Institute for Carbon-Neutral Energy Research (I2CNER) have been investigating the relationships among these events to better understand what are happening under the surface and to help predict future disasters. In particular, for a new study published in Geophysical Research Letters, they investigated "very long period" (VLP) seismic waves, which can represent pressure changes in subsurface hydrothermal systems.

"We analyzed continuous VLP seismicity data recorded from January 2015 to December 2016, a period that includes both large earthquakes and eruptions of Mount Aso," explains lead author of the study Andri Hendriyana. "Using on this dataset, we developed a differential-time back-projection method to accurately locate VLP events, and detected over 18,000 reliable VLP events."

Using this method, two distinct clusters of these seismic events were identified in the subsurface below the caldera of Mount Aso. For most of the observation period, VLP activity was almost entirely confined to the eastern cluster. However, after the Kumamoto earthquakes on April 2016, VLP activity abruptly shifted to the western cluster for about five months. Then, in September 2016, one month before the largest eruption of Mount Aso during the study period, VLP events migrated back to the eastern cluster. After the large eruption on October 8, 2016, VLP seismicity stopped temporarily. Together, these observations show that VLP events are affected by the occurrence of earthquakes and are related to volcanic eruptions. VLP seismicity is considered to be directly related to pressure variations associated with magmatic activity.

"We interpret the migration of VLP activity after the earthquakes as a response to permeability enhancement or to fractures opening because of extension associated with the Kumamoto earthquakes," says senior author Takeshi Tsuji. He expects this method to be applied in further studies of Mount Aso as well as other volcanoes worldwide.

"The information obtained from this new monitoring approach could reveal new details about the dynamic behavior within Aso and other volcanoes after earthquakes, and could provide important information for prevention and mitigation of future disasters."

Researchers at Rutgers and other institutions have discovered how muscle contraction (bronchospasm) in the airway, which cause breathing difficulty in people with asthma, occur by creating a microdevice that mimics the behavior of the human airways.

The study, published in the July 2019 issue of the journal Nature Biomedical Engineering and previously online, could lead to new treatment strategies for respiratory diseases, said co-author Reynold Panettieri, director of the Rutgers Institute for Translational Medicine and Science.

Bronchospasm can occur in both healthy people and those who suffer from serious respiratory diseases such as asthma or chronic obstructive pulmonary disease (COPD). Studying why the smooth muscle surrounding bronchial airways can suddenly contract and lead to difficulties in breathing is difficult due to the complexities of bronchospasm and the fact that the human respiratory system cannot be modeled in animal studies.

To analyze the biochemical and mechanical signals that occur between cells during spasms, the researchers created a microdevice -- a "bronchi on a chip" one-thousandth the size of a human hair -- containing cells from healthy and asthmatic lungs that mimics the function of a lung on single-cell levels.

When they triggered a simulated bronchospasm on the device, the researchers discovered that the initial contraction prompts the secretion of hormone-like compounds that either can induce an additional constriction or relax the spasm. In people with asthma, the smooth muscle surrounding the airways is more reactive and contracts more easily in response to stimuli such as allergens, leading to extended bronchial spasms, wheezing and shortness of breath.

They also found that inducing a second asthmatic trigger during a bronchial spasm at a precise time will actually cause the smooth muscle to relax and stop the spasm.

The treatments for bronchospam have not changed in the past 50 years, Panettieri said, since they work for most -- but not all -- people. "The microdevice allowed us to drill down into how single cells interact with each other in relation to smooth muscle contraction in a variety of lung diseases," said Panettieri. "Being able to study the mechanics on the single-cell level and view thousands of cells simultaneously can be an important screening tool for the development of new drugs for people with asthma who don't respond to current treatment."

They're physically and emotionally wounded - most likely suffering from post-traumatic stress. Members of the United States military who serve abroad often return to the U.S. to treat their injuries and must be transported by aeromedical evacuation between medical facilities. Those who undergo these types of evacuations are in states of both chronic and acute stress.

While much is known about the benefits of animal-assisted interventions in a variety of health care settings, there is limited evidence of the biological and psychosocial effects of this form of interaction in the military population, particularly in an aeromedical staging facility setting.

A study led by a Florida Atlantic University researcher in the Christine E. Lynn College of Nursing, Cheryl A. Krause-Parello, Ph.D., R.N., and collaborators, sought to test the feasibility and effectiveness of animal-assisted interventions to reduce stress in aeromedical staging facilities. For the study, they teamed up with a local not-for-profit animal organization that trains therapy dogs to visit health care facilities, libraries, and other community based settings with a certified dog handler.

"We know that stress can impede healing, which is why it's so important for practicing clinicians in aeromedical staging facilities and other health care settings to examine ways to reduce patient stress," said Krause-Parello, senior author, founder and director of Canines Providing Assistance to Wounded Warriors (C-P.A.W.W.) at FAU, the Sharon Phillips Raddock Distinguished Professor of Holistic Health in FAU's Christine E. Lynn College of Nursing, and a faculty fellow in FAU's Institute for Human Health and Disease Intervention (I-HEALTH), one of the university's four research pillars. "If animal-assisted intervention is effective in reducing stress, then this novel, innovative, and noninvasive intervention could easily be incorporated into these and other military settings."

For the study, recently published in the journal Stress and Health, the researchers examined the stress biomarkers cortisol, which affect the cardiovascular system and result in higher blood pressure, alpha-amylase, an enzyme, and immunoglobulin A, a blood protein that impacts the immune system, which were collected at regular intervals. The study sample included 120 military members ages 18 to 55 years old who were undergoing aeromedical evacuation. The majority of the male and female participants were in the Army (56.2 percent) followed by the Air Force (30.6 percent), Navy (7.4 percent), and Marine Corps (5 percent).

Results showed that an animal-assisted intervention in aeromedical staging facilities is both feasible and effective at reducing stress. Cortisol levels decreased significantly in the study participants following a 20-minute animal-assisted intervention. Patients with higher post-traumatic stress had a greater reduction in stress associated with immunoglobulin A, compared to those in the control group. Patients who participated in animal-assisted intervention experienced greater decreases in stress biomarkers than those who participated in the control group, regardless of post-traumatic stress symptom severity.

"The response to the animal-assisted intervention in our study was overwhelmingly positive," said Krause-Parello. "Study participants told us that they enjoyed interacting with the dogs, and the staff at the aeromedical staging facility also enjoyed visits from the dogs and their handlers."

Chronic stress is associated with increased morbidity and mortality from numerous physical and mental health disorders including heart disease, kidney disease, stroke, diabetes, obesity, ulcer, depression, anxiety, and post-traumatic stress disorder (PTSD).

"Results from this cutting-edge, nurse-led study by Dr. Krause-Parello and her colleagues offer promising, significant contributions to the field and to the military to support care of wounded service members. The finding that the animal-assisted intervention significantly reduced stress levels in post-traumatic stress symptom severity is powerful, especially in light of high rates of PTSD, cost of treatment, and the related co-morbidities," said Safiya George, Ph.D., R.N., dean of FAU's Christine E. Lynn College of Nursing.