Culture

Lung lining fluid key to elderly susceptibility to tuberculosis disease

image: Elderly alveolar lining fluid-exposed Mycobacterium tuberculosis (Mtb) demonstrates increased Mtb-induced immunopathology in the lung.

Image: 
Texas Biomedical Research Institute

San Antonio, Texas (August 7, 2019) - Old lungs are not as capable as young lungs of fighting off an infection of the bacteria that causes tuberculosis (TB), placing seniors at a greater risk of developing TB. The microbe that causes this infectious disease, Mycobacterium tuberculosis (Mtb), currently kills more people in the world than any other pathogen.

"Things go wrong as we get older," said Professor Joanne Turner, Ph.D., Vice President for Research. "When we're younger, we have control mechanisms in place, and our body will switch on responses and switch off responses as needed. As we get older, some of those responses become defective."

Texas Biomed researchers published an article in the Journal of Infectious Diseases in July 2019. The study details an experiment that took place in vitro (in the lab) and in vivo (in animals) that showed fluid in the lining of the lungs plays a big role in the elderly's susceptibility to infection with the bacterium Mtb.

The team studied the role of the lung mucosa (a.k.a., alveolar lining fluid), which is the layer of liquid in the lungs that assists in gas exchange and also plays a protective role against infection. Those samples were acquired from volunteers who underwent a bronchoalveolar lavage, a medical procedure in which a bronchoscope is passed through the mouth or nose into the lungs and fluid is squirted into a small part of the lung and then collected for examination. Half of the donor volunteers were from San Antonio; the other half were from Ohio. In San Antonio, Texas Biomed researchers are collaborating with the Pulmonary and Critical Care Medicine Division at UT Health San Antonio, Drs. Jay Peters and Diego Maselli Caceres.

Researchers incubated Mtb with this fluid at its physiological concentrations within the human lung. In healthy, young donors, the molecules in the lung lining fluid would interact with Mtb send bacteria to macrophages (immune cells) to be killed. However, in older donors, the molecules in the lung lining fluid present some dysfunctionalities, allowing bacteria to infect and grow within macrophages, thus driving susceptibility and higher risk of infection.

When the same experiment was conducted in vivo in healthy young mice, results recapitulated what happened in the in vitro experiment. The animals that received Mtb that had been incubated in lung lining fluid from older humans could not control the infection as well as animals that received Mtb incubated with lung lining fluid from a younger person.

"We hypothesized that the status of the lung mucosa may partially explain why we are susceptible to respiratory infectious diseases as we age," explained Professor Jordi Torrelles, Ph.D., Co-lead of the Population Health program at Texas Biomed. "Elderly individuals (65 and older) have higher degree of oxidation in their lung mucosa. In our study we demonstrated that this oxidation alters the normal function of important lung mucosa innate soluble components involved in the control of infectious agents reaching our lungs. With this control impaired as we age, we are more susceptible to respiratory infections. We are currently collaborating with Southwest Research Institute investigators (Drs. Hong Dixon and Varsin Archer) to establish if reversal of the oxidative status of the lung mucosa in the elderly could make us resistant to respiratory infections."

Scientists will be looking at ways to intervene in this process to make these molecules in the lungs of elderly people more functional.

"The most exciting thing this study tells us is that the very first interaction between a pathogen and the fluid in the lung can dictate long term outcome," Dr. Turner said. "You could perform lots of interventions throughout the entire infection period. But if you change that first interaction, you could potentially dictate whether that person develops active TB, controls it better or even clears it."

Credit: 
Texas Biomedical Research Institute

Scientists reveal key insights into emerging water purification technology

image: Cross-sectional view of a conventional hydrophobic membrane used in membrane distillation. The blue represents water.

Image: 
Tong and Kota labs/Colorado State University

With water scarcity a critical challenge across the globe, scientists and engineers are pursuing new ways to harvest purified water from unconventional sources, like seawater or even wastewater.

One of those researchers is Tiezheng Tong, an assistant professor in the Department of Civil and Environmental Engineering, whose lab is studying an emerging technology called membrane distillation.

Membrane distillation involves a thin, water-repellant membrane that exploits vapor pressure differences between hotter impure liquid, called "feedwater," and colder purified water, called "permeate." During the process, water vapor passes through the membrane and is separated from the salty or dirty feedwater. According to Tong, membrane distillation works better than other technologies like reverse osmosis, which can't treat extremely salty water such as desalination brines or produced water from hydraulic fracturing.

While it holds promise, membrane distillation doesn't work perfectly. A key challenge is designing membranes to purify water efficiently while ensuring zero contamination of the clean water.

Tong and materials scientist Arun Kota in the Department of Mechanical Engineering joined forces to get at the fundamental science behind designing that perfect membrane. In new experiments they describe in Nature Communications, the CSU researchers offer new information into why certain membrane designs used in membrane distillation work better than others.

"The fundamental knowledge from our paper improves mechanistic understanding on the water-vapor transport within microporous substrates and has the potential to guide the future design of membranes used in membrane distillation," Tong said.

In membrane distillation, the feedwater is heated, separating the pure and impure components by differences in volatility. The micro-porous membrane is a key component to the setup because it allows water vapor through, but not the entire impure liquid. Typically, the membrane is made of a "hydrophobic," or water-repellant, material in order to let only the water vapor pass through but maintain a barrier for the feedwater.

However, these hydrophobic membranes can fail, because the feedwater, such as shale oil-produced water, can have low surface tension. This low surface tension allows the feedwater to leak through the membrane pores, contaminating the pure water on the other side - a phenomenon called membrane wetting.

Previous research had unveiled that using "omniphobic" membranes - membranes that repel all liquids, including water and low surface tension liquids - keep the vapor/water separation intact. But, omniphobic membranes typically slow down the rate and amount of water vapor passing through the membrane, dramatically reducing the efficiency of the entire process.

The CSU researchers set out to discover why this tradeoff between hydrophobic vs. omniphobic membranes exists. Through systematic experiments in the lab led by postdoctoral researchers Wei Wang in Kota's lab, and Tong's graduate student Xuewei Du, they found that conventional hydrophobic membranes create a larger liquid-vapor interfacial area. This increases the amount of evaporation taking place. With the omniphobic membranes, they saw a much smaller liquid-vapor interface. This explains the difference between the membranes' performances.

The omniphobic membranes used in the experiments were made without depositing extra particles. Thus the researchers were able to determine that their observations weren't the result of structural changes to the membranes.

While they didn't offer a solution to the tradeoff, their insights reveal the core challenge around making membrane distillation a successful technology. "If you understand the problem thoroughly, then there is scope for solving it," Kota said. "We have identified the mechanism; now we have to solve the tradeoff problem."

For example, smart membranes with exceptional omniphobicity and simultaneously large liquid-vapor interfacial area can render membrane distillation a robust and cost-effective process for water purification. More collaborative research has been initiated by the team to design such smart membranes, with the goal of increasing efficiency of membrane distillation.

Tong added that the research happened at the interface of two disciplines: surface science and membrane technology.

"Arun and I utilized our complementary expertise to systematically conduct this work," Tong said. "It is an example of good interdisciplinary collaboration across campus."

Credit: 
Colorado State University

Right or left, Americans value hard work to achieve success

ITHACA, N.Y. - Conservatives and liberals may agree on at least one thing: the importance of working hard in order to succeed.

Liberals and Democrats are far more inclined than conservatives and Republicans to believe in the importance of equity - the notion that some groups may need different opportunities to succeed based on their starting point, so that all groups have the same levels of success.

But when it comes to proportionality - the idea that effort determines success - the researchers found a much smaller political divide. The paper, "All Things Being Equal: Distinguishing Proportionality and Equity in Moral Reasoning," was published in Social Psychological and Personality Sciences. The paper's senior author is Jeff Niederdeppe, associate professor of communication.

"This speaks to why we see so much value in American society placed on picking yourself up by your bootstraps to overcome any obstacle," said first author Christofer Skurka. "Notions of meritocracy and what is sometimes called the 'Protestant work ethic' are really interwoven into the American fabric, almost regardless of a person's political orientation."

In the study, around 3,000 participants from the United States filled out a 42-item questionnaire. They rated the extent to which they believe different circumstances impact their moral judgments ("Whether or not someone showed a lack of respect for authority") and rated the relevance of statements such as, "Respect for authority is something all children need to learn." Participants reported their political views and party affiliations, as well as their gender, age, education, race and ethnicity.

The researchers found that people on the political left care much more about equity than those on the right, explaining why liberals are more likely to support policies such as affirmative action and public assistance, which aim to correct imbalances.

The study also found that while conservatives generally care more about proportionality than liberals do, liberals also value it highly. Understanding what contributes to concepts of fairness can help policymakers frame conversations in terms that will resonate across different groups.

"There's quite a bit of political polarization that we see around public policy, and we often see political partisans talking past each other," Skurka said. "So, by understanding the different moral foundations on which these partisans base their moral judgments, we can better understand why they support certain kinds of initiatives and not others, and how we might be able to rally support for different initiatives."

Credit: 
Cornell University

Study finds fish preserve DNA 'memories' far better than humans

image: Cells transmitting information to the next generation in fish (highlighted green) do not erase memory attached to DNA as humans do.

Image: 
University of Otago

We are all familiar with the common myth that fish have poor memory, but it turns that their DNA has the capacity to hold much more memory than that of humans.

In a study published recently in the journal Nature, University of Otago researchers report that memory in the form of 'DNA methylation' is preserved between generations of fish, in contrast to humans where this is almost entirely erased.

DNA is often compared to a large book, with the words representing an instruction manual for life. DNA methylation encodes additional information that we are only starting to understand - a little like discovering handwritten notes in the margins of the book saying which pages are the most important, or recording newly acquired information. In humans, these notes are removed at each generation but this apparently does not occur in fish.

First author of the study, University of Otago Anatomy PhD student Oscar Ortega elaborates; "Methylation sits on top of DNA and is used to control which genes are turned on and off. It also helps to define cellular identity and function. In humans and other mammals, DNA methylation is erased at each generation; however, we found that global erasure of DNA methylation memory does not occur at all in the fish we studied."

In recent years much attention has been paid to the idea that significant events such as war or famine can have a lasting effect on subsequent generations through the inheritance of altered DNA methylation patterns. While these 'transgenerational' DNA memory effects appear to be potentially important, because of DNA methylation erasure events during development, it is thought to be extremely rare in humans. However, because fish apparently do not have these erasure events, it seems possible they can transmit life experience through their DNA in the form of methylation.

Dr Tim Hore, research team leader and Senior Lecturer, at Otago's Department of Anatomy, says the study's findings provide new avenues for scientists to study how the memory of events in one generation, can be passed on to the next.

"Mammalian biologists have searched long and hard to find reliable examples of where altered DNA methylation patterns are passed on to subsequent generations; yet only a handful have been verified in repeated studies. However, unlike humans, DNA methylation is not erased at each generation in at least some fish. So, we think intergenerational memory transfer through DNA methylation could be much more common in fish," Dr Hore says.

Also published in Nature Communications is a complementary study from the Garvin Institute (Australia), confirming the Otago observations.
"It is really great to have immediate validation that our results are robust - they used different techniques and developmental samples, but came to the same conclusions as we did," Dr Hore adds.

The researchers hope this new knowledge into DNA methylation inheritance will drive new understanding into what molecular secrets are passed from parents to their offspring, ultimately, rewriting the book of life as we know it.

Credit: 
University of Otago

Kappa opioid receptor influences naltrexone's effects on drinking alcohol

Philadelphia, August 6, 2019 - Researchers at Yale University have identified how naltrexone, a medication used to treat alcohol use disorder, reduces craving and consumption in heavy drinkers. The findings appear in Biological Psychiatry published by Elsevier. Although naltrexone is an approved treatment for alcohol use disorder, it only works in some people, which has led doctors to stop prescribing the drug. The new findings provide a better understanding of how naltrexone works in the brain, which could help identify people who would benefit from the treatment.

Although naltrexone binds to multiple molecules in the brain, first author Bart de Laat, PhD, and his senior colleagues Evan D. Morris, PhD, and Suchitra Krishnan-Sarin, PhD, in the Department of Radiology and Biomedical Imaging, and the Department of Psychiatry, focused on one of its targets, the kappa opioid receptor, to see if the molecule influences alcohol drinking and how much people want to drink alcohol.

Heavy drinkers with more kappa opioid receptors in the brain experienced a greater urge to drink alcohol. They also responded less to naltrexone treatment, meaning they continued to drink the same amount after receiving naltrexone.

"Kappa opioid receptor activation has been implicated in the 'dark side of addiction', in this case the motivation to drink even when alcohol is no longer rewarding. This innovative study makes the case that some therapeutic effects of naltrexone may be mediated by its effects on this target," said John Krystal, MD, Editor of Biological Psychiatry.

The researchers performed the study in non-treatment-seeking heavy drinkers who were allowed to self-administer alcoholic drinks before and after a week of naltrexone treatment. The findings are the first to reveal the role of the kappa opioid receptor in naltrexone's effect on craving and drinking in people with alcohol dependence.

"These results are an important step forward in our understanding of alcohol-related behaviors and how naltrexone functions. They highlight the importance of the kappa opioid receptor in alcohol use disorders and its treatment," said Dr. De Laat.

Other biological variables likely affect how well naltrexone works in different people, and more research is needed to discover who will or will not benefit from naltrexone treatment, Dr. De Laat added. But the new findings help advance understanding of the neurobiology of drinking problems and how to better treat them.

Credit: 
Elsevier

New hormone injection aids weight loss in obese patients

The findings came from a small study in which patients lost on average 4.4kg and the treatment led to substantial improvements to their blood glucose, with some patients' reducing to near-normal levels.

Obesity is a common problem in the UK and it is estimated that one in four adults are obese.

One of the most common types of weight loss surgery is a procedure known as gastric bypass surgery, which can be very effective in keeping excess weight off and improving blood sugar levels in diabetics. However, some patients decide against surgery and the procedure can cause complications such as abdominal pain, chronic nausea, vomiting and debilitating low blood sugar levels.

Previous research by Imperial College London suggested that one of the reasons why gastric bypass surgery works so well is because three specific hormones originating from the bowels are released in higher levels. This hormone combination, called 'GOP' for short, reduces appetite, causes weight loss and improves the body's ability to use the sugar absorbed from eating.

Researchers wanted to see if infusing patients with the GOP hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin and peptide, to mimic the high levels seen after surgery, could aid weight loss and reduce high glucose levels.

Fifteen patients were given the GOP treatment for four weeks using a pump that slowly injects the GOP mixture under the skin for 12 hours a day, beginning one hour before breakfast and disconnecting after their last meal of the day. Patients also received dietetic advice on healthy eating and weight loss from a dietician.

Professor Tricia Tan, Professor of Practice (Metabolic Medicine & Endocrinology) at Imperial College London and lead author of the study, said:

"Obesity and type 2 diabetes can lead to very serious and potentially life-threatening conditions such as cancer, stroke and heart disease. There is a real need to find new medicines so we can improve and save the lives of many patients. Although this is a small study our new combination hormone treatment is promising and has shown significant improvements in patients' health in only four weeks. Compared to other methods the treatment is non-invasive and reduced glucose levels to near-normal levels in our patients."

The work, published in Diabetes Care and presented at the American Diabetes Association 79th Scientific Sessions meeting at San Francisco, took place at Imperial College London in collaboration with University of Copenhagen and University College Dublin. The treatment was trialled on patients at the National Institute for Health Research Imperial Clinical Research Facility at Hammersmith Hospital, part of Imperial College Healthcare NHS Trust.

Twenty-six obese patients with prediabetes (when blood glucose is too high but not high enough to be classified as diabetes) and those with diabetes were recruited to the study at Hammersmith Hospital from July 2016 to October 2018. Fifteen patients were randomly selected to receive the hormone treatment and 11 patients were given a saline (salt water) infusion as a placebo over a four-week period. The team also recruited 21 patients who had undergone bariatric surgery and 22 patients who followed a very low-calorie diet to compare the results of GOP. All patients were given a glucose monitoring device to track their glucose levels following treatment.

In the trial, patients on the GOP treatment lost an average of 4.4kg, compared with 2.5kg for participants receiving a saline placebo. The treatment also had no side effects.

However, patients who received bariatric surgery or who followed a very low calorie diet lost significantly more weight than GOP patients. The changes in weight were 10.3kg for bariatric patient and 8.3kg for patients who followed a very low calorie diet.

Professor Tan commented: "Although the weight loss was smaller, using the GOP infusion would be preferable as it has fewer side effects than bariatric surgery. This result shows that it is possible to obtain some of the benefits of a gastric bypass operation without undergoing the surgery itself. If further trials are successful, in future we could potentially give this type of treatment to many more patients."

The team also found that GOP was capable of lowering blood glucose levels to near-normal levels, with little variation in the blood glucose. Patients who received bariatric surgery also had an overall improvement in blood glucose, but the levels were much more variable, leaving them vulnerable to low blood glucose levels.

The team aim to carry out a larger clinical trial to assess the impact of GOP on more patients over a longer period of time.

The research was funded by the UK Medical Research Council (MRC) and the NIHR Imperial Biomedical Research Centre.

This research is an example of the work carried out by Imperial College Academic Health Science Centre, a joint initiative between Imperial College London and three NHS hospital trusts. It aims to transform healthcare by turning scientific discoveries into medical advances to benefit local, national and global populations in as fast a timeframe as possible.

Credit: 
Imperial College London

Scientists shed new light on how we perceive vibrations through touch

Researchers have demonstrated a universal decoding system in humans that determines how we perceive vibrations of different frequencies through touch.

Their findings, published in eLife, suggest that this decoding system overrules our tactile sensory channels when we perceive vibrotactile stimuli. The system depends on neural discharge (or spike) patterns, regardless of the type of receptor that receives the stimuli, challenging well-established ideas of how we process these sensations.

The different skin regions on our bodies, such as on our heads, lips and fingertips, differ in their types of touch receptors. In the fingertip alone, there are four different ways of sensing touch: one receptor is more sensitive to pressure, another to stretch and two others respond to slow or fast vibrations. The touch receptor known as the Pacinian corpuscle is incredibly sensitive, and it is well-known that such sensors allow us to feel fast skin vibrations.

Now, the research team from Neuroscience Research Australia (NeuRA) in Sydney, has found a way to trick these receptors to respond to the slow vibrations that are mainly signalled by a different receptor type.

"The currently established view is that feeling a vibration through touch evokes two different sensations, subserved by two distinct receptor types, Meissner's and Pacinian corpuscle, which may engage different neural processing channels and play different biological roles," says first author Ingvars Birznieks, Associate Professor at the University of New South Wales (UNSW) Sydney and Senior Research Fellow at NeuRA. "These two systems have been labelled as Pacinian and non-Pacinian channels. Our study now challenges the idea of how these channels work within the tactile sensory system."

Birznieks and his team recruited healthy volunteers aged 20 to 26-years-old and without any known history of neurological disorders which would affect their somatosensory system. Using brief low-frequency vibratory stimuli to selectively activate the Pacinian channels in the participants, the scientists confirmed that only Pacinian receptors were responding to the tiny tapping movements on the skin. The team could then test what the human brain understands from signals coming through a different sensory channel than the normal route.

"To our surprise, we found that the brain didn't seem to care which channel and receptor this information came from - it was all processed in the same way," explains senior author Richard Vickery, also Associate Professor at UNSW Sydney. "As the receptor type appeared not to matter, it meant that the different skin regions with their different receptors can all cause the same brain sensations. This suggests a universal frequency decoding system, possibly explaining why we feel vibrations in the same way across the whole body."

Vickery adds that the findings indicate the need to review the foundations on which processing of vibrotactile stimuli is attributed to Pacinian and non-Pacinian channels.

"In the longer term, continuously improving our understanding of how such neural signal processing works in the brain could help in the development of more effective bionic limbs that enable real-time touch sensation," he concludes.

Credit: 
eLife

Wits University PhD student discovers new species of early dinosaur

image: Micro-CT scan of Ngwevu intloko skull

Image: 
Kimberley Chapelle/Wits University

A PhD student of the University of the Witwatersrand, South Africa, has discovered a new dinosaur species in the University's vaults, after it has been laying misidentified in a collection for 30 years.

The team of scientists, led by PhD Student Kimberley Chapelle, recognised that the dinosaur was not only a new species of sauropodomorph, but an entirely new genus. The specimen has now been named Ngwevu intloko which means "grey skull" in the Xhosa language, chosen to honour South Africa's heritage. She was joined in the research by her PhD supervisors: Prof Jonah Choiniere (Wits), Dr Jennifer Botha (National Museum Bloemfontein), and Professor Paul Barrett (Natural History Museum, London). Together, Kimberley and these world-leading researchers have been improving knowledge of South African palaeontology for the last six years. The dinosaur has been described in the academic journal, PeerJ.

Professor Paul Barrett, Chapelle's PhS supervisor and researcher at the Natural History Museum in the UK explains, "This is a new dinosaur that has been hiding in plain sight". "The specimen has been in the collections in Johannesburg for about 30 years, and lots of other scientists have already looked at it. But they all thought that it was simply an odd example of Massospondylus."

Massospondylus was one of the first dinosaurs to reign at the start of the Jurassic period. Regularly found throughout southern Africa, these animals belonged to a group called the sauropodomorphs and eventually gave rise to the sauropods, a group containing the Natural History Museum's iconic dinosaur cast Dippy. Researchers are now starting to look closer at many of the supposed Massospondylus specimens, believing there to be much more variation than first thought.

Kimberley Chapelle explains why the team were able to confirm that this specimen was a new species, "In order to be certain that a fossil belongs to a new species, it is crucial to rule out the possibility that it is a younger or older version of an already existing species. This is a difficult task to accomplish with fossils because it is rare to have a complete age series of fossils from a single species. Luckily, the most common South African dinosaur Massospondylus has specimens ranging from embryo to adult. Based on this, we were able to rule out age as a possible explanation for the differences we observed in the specimen now named Ngwevu intloko."

The new dinosaur has been described from a single fairly complete specimen with a remarkably well-preserved skull. The new dinosaur was bipedal with a fairly chunky body, a long slender neck and a small, boxy head. It would have measured three metres from the tip of its snout to the end of its tail and was likely an omnivore, feeding on both plants and small animals.

The findings will help scientists better understand the transition between the Triassic and Jurassic period, around 200 million years ago. Known as a time of mass extinction it now seems that more complex ecosystems were flourishing in the earliest Jurassic than previously thought.

"This new species is interesting," says Prof Barrett, "because we thought previously that there was really only one type of sauropodomorph living in South Africa at this time. We now know there were actually six or seven of these dinosaurs in this area, as well as variety of other dinosaurs from less common groups. It means that their ecology was much more complex than we used to think. Some of these other sauropodomorphs were like Massospondylus, but a few were close to the origins of true sauropods, if not true sauropods themselves."

This work shows the value of revisiting specimens in museum collections, as many news species are probably sitting unnoticed in cabinets around the world.

Credit: 
University of the Witwatersrand

Dead planets can 'broadcast' for up to a billion years

Astronomers are planning to hunt for cores of exoplanets around white dwarf stars by 'tuning in' to the radio waves that they emit.

In new research led by the University of Warwick, scientists have determined the best candidate white dwarfs to start their search, based upon their likelihood of hosting surviving planetary cores and the strength of the radio signal that we can 'tune in' to.

Published in the Monthly Notices of the Royal Astronomical Society, the research led by Dr Dimitri Veras from the Department of Physics assesses the survivability of planets that orbit stars which have burnt all of their fuel and shed their outer layers, destroying nearby objects and removing the outer layers of planets. They have determined that the cores which result from this destruction may be detectable and could survive for long enough to be found from Earth.

The first exoplanet confirmed to exist was discovered orbiting a pulsar by co-author Professor Alexander Wolszczan from Pennsylvania State University in the 1990s, using a method that detects radio waves emitted from the star. The researchers plan to observe white dwarfs in a similar part of the electromagnetic spectrum in the hope of achieving another breakthrough.

The magnetic field between a white dwarf and an orbiting planetary core can form a unipolar inductor circuit, with the core acting as a conductor due to its metallic constituents. Radiation from that circuit is emitted as radio waves which can then be detected by radio telescopes on Earth. The effect can also be detected from Jupiter and its moon Io, which form a circuit of their own.

However, the scientists needed to determine how long those cores can survive after being stripped of their outer layers. Their modelling revealed that in a number of cases, planetary cores can survive for over 100 million years and as long as a billion years.

The astronomers plan to use the results in proposals for observation time on telescopes such as Arecibo in Puerto Rico and the Green Bank Telescope in West Virginia to try to find planetary cores around white dwarfs.

Lead author Dr Dimitri Veras from the University of Warwick said: "There is a sweet spot for detecting these planetary cores: a core too close to the white dwarf would be destroyed by tidal forces, and a core too far away would not be detectable. Also, if the magnetic field is too strong, it would push the core into the white dwarf, destroying it. Hence, we should only look for planets around those white dwarfs with weaker magnetic fields at a separation between about 3 solar radii and the Mercury-Sun distance.

"Nobody has ever found just the bare core of a major planet before, nor a major planet only through monitoring magnetic signatures, nor a major planet around a white dwarf. Therefore, a discovery here would represent 'firsts' in three different senses for planetary systems."

Professor Alexander Wolszczan from Pennsylvania State University, said: "We will use the results of this work as guidelines for designs of radio searches for planetary cores around white dwarfs. Given the existing evidence for a presence of planetary debris around many of them, we think that our chances for exciting discoveries are quite good."

Dr Veras added: "A discovery would also help reveal the history of these star systems, because for a core to have reached that stage it would have been violently stripped of its atmosphere and mantle at some point and then thrown towards the white dwarf. Such a core might also provide a glimpse into our own distant future, and how the solar system will eventually evolve."

Credit: 
University of Warwick

Houseplants ability to survive drought can provide useful knowledge for the climate change era

image: Dehydrated Aloe Vera

Image: 
Louise Isager Ahl

Researchers from the Natural History Museum of Denmark and the Department of Plant and Environmental Sciences at the University of Copenhagen, have in collaboration with researchers at the Royal Botanic Gardens Kew in England, demonstrated that certain Aloe species shrink, or more scientifically speaking - fold - their cell walls together. In doing so, the plants preserve resources during drought. Concurrently, the carbohydrate (polysaccharide) composition of their cell walls are altered. The results have just been published in the journal Plant, Cell and Environment.

"Our results tie changes in carbohydrate composition with the Aloe plant's ability to manage extended periods of drought. It is highly relevant, that we understand the physiological mechanisms that allow certain plants to survive under extreme conditions, due to climate change and the potential for severe climatic fluctuations," says plant biologist Louise Isager Ahl of the Natural History Museum of Denmark.

Useful genetic traits

The majority of succulents can survive in areas susceptible to shorter or extended periods of drought. This ability has made succulents popular as houseplants. Aloe vera, along with other Aloe species, have a special tissue in the middle of their leaves known as the hydrenchyma. This tissue has a well-developed ability to control water content in leaves.

One of the mechanisms that succulents use to resist drought is to fold their cell walls together during dehydration and unfold them again as water becomes available. The unique composition of carbohydrates in the cell walls and within the cells of the hydrenchyma is partly responsible for these plants' ability to regulate and retain water. It is a trait that may be transferable to other plants.

"I can imagine that by identifying and understanding the genetic mechanisms allowing Aloe species to fold and unfold their cell walls, we will be able to integrate similar mechanisms into crops to make them more resilient to climate change," says Louise Isager Ahl.

The purple line shows the Aloe Vera cell wall when it is dehydrated and folded.

The bottom half shows the Aloe Vera cell wall when it is hydrated.

Results based on 100-year-old observations

The first descriptions of succulent plant species with folded cell walls were made by a German botanist at the end of the 19th century. His observations were investigated further by another German botanist at the beginning of the 20th century. Since then, few researchers have delved into the underlying mechanisms behind cell wall folding. Not until Louise Isager Ahl and Jozef Mravec wondered if there might be a correlation between the changes they observed in carbohydrate composition and the folding of cell walls. Together, they began studying the composition of carbohydrates in Aloe plants, both before and after droughts.

"The ability to survive drought by cell wall adaptations is also found in other succulents, but the changes in carbohydrate composition in Aloe, in relation to drought, had not previously been investigated in Aloes. The unique collaboration between botanists and carbohydrate chemists in this project has provided us with a better understanding of the composition and function of these carbohydrates in relation to the drought management abilities of these plants," says Louise Isager Ahl.

Credit: 
University of Copenhagen

Staring at seagulls could save your chips

video: This is a human looking away from a gull. The gull approaches and tries to take the food.

Image: 
University of Exeter

Staring at seagulls makes them less likely to steal your food, new research shows.

University of Exeter researchers put a bag of chips on the ground and tested how long it took herring gulls to approach when a human was watching them, compared to when the human looked away.

On average, gulls took 21 seconds longer to approach the food with a human staring at them.

The researchers attempted to test 74 gulls, but most flew away or would not approach - only 27 approached the food, and 19 completed both the "looking at" and "looking away" tests. The findings focus on these 19 gulls.

"Gulls are often seen as aggressive and willing to take food from humans, so it was interesting to find that most wouldn't even come near during our tests," said lead author Madeleine Goumas, of the Centre for Ecology and Conservation at Exeter's Penryn Campus in Cornwall.

"Of those that did approach, most took longer when they were being watched. Some wouldn't even touch the food at all, although others didn't seem to notice that a human was staring at them.

"We didn't examine why individual gulls were so different - it might be because of differences in "personality" and some might have had positive experiences of being fed by humans in the past - but it seems that a couple of very bold gulls might ruin the reputation of the rest."

Senior author Dr Neeltje Boogert added: "Gulls learn really quickly, so if they manage to get food from humans once, they might look for more.

"Our study took place in coastal towns in Cornwall, and especially now, during the summer holidays and beach barbecues, we are seeing more gulls looking for an easy meal. We therefore advise people to look around themselves and watch out for gulls approaching, as they often appear to take food from behind, catching people by surprise.

"It seems that just watching the gulls will reduce the chance of them snatching your food."

The UK's herring gulls are in decline, though numbers in urban areas are rising. Gulls in these areas are often considered a nuisance because of behaviours like food-snatching.

The researchers say their study shows that any attempt to manage this issue by treating all gulls as being alike could be futile, as most gulls are wary of approaching people. Instead, people might be able to reduce food-snatching by the few bold individuals by modifying their own behaviour.

The natural diet of herring gulls is fish and invertebrates, and the researchers will next investigate how eating human foods affects the gulls, and their chicks, in the long term. The paper, published in the journal Biology Letters, is entitled: "Herring gulls respond to human gaze direction."

Credit: 
University of Exeter

Most seniors with dementia live at home, despite pain, anxiety, poor health

Contrary to popular belief, most older Americans with advancing dementia remain in their own homes -- many until they die. But a new study by researchers at UC San Francisco has revealed that this population may endure more pain and have more complex or unaddressed medical needs than their counterparts in nursing homes.

In the study, researchers compared the medical characteristics of 728 adults over 65 with moderately severe dementia, in three settings: the participants' own homes; residential care, which spans the spectrum of retirement communities from those offering support at extra cost to assisted-living facilities; and nursing homes, which care for people unable to attend to their most basic needs.

Although the living-at-home participants had an average age of 82, four years younger than the nursing home residents, the researchers found that they had more chronic conditions -- 3.2 versus 3.1 -- were more likely to be bothered by pain -- 70.8 percent versus 58.6 percent -- and had fallen in the last month or had concerns about falls -- 67.1 percent versus 50.4 percent. Additionally, they were more likely to have anxiety and fair or poor health, rather than good or excellent health.

Seniors Turning Away from Nursing Facilities in Favor of Familiarity of Home

But the authors say the findings -- which appear in the Journal of the American Geriatrics Society on Aug. 7, 2019 -- should not be interpreted as a call to accelerate moving people with moderately severe dementia from their homes.

"Rates of nursing home use are declining because they are expensive and people generally prefer the familiarity of home," said first author Krista Harrison, PhD, of the UCSF Division of Geriatrics. "People with dementia benefit from consistent and predictable environments and caregivers. Nursing homes may offer more people to help with medical and social needs, but that might mean sharing a room with someone with different daily habits or distressing behavior symptoms."

In keeping with the trend away from nursing homes, Medicaid spending on community and home-based services has surpassed spending on institutional care, the authors noted.

The participants were drawn from a sample of Medicare enrollees, representative of seniors nationwide. Some 499 of the total participants lived at home (68.5 percent), 126 lived in residential facilities (17.3 percent) and 103 (14.2 percent) lived in nursing homes. In a 2015 study cited by the authors and drawn from a separate nationally representative sample of U.S. seniors, 58.7 percent with dementia were reported to have died in their homes.

To meet the criteria for moderately severe dementia, the study's participants had a doctor's diagnosis for dementia or were determined to have probable dementia according to a survey algorithm. Additionally, they had to struggle with at least one activity of daily living, such as dressing, bathing or toileting, and a "cognitively-oriented instrumental activity of daily living," such as managing medications or finances.

"At this stage of dementia, patients may have difficulty recalling their address or personal history," said senior author Alexander K. Smith, MD, MPH, from the UCSF Division of Geriatrics and the San Francisco Veterans Affairs Medical Center. "Communication becomes impaired and the individual may struggle to follow a conversation and become disoriented with respect to time and place. They may lack good judgment and experience mood and behavior changes."

Seniors in residential facilities with moderately severe dementia differed from those at home and in nursing homes. This group, whose average age was 85, had less depression and anxiety, fewer chronic conditions and less unintentional weight loss. However, the cost of residential care facilities, which average $48,000 a year, makes them prohibitive to most seniors for multi-year stays. While nursing homes are more expensive, depending on the state, Medicaid may cover seniors with particularly low income and assets, the authors said.

Seniors in Residential Care More Likely to Be Higher Income, Less Likely to Be Partnered

Not surprisingly, the seniors living in residential care had higher incomes and were more likely to be U.S.-born and have post-high-school education, compared to those living at home or in nursing facilities. Conversely, this group was significantly less likely to be married or living together (16.4 percent) compared to those living at home (45.1 percent) or in nursing facilities (21.8 percent).

Home-based medical care, in which insurance pays for coordinated home care provided by doctors, physician assistants or nurse practitioners and their interdisciplinary teams, is a small but growing portion of health care.

"Some people with dementia who live at home receive home-based primary, geriatric or palliative care, but many more likely do not," said Harrison, who is also affiliated with the UCSF Philip R. Lee Institute for Health Policy Studies. "There is an urgent need for these services -- as well as home health aides and other social supports -- to become widely available to those families providing home care for loved ones with dementia."

Studies indicate that just 12 percent of homebound people receive primary care in their homes, according to the authors. Such programs result in reductions in disability and depression, fewer visits to emergency departments, fewer hospital stays and long-term care admissions, as well as positive impacts on caregivers' health.

Credit: 
University of California - San Francisco

Amyloid is a less accurate marker for measuring severity, progression of Alzheimer's

image: PET imaging using the radiotracers FDG and florbetapir to quantify cognitive decline in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy controls

Image: 
Penn Medicine

(PHILADELPHIA) -While the presence of beta-amyloid plaques in the brain may be a hallmark of Alzheimer's disease, giving patients an amyloid PET scan is not an effective method for measuring their cognitive function, according to a new study from researchers in the Perelman School of Medicine at the University of Pennsylvania and Thomas Jefferson University. The researchers concluded that fluorodeoxyglucose (FDG) PET, which measures the brain's glucose consumption as a marker of neural activity, is a stronger approach for assessing the progression and severity of Alzheimer's and mild cognitive impairment (MCI) as compared to florbetapir-PET scans, which reveal amyloid protein deposits in the brain. This suggests that FDG-PET is also a better means for determining the effectiveness of Alzheimer's therapies, as well as tracking patients' disease advancement, in both clinical and research settings. Results of this study are detailed in the August issue of the Journal of Alzheimer's Disease.

"Both florbetapir-PET and FDG-PET are approved diagnostic methods for Alzheimer's disease, and both appear to be effective in indicating some sort of cognitive impairment. However, we have now shown that FDG-PET is significantly more precise in clinical studies, and it is also available for routine use with modest costs," said the study's co-principal investigator Abass Alavi, MD, PhD, a professor of Radiology at Penn. "Our results support the notion that amyloid imaging does not reflect levels of brain function, and therefore it may be of limited value for assessing patients with cognitive decline."

Alzheimer's disease, the most common cause of dementia, is the sixth leading cause of death in the United States, affecting up to 5.8 million Americans currently. As clinicians aim to spot and treat the symptoms of dementia in its earliest stages, PET plays an increasingly pivotal role in diagnosing and monitoring Alzheimer's disease, as well as MCI, a condition that often precedes dementia.

Two of the most significant biomarkers found in Alzheimer's are decreased glucose uptake and the accumulation of amyloid plaques in the brain. PET scans use different radioactive drugs, called radiotracers, to measure these biomarkers within the brain tissue of patients with cognitive impairment. FDG-PET is one of the most commonly used imaging techniques to diagnose Alzheimer's. However, in recent years, several other radiotracers, such as florbetapir, have been developed to detect the deposition of amyloid plaques.

Recently, the effectiveness of amyloid imaging as a strategy for monitoring dementia symptoms has been called into question. While the presence of amyloid plaques in the brain is considered as being characteristic of Alzheimer's, some studies have shown that large amounts of amyloid plaques were present in healthy, non-demented individuals. Conversely, recent clinical trials have shown that the intended removal of amyloid from the brains of patients with Alzheimer's disease led to no change in, or even worsened, cognitive performance.

In this study, the researchers evaluated 63 individuals, including 19 with clinically diagnosed Alzheimer's disease, 23 with MCI, and 21 healthy individuals. The study participants underwent both FDG- and florbetapir-PET imaging. They were then assessed with a Mini Mental Status Examination (MMSE), a widely used diagnostic test for detecting and assessing the severity of cognitive impairment. The researchers used a novel "global quantification approach" to generate data from five different regions of the brain, which were correlated with the results from the MMSE scores.

The study revealed that both FDG- and florbetapir-PET scans are able to effectively discriminate the individuals with dementia from the healthy control group. However, when compared with the MMSE scores, the correlation between low cognitive performance and high levels of amyloid was significantly weaker than the correlation between FDG and low cognitive performance for all groups included in the study. This suggests that FDG-PET is a more sensitive indicator of cognitive decline.

"Amyloid imaging has a value in diagnosing or ruling out Alzheimer's disease, but it's a bit like all or nothing. Our study shows that it can reveal disease, but you wouldn't be able to differentiate between someone who had very mild or very severe symptoms," said co-principal investigator Andrew Newberg, MD, a professor of Radiology at Thomas Jefferson University, who added that these findings have important implications for clinical research.

"In a clinical drug trial, for example, it may be more relevant to do an FDG-PET scan, rather than using amyloid as a marker, to find out whether the therapy is working," Newberg said.

While FDG-PET may not be a perfect diagnostic tool, the study confirms that currently it is the best available method for monitoring symptoms of dementia, according to Alavi.

"Right now, FDG is king when it comes to looking at brain function, not only in Alzheimer's disease, but also diseases like vascular dementia and cancer," Alavi said.

Credit: 
University of Pennsylvania School of Medicine

Hotter, wetter, dryer: WVU research forecasts an uptick in extreme weather, temperatures

image: Nicolas Zegre, director of the Mountain Hydrology Laboratory at WVU, analyzed seasonal changes in water and energy balances over the Appalachian region.

Image: 
West Virginia University

It's going to rain a lot in West Virginia. It's going to be really dry, too.

Huh?

While torrential downpours and flash flooding don't evoke images of drought or water insecurity, those polar opposites make sense in the erratic world of a warming climate, according to West Virginia University research.

Such instability could undermine the availability of food and water in West Virginia, further challenging an already economically struggling state.

Nicolas Zegre, director of the Mountain Hydrology Laboratory at WVU, analyzed seasonal changes in water and energy balances over the Appalachian region. Zeroing in on West Virginia, he projected that the following trends could occur by the end of the 21st century:

up to a 10-degree (Fahrenheit) jump in average temperature,

increased evaporation along mountain ridges,

more frequent droughts,

a rise in extreme events (i.e. heat waves, tornadoes, flooding).

Zegre's findings, published in the Journal of Applied Meteorology and Climatology, and funded through a National Science Foundation award to WVU, Marshall University and West Virginia State University, relied on a vast dataset featuring historical and future climate variables from 420 counties, 13 states and 20 major river basins in Appalachia.

The data represents a daily timescale from 1950 to 2100 and includes climate variables such as precipitation, temperature, evaporation, wind speed and humidity. Those variables wind up playing critical roles in water security, ecosystem health and economic supply chains, Zegre said.

The 10-degree spike in temperature is a worst-case scenario, expected if the amount of carbon emissions released into the environment continue at the current rate or increase. But if reducing emissions becomes a global priority, Zegre expects average temps to jump to 5 degrees instead of 10 degrees.

"Changes of these magnitudes may seem trivial but, in fact, they are not," said Zegre, an associate professor of forest hydrology in the Davis College of Agriculture, Natural Resources and Design.

One burning question to emerge from his research - 'How can there be drought if flooding and heavy precipitation are expected to rise?' - is explained by Zegre. Increased evaporation is the culprit. He compares the phenomenon of evaporation to how we sweat.

"Warmer air temperature provides more energy for evaporating water from Earth's surface, similar to how humans sweat more on warmer days," Zegre said. "The more energy we exert, the warmer our bodies are. We become dehydrated unless we drink more water. The same can be said for our ecosystem.

"Higher elevations are warming and drying at a faster rate. They see greater amounts of rainfall and are where streams and water sources that humanity relies on, begin. That means both precipitation and drought are expected. It's contrary to how we think about the predictability of the climate system."

The atmosphere expands under warmer conditions and increases the amount of water that can be stored exponentially (Think of a balloon expanding in warm air and shrinking in cooler air.). With more water stored in the atmosphere, frequent and intense storms are likely to occur, resulting in increased flooding, landslides and pollution.

Beyond these potential extreme weather events, a wealth of social problems can unfurl as a result.

Before entering academia at WVU, Zegre spent eight years in the U.S. Army and National Guard.

"I see climate change from a national security standpoint," he said. "Climate change is a 'threat multiplier.' Whether it be overseas conflict or reliable water supplies locally. It exacerbates unstable situations."

Zegre pointed at the influx of refugees flowing into Europe in recent years. The Syrian refugee crisis began after a prolonged drought collapsed that country's agriculture economy.

"There was no water, and very extreme temperatures," Zegre said. "As parts of the globe see more flooding and drier conditions, people seek better ways of life. Large-scale emigration from regions under threat presents very real challenges for receiving countries."

Even the Department of Defense conducts research on how climate change influences readiness, operations and security, Zegre said.

Water insecurity is another major concern. At the Mountain Hydrology Lab, Zegre and his team focus on the implications of environmental and climate change on fresh water security in mountain regions.

Droughts and variable weather events can make clean, reliable water a valuable, possibly scarce, commodity, especially to regions drying out faster than Appalachia.

The Appalachian Mountains produce a larger amount of precipitation and streamflow than the surrounding lower lying regions. Streamflow generated in West Virginia, for example, provides fresh water to roughly nine million people (or 3 percent of the U.S. population) in the Eastern and Midwestern U.S.

Zegre hopes his research can be utilized to form policy from an impartial standpoint that enhances quality of life in West Virginia in today's divided, partisan political world.

"Our bodies are the best environmental sensors we have," he said. "If we're open to observing what's happening around us, it's fairly obvious what is occurring.

"As a forester, I see how the growing season has changed. Our forests are putting leaves out earlier than what they used to. Anglers are seeing different insects hatching at different times. Kayakers are seeing creeks and streams flowing more often."

As another point, Zegre compared his time as an undergraduate student at WVU in the 1990s to living in Morgantown today.

"There were hardly any mosquitoes or ticks in Morgantown in the 1990s," he said. "Now they're everywhere.

"Understanding climate change and its impacts is critically needed for public discourse," he said. "It's crucial for developing well-informed citizens and necessary for promulgating policies and practices that protect West Virginians.

"We developed this dataset with the specific goal of providing the public, educators, businesses and decision makers with easy access to data, maps, and interpretation to understand and mitigate the consequences of climate change on quality of life in West Virginia."

Credit: 
West Virginia University

Pitt first to grow genetically engineered mini livers to study disease and therapeutics

image: Photograph of rat liver, stripped of rat-specific cells and re-seeded with engineered human liver cells.

Image: 
UPMC

PITTSBURGH, July 11, 2019 - Researchers at the University of Pittsburgh School of Medicine are the first to grow genetically modified miniature human livers in the laboratory, to emulate human liver disease progression and test therapeutics.

In a proof-of-concept paper published today in Cell Metabolism, Pitt researchers chronicle how they transformed genetically engineered human cells into functional, 3D liver tissue that mimics non-alcoholic fatty liver disease (NAFLD)--a condition involving fat buildup in the liver, which can lead to cirrhosis or even liver failure. With obesity rates in America climbing, NAFLD is quickly becoming the leading cause of chronic liver disease.

"This is the first time we can create genetically engineered human mini livers with a disease using stem cells in the lab," said senior author Alejandro Soto-Gutierrez, M.D., Ph.D., associate professor of pathology at Pitt's School of Medicine and faculty member of the McGowan Institute for Regenerative Medicine and the Pittsburgh Liver Research Center.

That's important not only for understanding what causes the disease and how it progresses, but also for testing therapeutics. It's common for drugs to fail in clinical trials, despite promising results in mice.

For instance, the drug Resveratrol, which acts on SIRT1 proteins commonly associated with NAFLD, was effective in mouse models, but failed in human clinical trials.

"Mice aren't humans," Soto-Gutierrez said. "We are born with certain mutations, polymorphisms, that will predispose us to certain diseases, but you can't study polymorphisms in mice, so making a mini customized human liver is advantageous."

First, the researchers genetically engineered normal human skin cells to express a chemically activated switch that could tamp down the SIRT1 gene. Then, they reprogrammed the cells back to their stem cell state and turned them into liver cells. After that, they seeded the genetically engineered human liver cells into rat livers stripped of their own cells, where they blossomed into functional 3D mini livers, with blood vessels and other structural features of a normal organ.

That structure is part of what distinguishes mini livers from 'organoid' cultures--tiny balls of cells that self-assemble to replicate simplified organ function--although the mini livers lacked the distinct zones of metabolic function that normal livers have.

Once the mini livers were mature, the researchers flipped the genetic switch to suppress the SIRT1 gene, and the bioengineered mini livers started to mimic the metabolic dysfunction observed in tissues from patients with fatty liver disease.

But just like the clinical trials, Resveratrol wasn't effective in the lab-grown livers either.

The key, Soto-Gutierrez explained, is that Resveratrol boosts the activity of SIRT1 proteins, not SIRT1 genes. If SIRT1 gene expression is suppressed--like it is in his bioengineered livers, and perhaps also NAFLD patients--there isn't any protein to act on, so the drug won't work. It's targeting the wrong step.

"That's an insight that could only come from studying functional human tissue," Soto-Gutierrez said.

Genetically engineered, lab-grown mini livers provide a ready and reliable test-bed for drugs at all stages of disease progression.

"These mini livers aren't ready for clinical applications like transplantation anytime soon, but I imagine in the future we can make human livers where you can order what kind of function you want, or even enhance function," Soto-Gutierrez added.

Credit: 
University of Pittsburgh