Culture

Melbourne researchers have identified what makes a specialised immune cell, known as mucosal-associated invariant T (MAIT), cells boost their numbers and attack foreign invaders at the site of the infection.

T cells are a core component of the immune system, which recognise the presence of infectious agents through surface structures known as T cell receptors.

While little is known about the exact role MAIT cells play, previous research from the Doherty Institute has shown they provide a layer of protection, which is particularly important if other arms of the immune system are compromised.

Using mouse models, University of Melbourne researchers from the Doherty Institute were able to identify the molecular signals to activate and expand MAIT cells following Salmonella or Legionella infection.

MAIT cells are in abundance in the human body (up to 10 per cent of the T cells in the blood), and differ from other T cells as they respond to vitamin-based metabolites (rather than peptides and lipids) that are generated when bacteria grow.

They also sit, ready to act, in tissue sites, such as the lungs; a frequent site of infection. However, normal healthy bacteria also make these vitamin-based molecules, so MAIT cell immunity must be tightly regulated by a range of molecular signals so that they respond only when necessary.

Identifying and exploiting the signals that activate MAIT cells during an infection could potentially be used for vaccination strategies or to block disease when MAIT cells are inappropriately activated through misrecognition of infectious agents.

"We found that IL-23, an inflammatory cell signalling protein, was the key to MAIT cells expanding their army and attacking the infection which, in our experiments, was in the lungs," Dr Huimeng Wang, lead author of the paper published today in Science Immunology.

"The models we used were quite definitive and the results were dramatic; we found that if you knock out the IL-23, there was very little MAIT cell response to the bacteria."

Co-senior author, Dr Alexandra Corbett, said they also looked at what would be the best way to prime MAIT cells to enhance protection through vaccination.

"If you add a vitamin metabolite molecule, plus IL-23 we can reconstitute this dramatic response of MAIT cells that you see during infection, which results in enhanced protection," Dr Corbett said.

"In the enhanced protection, we saw the bacteria were cleared earlier, and the numbers of bacteria were reduced 100-fold five days following infection. In the elderly or immunocompromised, which is where infections with bacteria such as Legionella cause problems, this could be the difference between life and death."

Co-senior author, Dr Zhenjun Chen, said MAIT cells are an arm of the immune system that demand close attention.

"We are continuing to gather evidence that MAIT cells will be excellent candidates to fight infection, and this research is one more piece in that puzzle," Dr Chen said.

Using a relevant animal model (pigs), University of Saskatchewan researchers have shown that mild Zika virus infection in fetuses can cause abnormal brain development in apparently healthy young animals.

The study, published Nov. 14 in PLOS Pathogens, provides new insights into the potential outcomes of Zika virus infection and could point to new prevention and treatment strategies to alleviate the long-term effects of Zika virus infection.

Spread by the bite of an infected Aedes species mosquito, Zika infection of pregnant mothers can lead to death and decreased brain size (microcephaly) in fetuses, leading to life-long developmental and cognitive impairment.

However, there is growing concern that sub-clinical infections (showing no symptoms) in pregnant mothers can result in brain disorders and delayed neurodevelopmental abnormalities in offspring after birth.

Using the pig as a model, new research at USask's Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) has provided direct evidence to support this concern.

"We have demonstrated in a relevant animal model that mild infection in fetuses results in abnormal brain development and impaired immunity in young pigs," said VIDO-InterVac Director Dr. Volker Gerdts who also participated in the study.

Some of the affected offspring also showed altered behaviour during stress.

"For the first time, we have shown that mild fetal infection can lead to sex-specific brain disease in offspring: male piglets showed more molecular brain abnormalities than female piglets," said Dr. Uladzimir Karniychuk, senior author of the study, who with colleagues developed the novel animal model.

"We are now able to better understand the disease in fetuses and how it affects health in offspring."

In 2016, the World Health Organization declared Zika virus a public health emergency. While this emergency declaration has been lifted, Zika infection remains a public health concern. There is currently no approved vaccine or therapy available to combat the infection.

Karniychuk said a next step is to develop an animal model for the study of how to treat and cure infections such as Zika virus in utero. There are currently no in utero therapies for congenital viral infections. Earlier this year, Karniychuk was awarded $250,000 over two years by the federal New Frontiers in Research Fund to undertake this work aimed at reducing the long-term consequences of abnormalities in developing fetuses and the treatment required after birth.

For almost 45 years, VIDO-InterVac has used large animal models to help understand how pathogens cause disease.

"This is another example of how models can improve our understanding of the health consequences of infection, and aid in the development of policy and medical interventions to reduce the long-term impact of infectious diseases," said Gerdts.

Researchers in Japan and the U.K. have discovered new details of how young leaves build their first chloroplasts, the energy factories of plant cells. The researchers identified a new role for a protein that was first identified 25 years ago, but had defied characterization until now.

When a new plant germinates from a seed and begins growing its first leaves, it is in a race of survival to build its chloroplasts. Without chloroplasts to convert sunlight into energy, that life-giving sunlight instead burns the plant from the inside out by producing harmful chemicals called reactive oxygen species. Building the chloroplasts requires a relay of communication signals between the developing chloroplast and the plant cell's central DNA center, the nucleus.

The protein that the researchers characterized, GUN1, was known to have an important role in this communication between chloroplast and nucleus, but the details of its role remained unclear.

"GUN1 has been a mystery for such a long time," said Professor Tatsuru Masuda from the University of Tokyo, leader of the ongoing research and final author of the recent publication in the Proceedings of the National Academy of Sciences.

GUN1 was previously difficult to study because, although plant cells make more of it throughout their lives, the protein is quickly degraded under sunlight.

The research team revealed that GUN1 influences the production and release of another proposed communication molecule.

During the first days of leaf development and times without sunlight, GUN1 binds to an iron-containing molecule recently made famous by the alternative or plant-based "meat" industry: plant heme.

Plant heme is part of a class of chemical compounds called tetrapyrroles, large molecules built from four pentagon rings that tether metal atoms in their center, like iron (heme) or magnesium (chlorophyll). Tetrapyrroles are an ancient class of molecules essential for life in most organisms. Although researchers understand how tetrapyrroles are built, little is known about how they move around the cell and what they do on their journeys.

In a series of experiments using GUN1 isolated from young plant leaves, researchers observed that the protein binds directly to heme and other tetrapyrroles, thereby controlling the cell's production of heme.

"We propose that GUN1 binds to heme to block it from moving from the chloroplast to the nucleus, which may help ensure that chloroplasts develop efficiently," said Masuda

Since GUN1 is degraded in the presence of sunlight, it only releases heme to send a signal to the nucleus while there is light available for the chloroplasts to photosynthesize into energy.

"Understanding how chloroplasts are built naturally may one day allow us to potentially manipulate how plants perform photosynthesis in unfavorable conditions, like under very high- or very low-intensity light," said Masuda.

GUN1 is part of a group of six gene mutations that all affect how the chloroplast and nuclear genomes communicate. The other GUN proteins also interact with other types of tetrapyrrole molecules. Researchers hope that now having characterized all the GUN proteins will lead to a more detailed understanding of how tetrapyrroles contribute to communication from the chloroplast to the nucleus.

"Our next steps will be to pinpoint exactly where along the protein GUN1 binds to heme or other tetrapyrroles, and continue to track heme transport around the cell," said Masuda.

New Haven, Conn. -- A Yale-led collaborative study boosts scientific understanding of how the lung disease idiopathic pulmonary fibrosis (IPF) progresses, providing a roadmap for researchers to discover new treatment targets for the disease.

The study, led by Naftali Kaminski, M.D., the Boehringer-Ingelheim Endowed Professor of Internal Medicine and chief of the Section of Pulmonary, Critical Care, and Sleep Medicine at Yale School of Medicine, and John E. McDonough, instructor and researcher at the medical school, appears in JCI.

In the study, researchers examined differentially affected regions in lungs obtained from individuals with IPF and found that what looks like normal lung is already undergoing changes in specific genes. They then tracked how these genes continue to change, increasing or decreasing, as the disease progresses.

A unique feature of the paper, said Kaminski, is that it provides the first computational model of disease progression in the IPF lung and is accompanied by an interactive website exploring this model. Kaminski believes that the widespread access to the data will accelerate research into new therapies in IPF.

Although Kaminski notes that scientists at Yale and elsewhere have made "substantial scientific progress" on IPF in recent years, there are few treatment options. IPF is a chronic disease in which the lungs become increasingly scarred and unable to function; it affects some 200,000 people in the U.S., with about 30,000 new cases each year. Fifty percent of patients with IPF will die in three to five years following diagnosis, and the cause of IPF is unknown. The two FDA-approved drugs to treat IPF slow the progress of the disease, but do not reverse it. "The drugs may not be pleasant, but they work," said Kaminski, adding that, most importantly, "There's hope on the horizon."

Drug trials for IPF are ongoing, and this latest research, he said, should provide opportunities for researchers to identify new potential drug targets. "My group has felt for years that to develop interventions for IPF that are more effective, we need to understand how the disease progresses in the human lung," Kaminski said.

Animal models for IPF work to show how pulmonary fibrosis impacts the lungs, but not what regulates changes at the genetic level to drive IPF progression in humans. The investigators used a unique system that allowed them to quantify the amount of fibrosis in differentially affected regions in the lung and then to measure the expression of all the genes in the human genome in exactly the same region by RNA sequencing. They also measured microRNAs, small non-coding RNAs known to regulate the expression of genes. They applied advanced systems biology methods to identify tracks of gene expression associated with the progression of IPF in the lung and the molecules that regulate them. Using this approach, they made three key findings. First, they discovered that what looked like normal tissue in the diseased lung was in fact abnormal. Second, they identified gene expression changes that were specific to tissue associated with early, progressive and end-stage fibrosis. Third, they identified distinct molecular regulators for each of these stages.

"This is the first evidence that different stages of the disease may require different interventions," said Kaminski.

He noted that there are thousands of molecules studied and developed by drug companies for other diseases that may also be useful for IPF. "Our data could be run against those databases," he said. "What I would like to do now is accelerate translation. To make this data publicly available for drug repurposing."

An international team of scientists, including three researchers from New Jersey Institute of Technology (NJIT), has shed new light on one of the central mysteries of solar physics: how energy from the Sun is transferred to the star's upper atmosphere, heating it to 1 million degrees Fahrenheit and higher in some regions, temperatures that are vastly hotter than the Sun's surface.

With new images from NJIT's Big Bear Solar Observatory (BBSO), the researchers have revealed in groundbreaking, granular detail what appears to be a likely mechanism - jets of magnetized plasma known as spicules that spurt like geysers from the Sun's upper atmosphere into the corona.

In a paper published in the journal Science, the team describes key features of jet-like spicules that are in solar terms small-scale plasma structures, between 200 and 500 kilometers wide, that erupt continuously across the Sun's expanse. The researchers also, for the first time, show where and how the jets are generated and the paths they travel, at speeds of around 100 kilometers per second in some cases, into the corona.

"Unprecedented high-resolution observations from BBSO's Goode Solar Telescope clearly show that when magnetic fields with opposite polarities reconnect in the Sun's lower atmosphere these jets of plasma are powerfully ejected," said solar physicist Wenda Cao, BBSO's director and an author of the paper.

He added, "This is the first time we've seen direct evidence of how spicules are generated. We have tracked these dynamic features in the H-alpha spectral line down to their foot points, measured the magnetic fields at their foot point, captured the migration of the emerging magnetic elements and verified their interaction with existing magnetic fields of the opposite polarity."

Images captured in the extreme ultraviolet (EUV) spectrum by NASA's Solar Dynamics Observatory spacecraft were used to track the transportation of energy in the corona. These observations showed that it is also common for spicules to be heated to typical coronal temperatures.

Invisible to the human eye except when it appears briefly as a fiery halo of plasma during a solar eclipse, the corona remains a puzzle even to scientists who study it closely. Beginning 1,300 miles from the star's surface and extending millions more in every direction, it is more than a hundred times hotter than lower layers much closer to the fusion reactor at the Sun's core.

Solving what astrophysicists call one of the greatest challenges for solar modeling - determining the physical mechanisms that heat the upper atmosphere - requires high-resolution images that were not available until BBSO's 1.6-meter telescope, the largest operating solar telescope in the world, began capturing images a decade ago.

Scientists at Big Bear have also captured the first high-resolution images, for example, of magnetic fields and plasma flows originating deep below the Sun's surface, tracing the evolution of sunspots and magnetic flux ropes through the chromosphere before their dramatic appearance in the corona as flaring loops.

Cao says it took an international team with diverse expertise and equipment located on Earth and in space to delve this deeply into the Sun's fundamental physics. Cao developed the scientific instruments on Big Bear's telescope and oversaw their operation, while NJIT's Vasyl Yurchyshyn generated the observations, processed the data and advised on its use, and NJIT's Kwangsu Ahn processed the vector magnetic fields data for scientific usage. Tanmoy Samanta and Hui Tian from Peking University in China defined the novel discoveries and wrote the manuscript; they are its first authors.

Artificial muscles will power the soft robots and wearable devices of the future. But more needs to be understood about the underlying mechanics of these powerful structures in order to design and build new devices.

Now, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have uncovered some of the fundamental physical properties of artificial muscle fibers.

"Thin soft filaments that can easily stretch, bend, twist or shear are capable of extreme deformations that lead to knot-like, braid-like or loop-like structures that can store or release energy easily," said L. Mahadevan, the Lola England de Valpine Professor of Applied Mathematics, of Organismic and Evolutionary Biology, and of Physics. "This has been exploited by a number of experimental groups recently to create prototypical artificial muscle fibers. But how the topology, geometry and mechanics of these slender fibers come together during this process was not completely clear. Our study explains the theoretical principles underlying these shape transformations, and sheds light on the underlying design principles."

"Soft fibers are the basic unit of a muscle and could be used in everything from robotics to smart textiles that can respond to stimuli such as heat or humidity," said Nicholas Charles, a PhD student in Applied Mathematics and first author of the paper. "The possibilities are endless, if we can understand the system. Our work explains the complex morphology of soft, strongly stretched and twisted fibers and provides guidelines for the best designs."

The research is published in Physical Review Letters.

Soft fibers, or filaments, can be stretched, sheared, bent or twisted. How these different actions interact to form knots, braids, and helices is important to the design of soft actuators. Imagine stretching and twisting a rubber band as tight as you can. As the twist gets tighter and tighter, part of the band will pop out of the plane and start twisting around itself into a coil or knot. These coils and loops, in the right form, can be harnessed to actuate the knotted fiber.

The researchers found that different levels of stretch and twist result in different types of complex non-planar shapes. They characterized which shapes lead to kinked loops, which to tight coils, and which to a mixture of the two. They found that pre-stretch is important for forming coils, as these shapes are the most stable under stretching, and modeled how such coils can be used to produce mechanical work.

"This research gives us a simple way to predict how soft filaments will respond to twisting and stretching," said Charles.

"Going forward, our work might also be relevant in other situations involving tangled filaments, as in hair curls, polymer dynamics and the dynamics of magnetic field lines in the sun and other stars," said Mahadevan.

You've probably seen a lichen, even if you didn't realize it. If you've ever meandered through the forest and wondered what the crusty stuff on trees or rocks was, they're lichens, a combination of algae and fungi living together almost as if they were one organism. And since they can grow on bare rocks, scientists thought that lichens were some of the first organisms to make their way onto land from the water, changing the planet's atmosphere and paving the way for modern plants. A new study in Geobiology upends this history by delving deep into the DNA of the algae and fungi that form lichens and showing the lichens likely evolved millions of years after plants.

"When we look at modern ecosystems, and we see a bare surface like a rock, oftentimes lichens are the first thing to grow there, and eventually you'll get plants growing on there too," says Matthew Nelsen, lead author of the paper and a research scientist at the Field Museum. "People have thought that maybe that's the way ancient colonization of land worked, but we're seeing that these lichens actually came later in the game than plants."

Four hundred and eighty-five million years ago, Earth was very different from what we see today. Hardly anything lived on land. But lichens can live in extreme conditions. They can grow on bare rocks and break them down, helping to create the soil needed by complex plants with roots (called "vascular plants"). Scientists thought that lichens must have arrived on land before the vascular plants did and made the environment more hospitable. But Nelsen and his colleagues' work calls this timeline into question.

Nelsen didn't set out to disrupt lichen's status as some of the land's first colonizers. He was initially interested in finding out how the algae-fungus relationship that makes up lichens came to be. If lichens could update their relationship status on Facebook, it would definitely be "it's complicated." They're a product of symbiosis, a relationship where two species live together and both benefit. In this instance, the algae--or specialized blue-green algae called cyanobacteria--provide food and the fungi wraps around it creating a shelter. "The question of when lichens evolved and how many times fungi evolved the ability to form symbiotic relationships with algae has been a bit contentious in the past," says Nelsen.

But to accurately determine when lichens evolved, scientists needed to examine the evolutionary history of both the fungi and algae that make them up. The early lichen fossil record isn't very clear; it can be hard to tell lichen fossils apart from other fossils, and all the fossils that scientists know for sure are lichens are younger than the oldest complex plant fossils. So, the researchers used the fossils that were available to extrapolate the ages of family trees of lichen-forming fungi and algae. They compared these family trees with ages of fossil plants. The verdict: lichens probably evolved long after complex plants.

"Lichens aren't as old as we thought they were. They're a younger, newer sort of symbiosis and haven't been around forever, covering the earth long before there were plants and animals running around," says Nelsen.

Unearthing the age of lichens makes it clear that the pattern of modern lichens showing up on rocks before plants doesn't mean that lichens evolved before plants. "It provides a snapshot into what was going on deep in time on Earth, and when some of these groups started appearing," says Nelsen. And since lichens growing on soil can make the ground wetter, hold the soil in place, and influence the kind of nutrients present in soil, learning when lichens arrived on the scene use us a clearer picture of the world in which complex plants evolved.

By understanding what the Earth was like hundreds of millions of years ago, we can examine how it's changed and gain more insight into the current state of our planet. For the researchers, it's similar to the feeling you might get when learning about your family history from an ancestry DNA kit.

"It reshapes our understanding of the early evolution of complex ecosystems on Earth," says Nelsen.

CLEVELAND, Ohio (November 15, 2019)--For some women, sex becomes less satisfying with age, with a pronounced decline during perimenopause. A new study indicates that sexual dysfunction increases by nearly 30% during perimenopause, and vaginal dryness most often has the greatest effect on desire, arousal, lubrication, and overall satisfaction. Study results were published this week in Menopause, the journal of The North American Menopause Society (NAMS).

There are many factors that can negatively affect sexual function, including mental and emotional status, aging, chronic medical problems, and menopause status. Decreasing estrogen levels during the menopause transition cause a variety of biological changes in a woman's body, leading to vaginal atrophy, the thinning, drying, and inflammation of the vaginal walls.

Although previous studies have documented the effect of vaginal atrophy on menopausal women, this new study is one of only a few to assess effect during perimenopause, a transitional time before menopause when the ovaries gradually begin to make less estrogen. It shows that certain symptoms of vaginal atrophy, such as vaginal dryness, are much more prevalent during the menopause transition. Largely as a result of vaginal dryness, researchers noted that sexual satisfaction scores decreased while sexual dysfunction increased by about 30% during the perimenopause years.

Study results appear in the article "Female sexuality and vaginal health across the menopausal age."

"This study examined sexual functioning in women aged 40 to 55 years and identified a link between vaginal dryness and worse sexual function. Given the high prevalence of sexual dysfunction in women, identifying an eminently treatable contributing factor such as vaginal dryness may allow women to maintain their sexual function during the menopause transition," says Dr. Stephanie Faubion, NAMS medical director.

Chaotic mobs of jackdaws suddenly get organised once enough birds join in, new research shows.

The birds form mobs to drive away predators near their nests, and are initially disordered.

But the new study, by biologists at the University of Exeter, physicists at Stanford University and computer scientists from Simon Fraser University in Canada, shows a dramatic switch to "ordered motion" once the group reaches a certain density.

The study also reveals that jackdaws follow different rules when mobbing predators than when flying to winter roosts.

"Traditionally, it is thought that flocking - and other collective behaviour like swarms, fish schools and human crowds - occurs when each individual follows an identical set of rules to every other in the group," said Dr Alex Thornton, of the Centre for Ecology and Conservation on Exeter's Penryn Campus in Cornwall.

"This study shows that these rules are actually flexible.

"When flying to their winter roosts, jackdaws follow what we call 'topological rules' - meaning that they respond to the movements of a fixed number of neighbours, and groups remain ordered regardless of how many birds are flying together.

"When mobbing a predator, however, the jackdaws instead use 'metric rules' where they respond to all the neighbours that are within a given distance. Here, we see order emerging from chaos.

"Jackdaws issue an alarm call to draw other birds to the mob, and at first these groups are completely disordered.

"Then, when the density of birds reaches a certain threshold, it suddenly flips into an ordered, cohesive state where the birds are aligned with their neighbours and move together in an organised way.

"This sudden transition from disorder to order is similar to the phase transitions we see in physics, like when water turns to ice."

This finding that rules of collective behaviour can change in different contexts could have implications for the design of autonomous vehicles, Dr Thornton said.

"Swarms of unmanned aerial vehicles or drones have potential uses in many applications including ecological surveys, fire-fighting and search-and-rescue in remote regions," he said.

"By learning from the behaviour of jackdaws, we can begin to design drones that modify their swarming behaviour to maximise their efficiency in different contexts."

The study used high-speed cameras to film flocks of wild jackdaws at sites in Cornwall, UK, to create 3D reconstructions of the movements of each bird in the flock.

The cells in our body are workshops that continuously operate to produce and process substances to keep us going. When a substance enters a cell for processing, it is surrounded by a portion of the cell's outer membrane to form a sac. The sac then buds off into the cell and becomes a vesicle containing the substance. This ingestion of substances by the cell is called endocytosis. The vesicle is then quickly merged with an endosome, an organelle also frequently referred to as a 'sorting station'. From the endosome, the substance is either recycled back to the cell membrane (for exiting the cell) or forwarded to a lysosome--a cell organelle containing enzymes for the breakdown of substances--for degradation. The substances entering a cell--and thereby an endosome--could be nutrients or signal molecules for processing, or even pathogenic viruses which can cause disease. It is therefore extremely important to fully understand the molecular basis of how endosomes are formed and maintained.

It is generally accepted by scholars in the field that these endosomes are formed and maintained by a mechanism in which vesicles travelling from the cell membrane constantly fuse into them. But in a recent study published in Communications Biology, a group of scientists from Japan and Austria, led by Prof Jiro Toshima from the Tokyo University of Science, claims that vesicles transported out of the Golgi--another crucial cell organelle--and not those from the cell membrane are more important for the formation and maintenance of endosomes. "We used our research to show that endocytic vesicle internalization is not essential, but that vesicle transport from the trans-Golgi network [TGN; the Golgi] is crucial," the team of scientists--comprising Makoto Nagano (Tokyo University of Science), Junko Y. Toshima (Tokyo University of Technology), Daria Elisabeth Siekhaus (Institute of Science and Technology, Austria) and Jiro Toshima--says.

They base their claim on the results of a series of experiments, involving the introduction of mutations or drugs (two drugs called Brefeldin A and Monensin) into yeast cells, to clarify the mechanism of endosome formation. As part of the experiments, they first used mutant yeast strains, which harbor mutations that cause defects in the endocytosis process; that is, they caused the ingestion of substances at the cell membrane to be hampered. Upon observation of the mutated cells, they found that the protein that mediates the formation of endosomes, Rab5, localized at the endosomes as per usual, leading to normal endosome formation.

They then introduced the two drugs into yeast cells to inhibit the transport of specific protein-containing vesicles from the Golgi. By doing so, they expected to find out whether these vesicles are required for the formation and maintenance of endosomes. They saw that smaller amounts of Rab5 localized on the endosomes, hampering endosome formation.

With further similar experiments, Prof Toshima and group saw that certain proteins, which are either resident in the Golgi or recruited to it, are transported from the Golgi to the endosomes where they activate Rab5 and spark the formation of endosomes. Deleting or deactivating the genes crucial to the transport of these proteins from the Golgi ultimately affects endosome formation.

Thus, considering all of these results together, it appears that endocytosis is not necessary for endosome formation and maintenance, but vesicle transport form the Golgi is. "Our results provide a different view of endosome formation and identify the TGN as a critical location for optimal maintenance and functioning of endosomes," Prof Toshima says.

Given that endosomes are essential to the functioning of the cell and, by extension, the organism, understanding the mechanism of its upkeep is important. The results of this compelling study reveal but a fraction of this mechanism and much remains to be discovered. Even so, this advancement in the knowledge of one of the core pathways by which cells process substances in the body can lead to enhanced comprehension of the molecular basis of diseases that involve defective endosomes, thereby leading to better treatments for such diseases.

HERSHEY, Pa. -- When it comes to nicotine delivery, not all electronic cigarettes are created equally, according to Penn State researchers. New research from Penn State College of Medicine shows that JUUL, a popular pod-based electronic cigarette, can deliver more nicotine at a faster rate than most other types of electronic cigarettes that have been studied.

Jessica Yingst, first author and researcher at the College of Medicine, said that previous studies of other electronic cigarettes with high liquid nicotine concentrations revealed that many delivered very little nicotine to the user. The researchers profiled the nicotine delivery capabilities of JUUL, which is known to have a high concentration of nicotine in its pods.

"The JUUL users we studied obtained blood nicotine concentrations almost three times as high as most of the e-cigarette users we previously studied," Yingst said. "JUUL's nicotine delivery is very similar to that of cigarettes."

The researchers published their findings today (Nov. 15), in JAMA Open Network. Six regular JUUL users were asked to puff on their device every 20 seconds for ten minutes for a total of 30 puffs. Blood was collected at intervals during and after vaping. The researchers used liquid chromatography and mass spectrometry to analyze the amount of nicotine in the blood at each time point.

Researchers also asked the participants to rate their withdrawal symptoms and other subjective effects like craving and anxiety both before and after vaping. The participants also completed the Penn State Electronic Cigarette Dependence Index -- a questionnaire designed to measure addiction to electronic cigarettes. JUUL users who completed the survey self-reported higher nicotine dependence compared with more than 3,000 experienced long-term users of other electronic cigarettes. Jonathan Foulds, a co-author of the study and a professor of public health sciences, said that the results obtained from this study with JUUL are different from prior findings that e-cigarettes were less addictive than regular cigarettes.

"In previous studies, we found that e-cigarette users were less addicted than smokers," Foulds said. "However, the high nicotine delivery of the product and the scores on this study suggest that JUUL is probably as addictive as cigarettes."

According to the researchers, the high addiction potential of these e-cigarettes is an important reason why non-smokers should not try them - but they may provide a way for smokers to switch to a less harmful form of nicotine consumption. "In previous work, we determined that JUUL delivered lower levels of some harmful chemicals than cigarettes and even some other e-cigarettes," said John Richie, co-author of the study and professor of public health sciences at the College of Medicine.

Foulds cautioned that products like JUUL pose a dilemma for public health experts.

"This type of product is likely addictive and is attractive to teenagers," Foulds said. "But those same qualities that make it addictive may enable it to help adult smokers switch to a much less harmful form of nicotine consumption."

Bottom Line: This observational study estimated the rate of opioid overdose deaths among Medicare enrollees younger than 65 who qualified for Medicare because of a disability. The study included more than 1.7 million of these enrollees in 2016 and 1,371 opioid overdose deaths. Researchers report those enrollees represented 14.9% of the Medicare population but they accounted for almost 81% of all opioid overdose deaths among all Medicare enrollees. The rate of opioid overdose deaths in this population increased from 57.4 per 100,000 in 2012 to 77.6 per 100,000 in 2016, and was greater among people with psychiatric diseases (such as depression, anxiety and bipolar disorder), substance use disorder (tobacco, alcohol or drug use) and chronic pain. Adults who had all three of these conditions had higher rate of opioid overdose death than those with none of the conditions. Limitations of the study include variations in the quality and accuracy of death certificate data associated with overdose.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Yong-Fang Kuo, Ph.D., of the University of Texas Medical Branch at Galveston, and coauthors.

(doi:10.1001/jamanetworkopen.2019.15638)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

The black holes of Einstein's theory of relativity can be completely described by just three parameters: their mass, spin angular momentum, and electric charge. Since two black holes that share these parameters cannot be distinguished, regardless of how they were made, black holes are said to "have no hair": they have no additional attributes that can be used to tell them apart.

In the early 1970s the late Jacob Bekenstein provided a proof for the nonexistence of hair made of scalar fields given a set of assumptions on the properties of the latter. Researcher Lior Burko of Theiss Research said, "Since Bekenstein's proof, several papers found examples for scalar hair, and all these examples violate one or another of the assumptions made by Bekenstein. But in all cases, the hair was made of the scalar field itself."

Recently, it was shown that black holes that are charged by the maximum possible electric charge ("extreme black holes") can have an additional property, permanent hair that is made of a massless scalar field, and that this newly found hair can be observed from a great distance. "A massless scalar hair does not violate any of the assumptions underlying Bekenstein's proof. It was a big surprise for me when this new hair was found by Angelopoulos, Aretakis, and Gajic, so I wanted to look at it in greater detail. It is hair in a different sense than the kinds of hair that were found before. It is not the scalar field itself, but a certain integral on a derivative of the scalar field that is to be calculated on the surface of the black hole, on its event horizon," said Burko. The new hair can be observed at a great distance, by calculating a different quantity there. "The measurement at a great distance that Angelopoulos, Aretakis, and Gajic found is strictly speaking precise only at infinitely late time," added Burko. "These would be observers who are very distant from the black hole, and who make the measurements in the infinite future. We wanted to see what happens at late but finite times, to see the time dependence of the measurement and how it approaches its asymptotic value. Another special thing about this new hair is that it is applies only for exactly extreme black holes, and we wanted to understand what happens when the black hole is nearly extreme, but not exactly extreme."

Burko and his colleagues Gaurav Khanna of the University of Massachusetts Dartmouth and his former student Subir Sabharwal, currently with the Eastamore Group, showed in a paper just published in Physical Review Research that measurements from a great distance are approaching the hair value, with the difference between them decaying with inverse time. But then they went beyond the original model used by Angelopoulos, Aretakis, and Gajic, and generalized the hair to black holes that rotate at the maximum possible spin rate or just close to it. "In addition to a maximal value of charge, there is also a limit for how fast a black hole can spin. Black holes that spin at the maximal allowed rate are therefore also called extreme black holes. We describe both maximally charged and maximally spinning black holes by the name extreme black holes, as there are many similarities between the two. The new hair was originally found for a very useful toy model for black holes, specifically black holes that are spherically symmetric and electrically charged. But black holes in reality are neither. Instead, we wanted to find out if this hair can be found also for spinning black holes," said Burko. "In the movie Interstellar the monster black hole is nearly extreme. We wanted to see if Gargantua has hair."

The team used very intensive numerical simulations to generate their results. The simulations involved using dozens of the highest-end Nvidia graphics-processing-units (GPUs) with over 5,000 cores each, in parallel. "Each of these GPUs can perform as many as 7 trillion calculations per second; however, even with such computational capacity the simulations took many weeks to complete" said Khanna.

The team showed that for the nearly extreme spinning black holes the hair is a transient behavior. At intermediate times nearly extreme black holes behave like extreme black holes would, but at late times they behave like regular, non-extreme black holes. "Nearly extreme black holes can pretend that they are extreme for only so long. But eventually their non-extremality becomes manifest," Burko summarized. "Nearly extreme black holes that attempt to regrow hair will lose it and become bald again." The team also discusses the observational features, e.g., with gravitational waves observatories such as LIGO/VIRGO or LISA, of the smoking-gun detection of nearly extreme black holes.

For the first time, Australian scientists have shown that environmental DNA (eDNA) can be used to detect the presence of an endangered bird species simply by collecting a cupful of water from the pools where they drink.

eDNA has emerged as powerful tool to trace rare and threatened aquatic species but its application in the detection of threatened terrestrial species is still largely untested. Researchers from Charles Darwin University, The University of Western Australia, and the Northern Territory's Department of Environment and Natural Resources (DENR) have developed a genetic probe that targets and identifies the eDNA of the endangered Gouldian finch (Erythrura gouldiae), a rainbow-coloured grassfinch endemic to the savanna woodlands of northern Australia.

"When it worked in the real world at the waterholes, even where the water was poor quality in places - where it was hot and looked a bit oily - we were really excited" says Professor Karen Gibb of Charles Darwin University, who led the study funded by the Australian Government's National Environmental Science Program.

The eDNA test has the potential to increase our knowledge of the distribution and habitat use of Gouldian finches; essential information to guide land management decisions that will assist the recovery of wild populations.

Gouldian finches were once found in their thousands from the Kimberley region of Western Australia across to Cape York Peninsula in Queensland. The expansion of pastoralism in the first half of the 20th century and changes in the timing and intensity of fires has been linked to the historical decline in the numbers of Gouldian finches, most likely owing to the reduced availability of the grass seeds that form the major part of their diet. Because the finches are found in small groups across the vast, remote and sparsely populated north of Australia, researchers can't always predict where they need to be and when they need to be there to encounter the birds. This makes it difficult to track changes in the numbers of Gouldian finches from year to year.

Yet there is one aspect of their behaviour that researchers can predict: the granivorous Gouldian finches need to drink water each day. As the northern dry season progresses, suitable waterholes become smaller and rarer. The burst of concentrated activity as flocks of finches drink from shrinking waterholes meant they were likely to shed traceable amounts of their DNA into the water.

The researchers developed a two-in-one eDNA test that uses a PCR primer to amplify a fragment of mitochondrial DNA found in estrildid finches and a species-specific probe to detect Gouldian finch DNA. Gouldian finches often drink at waterholes in mixed flocks with masked finches (Poephila personata) and long-tailed finches (P. acuticauda), which are also members of the estrildid family of finches.

"It's a much more accurate test," Professor Gibb says. "By having primers that pick-up other finches it tells us that the eDNA is good enough quality to be amplified. If the Gouldian test is then negative we can be confident that the eDNA test worked, but there just weren't Gouldian finches at that site."

They trialled the eDNA test in aviaries at the Territory Wildlife Park before field trials at the Yinberrie Hills near Katherine. Scientists from the NT Department of Environment and Natural Resources and Indigenous Jawoyn Rangers have been monitoring Gouldian finches at the Yinberrie Hills since 1996, so there was concurrent count data to validate the eDNA results.

The study, published in Endangered Species Research, showed that Gouldian finch eDNA could be reliably detected from a 200 mL water sample collected from waterholes visited by the birds in the previous 48 hours. At waterholes with the highest number of birds, Gouldian finch DNA was still detectable 14 days after sample collection, regardless of whether the sample was stored at room temperature or refrigerated. A more comprehensive field trial, where protocols for sampling, storage and the eDNA test will be refined, is currently underway.

Having a reliable and accurate eDNA test for Gouldian finches means that Indigenous Rangers and other land managers, as well as scientists, could collect water samples as they move across the landscape undertaking other activities.

"People who are travelling around will be able to put a cup of water into an appropriate container and then into a car fridge, and be able to take a lot of samples," Professor Gibb says. "We can cover a much larger area."

Scientists at the University of Birmingham in collaboration with the University of Amsterdam have uncovered a possible explanation for the mental sluggishness that often accompanies illness.

An estimated 12M UK citizens have a chronic medical condition, and many of them report severe mental fatigue that they characterize as 'sluggishness' or 'brain fog'. This condition is often as debilitating as the disease itself.

A team in the University's Centre for Human Brain Health investigated the link between this mental fog and inflammation - the body's response to illness. In a study published in Neuroimage, they show that inflammation appears to have a particular negative impact on the brain's readiness to reach and maintain an alert state.

Dr Ali Mazaheri and Professor Jane Raymond of the University's Centre for Human Brain Health, are the senior authors of the study. Dr Mazaheri says: "Scientists have long suspected a link between inflammation and cognition, but it is very difficult to be clear about the cause and effect. For example, people living with a medical condition or being very overweight might complain of cognitive impairment, but it's hard to tell if that's due to the inflammation associated with these conditions or if there are other reasons."

"Our research has identified a specific critical process within the brain that is clearly affected when inflammation is present."

The study focussed specifically on an area of the brain which is responsible for visual attention. A group of 20 young male volunteers took part and received a salmonella typhoid vaccine that causes temporary inflammation but has few other side effects. They were tested for cognitive responses to simple images on a computer screen a few hours after the injection so that their ability to control attention could be measured. Brain activity was measured while they performed the attention tests.

On a different day, either before or after, they received an injection with water (a placebo) and did the same attention tests. On each test day they were unaware of which injection they had received. Their inflammation state was measured by analysing blood taken on each day.

The tests used in the study assessed three separate attention processes, each involving distinct parts of the brain. These processes are: "alerting" which involves reaching and maintaining an alert state; "orienting" which involves selecting and prioritising useful sensory information; and "executive control" used to resolving what to pay attention to when available information is conflicting.

The results showed that inflammation specifically affected brain activity related to staying alert, while the other attention processes appeared unaffected by inflammation.

"These results show quite clearly that there's a very specific part of the brain network that's affected by inflammation," says Dr Mazaheri. "This could explain 'brain fog'."

Professor Raymond says, "This research finding is major step forward in understanding the links between physical, cognitive, and mental health and tells us that even the mildest of illnesses may reduce alertness."

Dr Leonie Balter the first author of the study which was completed as part of her PhD, concluded : "Getting a better understanding of the relationships between inflammation and brain function will help us investigate other ways to treat some of these conditions. For example, further research might show that patients with conditions associated with chronic inflammation, such as obesity, kidney disease or Alzheimer's, could benefit from taking anti-inflammatory drugs to help preserve or improve cognitive function."

"Furthermore, subtle changes in brain function may be used as an early marker cognitive deterioration in patients with inflammatory diseases."

The next step for the team will be to test the effects of inflammation on other areas of brain function such as memory.