Culture

Irvine, Calif. -- A University of California, Irvine-led study has found that online brain game exercises can enable people in their 70s and even 80s to multitask cognitively as well as individuals 50 years their junior. This is an increasingly valuable skill, given today's daily information onslaught, which can divide attention and be particularly taxing for older adults.

"The brain is not a muscle, but like our bodies, if we work out and train it, we can improve our mental performance," said lead author Mark Steyvers, a UCI professor of cognitive sciences. "We discovered that people in the upper age ranges who completed specific training tasks were able to beef up their brain's ability to switch between tasks in the game at a level similar to untrained 20- and 30-year-olds."

The findings, published in Proceedings of the National Academy of Sciences, underscore the cognitive cost of multitasking, which dilutes function by splitting focus, as well as the ways in which people across the lifespan can overcome the brain drain brought on by both the increasingly cluttered multimedia environment and the natural aging process.

For the study, Steyvers and his colleagues partnered with Lumosity, an online platform that offers a variety of daily brain training games. They focused on data from "Ebb and Flow" - a task-switching game that challenges the brain's ability to shift between cognitive processes interpreting shapes and movement. Of the millions of people who played the game between 2012 and 2017, researchers randomly sampled the performance of about 1,000 users within two categories: those who ranged in age from 21 to 80 and had completed fewer than 60 training sessions; and adults 71 to 80 who had logged at least 1,000 sessions.

They found that the majority of older and highly practiced players were able to match or exceed the performance of younger users who had not played very much. Any lead seniors had, though, significantly declined after the 21- to 30-year-olds had completed more than 10 practice sessions.

"Medical advances and improved lifestyles are allowing us to live longer," Steyvers said. "It's important to factor brain health into that equation. We show that with consistent upkeep, cognitive youth can be retained well into our golden years."

More than three decades of research on Alzheimer's disease have not produced any major treatment advances for those with the disorder, according to a UCLA expert who has studied the biochemistry of the brain and Alzheimer's for nearly 30 years. "Nothing has worked," said Steven Clarke, a distinguished professor of chemistry and biochemistry. "We're ready for new ideas." Now, Clarke and UCLA colleagues have reported new insights that may lead to progress in fighting the devastating disease.

Scientists have known for years that amyloid fibrils -- harmful, elongated, water-tight rope-like structures -- form in the brains of people with Alzheimer's, and likely hold important clues to the disease. UCLA Professor David Eisenberg and an international team of chemists and molecular biologists reported in the journal Nature in 2005 that amyloid fibrils contain proteins that interlock like the teeth of a zipper. The researchers also reported their hypothesis that this dry molecular zipper is in the fibrils that form in Alzheimer's disease, as well as in Parkinson's disease and two dozen other degenerative diseases. Their hypothesis has been supported by recent studies.

Alzheimer's disease, the most common cause of dementia among older adults, is an irreversible, progressive brain disorder that kills brain cells, gradually destroys memory and eventually affects thinking, behavior and the ability to carry out the daily tasks of life. More than 5.5 million Americans, most of whom are over 65, are thought to have dementia caused by Alzheimer's.

The UCLA team reports in the journal Nature Communications that the small protein beta amyloid, also known as a peptide, that plays an important role in Alzheimer's has a normal version that may be less harmful than previously thought and an age-damaged version that is more harmful.

Rebeccah Warmack, who was a UCLA graduate student at the time of the study and is its lead author, discovered that a specific version of age-modified beta amyloid contains a second molecular zipper not previously known to exist. Proteins live in water, but all the water gets pushed out as the fibril is sealed and zipped up. Warmack worked closely with UCLA graduate students David Boyer, Chih-Te Zee and Logan Richards; as well as senior research scientists Michael Sawaya and Duilio Cascio.

What goes wrong with beta amyloid, whose most common forms have 40 or 42 amino acids that are connected like a string of beads on a necklace?

The researchers report that with age, the 23rd amino acid can spontaneously form a kink, similar to one in a garden hose. This kinked form is known as isoAsp23. The normal version does not create the stronger second molecular zipper, but the kinked form does.

"Now we know a second water-free zipper can form, and is extremely difficult to pry apart," Warmack said. "We don't know how to break the zipper."

The normal form of beta amyloid has six water molecules that prevent the formation of a tight zipper, but the kink ejects these water molecules, allowing the zipper to form.

"Rebeccah has shown this kink leads to faster growth of the fibrils that have been linked to Alzheimer's disease," said Clarke, who has conducted research on biochemistry of the brain and Alzheimer's disease since 1990. "This second molecular zipper is double trouble. Once it's zipped, it's zipped, and once the formation of fibrils starts, it looks like you can't stop it. The kinked form initiates a dangerous cascade of events that we believe can result in Alzheimer's disease."

Why does beta amyloid's 23rd amino acid sometimes form this dangerous kink?

Clarke thinks the kinks in this amino acid form throughout our lives, but we have a protein repair enzyme that fixes them.

"As we get older, maybe the repair enzyme misses the repair once or twice," he said. "The repair enzyme might be 99.9% effective, but over 60 years or more, the kinks eventually build up. If not repaired or if degraded in time, the kink can spread to virtually every neuron and can do tremendous damage."

"The good news is that knowing what the problem is, we can think about ways to solve it," he added. "This kinked amino acid is where we want to look."

The research offers clues to pharmaceutical companies, which could develop ways to prevent formation of the kink or get the repair enzyme to work better; or by designing a cap that would prevent fibrils from growing.

Clarke said beta amyloid and a much larger protein tau -- with more than 750 amino acids -- make a devastating one-two punch that forms fibrils and spreads them to many neurons throughout the brain. All humans have both beta amyloid and tau. Researchers say it appears that beta amyloid produces fibrils that can lead to tau aggregates, which can spread the toxicity to other brain cells. However, exactly how beta amyloid and tau work together to kill neurons is not yet known.

In this study, Warmack produced crystals, both the normal and kinked types, in 15 of beta amyloid's amino acids. She used a modified type of cryo-electron microscopy to analyze the crystals. Cryo-electron microscopy, whose development won its creators the 2017 Nobel Prize in chemistry, enables scientists to see large biomolecules in extraordinary detail. Professor Tamir Gonen pioneered the modified microscopy, called microcrystal electron diffraction, which enables scientists to study biomolecules of any size.

AMES, Iowa -- Satisfaction with your home can depend on its size compared to your neighbors' homes, according to new Iowa State University research.

Daniel Kuhlmann, assistant professor of community and regional planning, found that people are more likely to be dissatisfied with their house if it is smaller than their neighbors'. His study was published last week in the academic journal Housing Studies.

This study provides evidence that people care not only about their house's features, but their relative position: how their house compares in size to those of their immediate neighbors.

"Although we may not realize it, our housing decisions may affect our neighbors' actions," Kuhlmann said. "Because housing consumption produces these types of externalities, by building a large house we could unwittingly push our neighbors to spend more money to buy larger homes to catch up."

Kuhlmann says this is one possible explanation for the steady increase in the size of single-family houses in the U.S. over the last 50 years.

"As suburbs become more developed and go through new homebuilding, that can waterfall," he said. "The next person who builds a house would have been totally fine with a 10-bedroom house - but now they think they need a 12-bedroom house to be considered in good standing.

"Large houses tend to beget larger houses."

For this study, Kuhlmann analyzed data from the U.S. Census' 1993 National American Housing Survey, which included a special neighborhood sample of more than 1,000 homes and their 10 nearest neighbors to assess satisfaction. Most housing data tend to focus on either housing units or people, not both. This section of the 1993 survey is rare in that sense, and it's something that likely won't be replicated, Kuhlmann says, due to increased efforts to avoid identification of survey respondents.

Kuhlmann's model shows that those living in the smallest house in their neighborhood are on average 5% more likely to report that they are dissatisfied with their unit than are those living in the largest house.

"The reason I look at size as opposed to other housing characteristics is that size is easy to measure and compare," he said. "If size matters, there are probably a lot of other housing characteristics that matter, too, such as the age of housing stock or an architecturally outdated home - but it's harder to quantify those differences."

Kuhlmann says these results can help scholars and policymakers who want to understand and find solutions to neighborhood-level opposition to new development. A common concern among development opponents is that new housing will alter their neighborhood character, but Kuhlmann's study suggests "that community concerns about neighborhood character may belie more tangible fears about how development will affect their perceptions of their own homes," he wrote in the paper.

This study identifies possibilities for future research: whether these positional housing concerns cause people to move, and how people's frame of reference changes when comparing a new home to their current one.

Why do languages sound so different, when people across the world have roughly the same speech organs (mouth, lips, tongue and jaw)? Does the shape of our vocal tract explain some of the variation in speech sounds? In extreme individual cases, it clearly does: when children are born with a cleft palate, the roof of the mouth is not formed properly, which affects their speech. However, it is unclear whether subtle anatomical differences between normal speakers play a role. Language and speech are also shaped by repeated use and transmission from parents to children. As language is passed on to new generations, small differences may sometimes be amplified. This observation led a team based at the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, to ask "what happens when tiny differences in vocal tract anatomy "meet" cultural transmission?"

The team decided to focus on whether the shape of the hard palate might influence the way vowels were learned, articulated and passed on across generations of artificial agents. Because changing the shape of the hard palate in human participants is ethically and practically problematic, the scientists opted for a computational study, adapting an existing computer model of the vocal tract. The team imported actual hard palate shapes from more than one hundred MRI scans of human participants into the computer model. With machine learning, they trained agents to articulate five common vowels, such as the 'ee' sound in "beet" and the 'oo' sound in "boot". Next, a second generation tried to learn these particular vowels, which were then passed on to the next generation, and so on for fifty generations. "This simulates a simple model of language change and evolution in a computer", explains co-author Rick Janssen, currently machine learning specialist at ALTEN and Philips Research in The Netherlands. Would subtle anatomical differences in palate shape lead to differences in pronunciation? And crucially, would these differences become more pronounced through repeated transmission?

Biology matters

The subtle differences in the shape of the hard palate did influence how accurately the five vowels were articulated. Importantly, the cultural transmission of speech sounds across generations amplified these small differences, even though the agents actively tried to compensate for their hard palate shape by using other articulators (such as the tongue). "Even small variations in the shape of our vocal tract may affect the way we speak, and this may even be amplified - across generations - to the level of differences between dialects and languages. Thus, biology matters!", explains the lead author, Dan Dediu, currently at the Laboratoire Dynamique Du Langage, Université Lumière Lyon 2 in France.

According to the authors, this result may also help us better understand the effects of anatomical variation on speech and how to correct it when desired, for instance in case of speech pathology, forensic linguistics, dentistry and post-surgery recovery. But most importantly, the study highlights the importance of individual variation in speech and language in the context of our universal similarities: Co-author Scott Moisik, currently at the School of Humanities, Nanyang Technological University in Singapore, concludes: "while we are all humans and fundamentally the same, we are also unique individuals, and one can really hear it".

Alcohol consumption is a major cause of chronic liver disease in the United States, and binge drinking is emerging as a significant contributor to liver injury. According to the Centers for Disease Control and Prevention, one in six U.S. adults binge drink four times per month. In a recently published study examining the effects of binge drinking on rats, researchers from the University of Missouri School of Medicine discovered that female rats who were of equal age and weight to male rats were more sensitive to alcohol and experienced alcoholic liver injury at a higher rate than male rats.

"Some chronic drinkers can drink for several years and still live relatively healthy lives," said Shivendra Shukla, PhD, Margaret Proctor Mulligan Professor of medical pharmacology and physiology at the University of Missouri School of Medicine. "But many chronic drinkers are susceptible to liver damage when they binge drink. The liver is the metabolic powerhouse of the body and liver injury can compound damage to other organs. We studied the similarities and differences of gender-specific responses to repeat binge drinking. Our research showed just three binge drinking episodes triggered a response for more injury in the female rats."

Shukla found a statistically significant difference using just four male and four female rats, giving them the same amount of alcohol three times at 12-hour intervals. He collected and analyzed blood and liver tissues four hours after the last binge episode. Shukla discovered the blood alcohol concentration was twice that in the female rats, but not all damage in males and females reflected that ratio. He discovered the female rats had nearly 4 times as much fatty build-up in the liver, a trigger for additional inflammation and damage.

"There's a protein called diacylglycerol kinase-alpha (DGKa) that has been shown in other studies to promote tumor growth and cancer," Shukla said. "In our findings, this protein goes up 20% in male rats, but increases 95% in females. However, any role this protein plays in alcohol-induced breast cancer is unknown and remains to be investigated in the future."

Shukla says additional studies in humans will be needed to further understand the potential differences in how binge drinking affects males and females, and the metabolic causes for these differences.

"Unfortunately, alcohol has been glamorized," Shukla said. "It is dangerous. Don't binge drink. The research is very clear."

In addition to Shukla, the study authors include Ricardo Restrepo, PhD, Annayya Aroor, PhD, Robert Lim, PhD, Ronald Korthuis, PhD, and Xuanyou Liu, graduate student from the Department of Medical Pharmacology and Physiology at the University of Missouri School of Medicine; and David Ford, PhD, and Jacob Frank, graduate student, Department of Biochemistry and Molecular Biology and Center for Cardiovascular Research at Saint Louis University.

The study, "Binge alcohol is more injurious to liver in female than male rats: histopathological, pharmacological, and epigenetic profiles," was recently published in the Journal of Pharmacology and Experimental Therapeutics. The authors of the study declare that they have no conflicts of interest.

CHAMPAIGN, Ill. -- Recognizing a gap in care for law enforcement K-9s injured on the job, a team of veterinarians, emergency medical services experts and canine handlers has developed protocols for emergency medical service personnel who may be called upon to help treat and transport the injured dogs.

The protocols appear in a special report in the medical journal Prehospital and Disaster Medicine.

Law enforcement K-9s face the same dangers their human handlers confront, said Dr. Maureen A. McMichael, a professor of veterinary clinical medicine at the University of Illinois who led the effort to develop the protocols. Dogs on the job are sometimes shot or experience blunt force trauma, smoke inhalation, opioid drug exposure or other potentially life-threatening injuries.

While a few states are beginning to allow EMS personnel to treat and transport law enforcement K-9s to emergency veterinary facilities when those workers are not busy with human patients, little guidance or training is available to help them care for canine patients, said McMichael, who also is on the faculty of the Carle Illinois College of Medicine at the U. of I. The new protocols begin to address this shortfall, she said.

"Emergency medical personnel are well-trained in all aspects of prehospital care, but few are trained to apply their knowledge to canine patients," she said. "Our goal is to help them adapt their training to also serve the needs of law enforcement K-9 patients."

Such training is as important to the health and well-being of the EMS personnel as it is to the dogs, McMichael said. Even the best-trained dogs sometimes bite their handlers or others in moments of distress or confusion. With a maximum bite force of 800 pounds per square inch, the dogs can severely injure anyone nearby.

Some treatments may even enhance the danger. For example, naloxone - which may be administered to counter the dangerous effects of exposure to powerful opioids - can cause unconscious dogs to awaken in a frenzied, aggressive state. For this reason, the protocols recommend that a dog's handler immediately place a basket muzzle on an injured dog before anyone attempts to treat it. A basket muzzle is essential because dogs need to be able to pant with their mouths open to cool off, the authors report. If a handler is not available, the protocols offer guidance on how to safely muzzle a dog.

"Of course, it's strange for emergency medical personnel who normally treat humans to think about things like muzzles and other equipment designed for dogs, or to figure out how to administer drugs or diagnostic tests to dogs," McMichael said. "That's why we suggest they get preliminary training, establish relationships with emergency veterinary clinics, develop a list of facilities and their locations, and have on hand the phone numbers of emergency veterinary contacts they can call in the event of a serious K-9 injury."

The protocols offer guidance on a host of procedures that would not be immediately obvious to someone trained to stabilize, treat and transport human patients: They describe how to take a dog's vital signs, where to make an intramuscular injection, what kinds of analgesics work best in dogs, how to administer drugs intranasally, and how to adapt a human oxygen mask to a dog's snout when necessary. They also recommend that emergency medical staff have on hand a basket muzzle, leash, specially sized catheters, pediatric blood pressure cuffs, tennis balls and rawhide. Toys are good for reducing anxiety in dogs, the authors note.

There is no official record-keeping on the number of law enforcement K-9s that are injured or killed on the job, though some agencies voluntarily report the deaths. Over a period of about 30 months ending in July 2018, there were 68 reported law enforcement K-9s killed on the job in the U.S., McMichael said. Heat stroke took the lives of 21 dogs. Most of the others died from traumatic injuries, including blunt- and penetrating-force trauma, and drowning.

"These dogs risk their lives to protect the public and their human law enforcement handlers," McMichael said. "As more states sponsor legislation to improve their access to critical care, we also need to step up to make sure that the system is prepared to meet their medical needs in their moment of crisis."

WASHINGTON -- If you've ever tried to swat a fly, you know that insects react to movement extremely quickly. A newly created biologically inspired compound eye is helping scientists understand how insects use their compound eyes to sense an object and its trajectory with such speed. The compound eye could also be used with a camera to create 3D location systems for robots, self-driving cars and unmanned aerial vehicles.

In The Optical Society (OSA) journal Optics Letters, researchers from Tianjin University in China report their new bio-inspired compound eye, which not only looks like that of an insect but also works like its natural counterpart. Compound eyes consist of hundreds to thousands of repeating units known as ommatidia that each act as a separate visual receptor.

"Imitating the vision system of insects has led us to believe that they might detect the trajectory of an object based on the light intensity coming from that object rather than using precise images like human vision," said Le Song, a member of the research team. "This motion-detection method requires less information, allowing the insect to quickly react to a threat."

Imitating an insect eye

The researchers used a method known as single point diamond turning to create 169 microlenses on the surface of the compound eye. Each microlens had a radius of about 1 mm, creating a component measuring about 20 mm that could detect objects from a 90-degree field of view. The fields of view of adjacent microlenses overlapped in the same way that ommatidia do for most insects.

One of the challenges in making an artificial compound eye is that image detectors are flat while the surface of the compound eye is curved. Placing a light guide between the curved lens and an image detector allowed the researchers to overcome this challenge while also enabling the component to receive light from different angles uniformly.

"This uniform light receiving ability of our bio-inspired compound eye is more similar to biological compound eyes and better imitates the biological mechanism than previous attempts at replicating a compound eye," explained Song.

To use the artificial compound eye for measuring 3D trajectory, the researchers added grids to each eyelet that help pinpoint location. They then placed LED light sources at known distances and directions from the compound eye and used an algorithm to calculate the 3D location of the LEDs based on the location and intensity of the light.

The researchers found that the compound eye system was able to rapidly provide the 3D location of an object. However, the location accuracy was reduced when the light sources were farther away, which could explain why most insects are nearsighted.

How insects see the world

"This design allowed us to prove that the compound eye could identify an object's location based on its brightness instead of a complex image process," said Song. "This highly sensitive mechanism suits the brain processing ability of insects very well and helps them avoid predators."

According to the researchers, the ability of the new bio-inspired compound eye to detect an object's 3D location could be useful for small robots requiring fast detection from a very lightweight system. It also offers a new way for biologists to study the visual systems of insects.

The researchers are planning to imbed the localization algorithm into platforms such as integrated circuits to allow the system to be incorporated into other devices. They are also developing ways to mass produce the compound eye lenses to reduce the unit cost.

Brain metastases are among the deadliest tumor metastases, with a median survival period of less than one year, and the incidence of brain metastasis is rising.

A new Tel Aviv University study finds that melanoma brain metastasis occurs when tumor cells "hijack" an inflammatory pathway in the brain. Blocking this pathway could prevent these metastases from developing, according to the research.

"The prognosis of patients with brain metastases is very grim," explains Prof. Neta Erez of the Department of Pathology at TAU's Sackler Faculty of Medicine, the lead author of the study. "Patients used to die from metastases in other places before brain metastases were clinically evident. Treatments have improved and patients are living longer, so the incidence of diagnosed brain metastases is increasing. Understanding how and why brain metastasis occurs is an urgent challenge facing cancer researchers today."

The research was published in Cell Reports on August 13. It was conducted by TAU graduate students Dr. Hila Doron and Malak Amer, in collaboration with Prof. Ronit Satchi-Fainaro, also of TAU's Sackler Faculty of Medicine.

The new research focuses on melanoma brain metastasis because "melanoma is the deadliest skin cancer due to its high rate of metastasis, frequently to the brain," says Prof. Erez.

The scientists utilized a mouse model of spontaneous melanoma brain metastasis to study the interactions of melanoma tumors within the brain microenvironment. They discovered that melanoma brain metastasis is facilitated by the takeover of a physiological inflammatory pathway by astrocytes, the brain cells that maintain a protected environment in the brain. In addition, astrocytes respond to tissue damage in the brain by instigating an inflammatory and tissue repair response to contain the damage, secreting inflammatory factors that recruit immune cells.

"We discovered that tumor cells recruit these inflammatory factors to hijack their way to the brain," says Prof. Erez. "We identified a specific factor that mediates their attraction to the brain and showed that brain metastasising melanoma cells express the receptor for the inflammatory factor, which is how they respond to this signal."

Significantly, when the researchers used genetic tools to inhibit the expression of the receptor on melanoma cells, they successfully blocked the ability of tumor cells to respond to astrocyte signalling -- and the development of brain metastases was significantly inhibited.

After the initial research was performed in a pre-clinical mouse model, the scientists validated their results in the brain metastases of patients who had undergone brain surgery, finding that astrocytes express the same inflammatory factor (CXCL10) and that the tumor cells express the same receptor (CXCR3) as the mouse model. This suggests that the identical mechanism is operative in humans.

"Our findings suggest that blocking this signaling pathway may prevent brain metastasis," concludes Prof. Erez. "The CXCL10-CXCR3 axis may be a potential therapeutic target for prevention of melanoma brain metastasis."

The researchers are currently investigating the trigger that instigates inflammation in the brain, which promotes metastasis.

New Rochelle, NY, August 19, 2019-Although the literature describes the mammalian zygote as a totipotent cell, one researcher challenges this view and has proposed a revised alternative model of mammalian cellular totipotency. The basis for this new model and its implications and potential applications are presented in an article published in Stem Cells and Development, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Stem Cells and Development website.

"On Mammalian Totipotency - What Is the Molecular Underpinning for the Totipotency of a Zygote?" is the work of Kejin Hu, PhD, University of Alabama at Birmingham. Dr. Hu explores the concept of a totipotency - the ability of a stem cell to give rise to any cell type or a blastomere to form a complete embryo - from a molecular perspective. He defines three main aspects of totipotency: genetic, epigenetic, and biochemical (the capacity to be reprogrammed to epigenetic totipotency). While a zygote is genetically totipotent, it is not epigenetically totipotent. It does, however, have the capacity for reprogramming to a totipotent state. Based on these conclusions, Dr. Hu developed his revised model for the capacity for cellular totipotency.

"Stem Cells and Development values a continuing and evolving discourse on this fascinating and contentious topic," says Editor-in-Chief Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI.

Research reported in this publication was supported by the National Institutes of Health under Award Number 1R01GM127411. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

BURNS, OREGON, August 19, 2019--Burning invasive western juniper increases the time--post-fire--that native mountain sagebrush will remain the dominant woody vegetation in the plant community by at least 44 percent compared to cutting juniper back, according to a new study in Ecology and Evolution by Agricultural Research Service (ARS) scientists and their collaborators.

It is important to maintain sagebrush as the dominant woody vegetation in sagebrush steppe communities in the northwestern U.S. where western juniper (Juniperus occidentalis Hook) is encroaching on and replacing sagebrush. Among the benefits are providing endangered sage-grouse better long-term habitat. However, as soon as juniper cover reaches 3 percent, sage-grouse stop using the area. In addition, juniper encroachment greatly increases erosion risks, and reduces forage production by 2- to 10-fold, depending on the specific site.

A team of scientists from the ARS Range and Meadow Forage Management Research Laboratory in Burns, Oregon, Oregon State University and The Nature Conservancy compared the results of prescribed burns with areas where cutting down juniper was employed as the control method at 77 sagebrush steppe locations in Southeastern and Southcentral Oregon, Northern California and Southwestern Idaho.

The researchers looked at ecological data for as long as 33 years after either fire or cutting down juniper was used to control junipers.

"Counter to commonly held beliefs, what we found was prescribed burns were a better conservation practice for encouraging long-term sagebrush dominance in areas that had been encroached upon by western juniper compared to mechanically cutting," ARS rangeland scientist Kirk W. Davies said.

Previously, shorter term studies had suggested that cutting was a more effective practice.

"If we need to restore immediate sagebrush dominance in an area that is a mix of juniper and sagebrush, cutting will achieve that," Davies pointed out. "But if we want longer term sagebrush dominance, prescribed burning of encroaching juniper can be a logical choice." Both fire and cutting have critical roles in the conservation of sagebrush communities."

Removing juniper by cutting is significantly more expensive than using prescribed fires. But cutting does not result in any immediate loss of sagebrush and sage-grouse habitat as prescribed burning does.

Evaluating cutting and prescribed burn effects over an extended time not only provided evidence that prescribed burns provided extended juniper control, it also validated the ecological model that had predicted this outcome.

"We wanted to evaluate the effectiveness of cutting versus prescribed burns because we thought we were observing more young juniper trees in areas that had been cut in the last decade or so compared to burned areas," Davies explained.

With this research, federal and state land management agencies and private landowners will be able to make better decisions about selecting control methods.

"In the end, if you burn, in the long run you will have a lot more sagebrush habitat," Davies said.

BROOKLYN, New York, Monday, August 19, 2019 - Researchers at the NYU Tandon School of Engineering have discovered a new way to identify the state of individual cells by bringing principles of mechanical engineering and physics to bear on processes that are now well understood at the macro level, but not yet at the cellular level: how stressors such as injury and disease force an organism into a new level of equilibrium -- a biological process of finding a "new normal" called allostasis. The researchers' findings carry major implications for the diagnosis and staging of chronic diseases like hypertension and diabetes.

The team, led by Weiqiang Chen, assistant professor of mechanical and aerospace engineering and of biomedical engineering, and Vittoria Flamini, industry assistant professor of mechanical and aerospace engineering, used live cell imaging and a novel micro-mechanical tool to apply a transient, local physical stress on cells while simultaneously measuring dynamic allostatic responses and the tension of the cells' cytoskeleton (CSK) and other cellular structures, cellular energies.

The study, "Energy-Mediated Machinery Drives Cellular Mechanical Allostasis," which will be featured in Advanced Materials, details how the team measured mechanical stress and energies of cells and compared the stress patterns to those of cells in patients with chronic conditions like type II diabetes, allowing them to build predictive models for diabetes and other conditions.

To study how the cells "remodeled" themselves through mechanical and energy-related processes in response to external stimuli, the team employed a "tweezer" developed by Chen that uses ultrasound pulses and "microbubbles" that attach to the cell membrane and -- as the pulses perturb the bubbles -- exert mechanical forces on the cells. The team embedded the vascular-muscle test cells in a substrate comprising elastic polydimethylsiloxane (PDMS) micropillars. This setup allowed them to quantify cellular force and energy during the operation by measuring deflections of the micropillar substrate; fluorescent microscopy allowed the team to visually monitor how stress reorganized the CSK, especially its constituents actin and myosin that, like metal fibers in a steel-belted radial tire, can become dysfunctional and deformed under force.

Using experimental results, the team built a new biophysical model of energy-driven cellular machinery for understanding allostasis in cells. In this process, cellular energy not only provides the driving power for adaption but also a negative feedback to help in restabilizing the cell's system.

"A skewed energy pattern and cell maladaptation may indicate a transformation of healthy condition into a pathological contexts, such as diabetes, hypertension, or aging," said Chen.

The researchers tested their model on four presentations of CSK tension, actin and myosin, and net energy, before, during and after the introduction into cells of chemical agents that generate specific dysfunctional cellular patterns that are phenotypes for disease: For example, disruption in such cell CSK structures as actin fibers can result in a weak adaptative process which may reveal pathological condition like diabetes, while over-activity in actin polymerization in cells may cause "prolonged excitation" or "hypo-reactivity" without an "off" time after a perturbation in conditions like hypertension.

"Energy balance is a proxy for health," said Flamini. "Energy and physics are involved in cellular behaviors; proof of concept is how the energy pattern looks for different conditions. We have shown we can predict that."

"The ability to achieve stability through change is a critical biological adaptation allowing living organisms to stabilize internal and external environment changes," she explained. "However, it remains unclear how it happens in a single cell. Our research addressed this question for a single cell system in which energy plays a key role in the process."

Added Weiqiang, "In collaboration with colleagues at NYU Langone Health, the team is focusing on cardiovascular diseases because they are directly related to mechanical behaviors of vascular cells. In an aneurysm, for example, inflammation affects proteins that regulate the elasticity of vascular cells. We are now looking at mechanical force in development of diseases like this."

A forthcoming paper will look at the potential of this research to expedite disease diagnosis and disease staging in aneurysm.

What The Study Did: An analysis of combined patient-level data from two randomized clinical trials  examined outcomes of dual antiplatelet therapy with clopidogrel and aspirin after minor stroke or transient ischemic attack.

Authors: S. Claiborne Johnston, M.D., Ph.D., of the University of Texas at Austin, is the corresponding author.

(doi:10.1001/jamaneurol.2019.2531)

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.

New research from the University of Warwick has pioneered an economic perspective on controlling livestock diseases. Focusing on Foot and Mouth Disease (FMD), bovine TB (bTB) and bluetongue virus (BTV), the researchers draw striking conclusions about the role of movement bans in controlling an outbreak.

In the 2001 outbreak of FMD, the movement of cattle, sheep and other livestock was generally banned in an effort to prevent the spread of infection. Similarly in 2007, an outbreak of bluetongue virus lead to large-scale movement bans across eastern England.

Given that the livestock industry relies on the movement of animals (between farms or farm to slaughter) to make a profit, such movement bans can have a profound and wide ranging impact on farmers. Moreover, in 2001 the general message that "the countryside is closed" resulted in enormous losses to the tourist industry.

The research, "The Role of Movement Restrictions in Limiting the Economic Impact of livestock Infections" and published today (19 August 2019) by Nature Sustainability, found that the current UK government policy of national movement bans when an outbreak FMD is detected (and large-radius bans for BTV) may cause unnecessary economic harm, when a more localised movement ban could be as successful in halting the spread of the disease and would limit the subsequent negative economic impact.

Led by Dr Mike Tildesley, of Warwick's Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research (SBIDER), the researchers use state of the art predictive models to examine the consequences of different control options.

The researchers argue that whilst livestock movements bring the risk of long-range spread of infection, this risk is strongest from farms in close proximity to where infections has been detected; therefore a limited movement ban (only preventing movements from farms near to known cases) brings most of the benefits but less of the economic costs.

By not automatically implemented national bans during FMD or BTV outbreaks, geographical regions unaffected by the outbreak would not face the same economic impact caused by the restrictions put in place by a national ban.

Accordingly, whilst a national ban on livestock movement was an appropriate initial response to the FMD outbreak of 2001 given its widely dispersed nature, the policy caused potentially avoidable economic harm in the outbreak of 2007.

Commenting on the research Dr Tildesley says:

"Our research says that movement controls need to be carefully matched to both the epidemiological and economic consequences of the disease, and optimal movement bans are often far shorter than existing policy.

"For example, our work suggests that movement bans of between 15-60km are optimal for FMD (with larger radii preferable if tourism losses can be ignored), while for BTV the optimal policy is to allow all movements"

"Adopting these optimal movement bans could lead to vast savings compared to more stringent policies. We fully recognise the need for the government to rapidly contain novel outbreaks in the face of uncertainty, but our work suggests that optimal movement bans should be enacted as soon as possible."

The researchers also looked at bovine tuberculosis (bTB), concluding that the economic cost of any movement ban is more than the epidemiological benefits; however if tests are sufficiently cheap a localised testing program around infected farms could be economically viable in the long-term.

(BOSTON) -- To better understand how tissues and organs develop, fail to function, and regenerate over time, researchers would like to visualize their constituent cells' repertoires of molecules within 3D space. Ambitious efforts like the "Human BioMolecular Atlas Program", the "Human Cell Atlas Project", and several brain atlas projects are underway to map the presence and abundance of many proteins - the products of gene expression - in organs and tissues of the human body at the scale of single cells. However, existing imaging methods are typically limited in various aspects of their performance, their accessibility to researchers, or both.

As reported in Nature Biotechnology, a team led by Peng Yin, Ph.D., at Harvard's Wyss Institute for Biological Engineering and Harvard Medical School (HMS) has now filled this void with a new DNA-nanotechnology-based approach called Immuno-SABER, short for "Immunostaining with Signal Amplification By Exchange Reaction." The method combines the protein targeting specificity of commonly available antibodies with a DNA-based signal-amplification strategy that enables the highly multiplexed visualization of many proteins in the same sample with pre-programmable and tunable fluorescence signals at each target site. The team has validated their method in a broad range of cell and tissue preparations.

"We demonstrated that Immuno-SABER provides the capability to independently tune the signal intensity for individual protein targets 5 to 180-fold, with multiplexing capability to allow the simultaneous detection of many proteins. Together with its speed, relative ease of use and low costs, this technique has the potential to fast-forward ongoing large-scale protein-mapping studies and biomarker discovery efforts across many tissues and diseases," said Peng Yin who is a Wyss Institute Core Faculty member.

Based on his group's advances in harnessing DNA nanotechnology-driven barcoding and signal amplification technologies, Yin recently was recently also selected as an awardee of the Human BioMolecular Atlas Program (HuBMAP) and an awardee of the Human Cell Atlas Project. He also is co-leader of the Wyss Institute's Molecular Robotics Initiative, and Professor of Systems Biology at HMS.

Antibodies are the most common detection reagents for proteins both in research and clinical settings. They are typically tagged with fluorescent stains to make them detectable by microscopy. However, conventional antibody staining methods typically allow only a maximum of five different stains to be used simultaneously, and target proteins can differ significantly in their abundances, making it difficult to distinguish rare protein targets with high sensitivity from the background fluorescence that many tissues display.

Immuno-SABER utilizes the "Primer Exchange Reaction" (PER) method previously reported by Yin's group to synthesize long concatemers of short DNA primer sequences with the help of a catalytic DNA hairpin structure. The PER-generated concatemers are attached via short handle sequences to DNA-barcodes on antibodies that bind to target proteins in fixed cell and tissue samples with high specificity. At the target site, SABER concatemers provide a scaffold with multiple binding sites for complementary fluorescent oligonucleotides ("imagers"), and thus a means to amplify the signal emanating from each protein target.

"By barcoding antibodies with unique short DNA sequences and applying Immuno-SABER, we can simultaneously visualize multiple protein targets on the same sample and with high specificity. This essentially opens up a way to analyze the protein variety present in tissues in a robust and multiplexed fashion," said co-first and co-corresponding author Sinem Saka, Ph.D., who works as a Postdoctoral Fellow on Yin's team.

The team significantly boosted the multiplexing potential of their Immuno-SABER approach by coupling it with their previously developed "DNA-Exchange" technique. In DNA-Exchange, imagers that mark one set of target proteins are washed off and replaced by another set of imagers marking a different group of target proteins and this can be repeated multiple times.

Previously developed methods for highly multiplexed protein detection that work by repeating some of their key steps at different protein targets tend to suffer from suboptimal sensitivities, or take considerable time (low throughput) and finesse to execute. "Exchange-SABER" provides high sensitivity with one single step of staining and amplification, and high multiplexing and throughput with multiple fast imager exchange steps," said co-first author Yu Wang, who is a graduate student on Yin's team. "As proof-of-concept, we visualized 10 different proteins in cryosections of the mouse retina."

Wang was co-mentored by co-author George Church, Ph.D., who is a Core Faculty member at the Wyss Institute and Professor of Genetics at HMS and of Health Sciences and Technology at Harvard University and the Massachusetts Institute of Technology (MIT).

Another key facet of Immuno-SABER facilitating the parallel detection of many proteins at a time is its ability to tune signal strength. The team achieved this by assembling more complex branched structures from PER-generated concatemers that contain higher numbers of binding sites for fluorescent imagers. "Programming the complexity of PER-based concatemer structures allows us to tune the signal strength to the abundance of particular proteins. We can at the same time visualize rare proteins with branched SABER products that enable higher signal amplification, and abundant proteins with linear SABER products," said Saka. In their study, the team combined linear and branched SABER concatemers to, for example, simultaneously visualize six protein targets with different abundances and cellular locations in human tonsil samples.

Yin's team's existing suite of DNA nanotechnology-powered imaging technologies including DNA-PAINT and Discrete Molecular Imaging, have advanced the field of super-resolution microscopy, which allows researchers to study single molecules at their normal locations. To achieve similarly high resolution of proteins in more complex tissue environments the team combined Immuno-SABER with a method known as "Expansion Microscopy", which was previously developed by co-author Edward Boyden, Ph.D., the Y. Eva Tan Professor in Neurotechnology at MIT. The expansion method swells fixed tissues artificially to larger volumes, which increases the separation distance between individual molecules and thus improves their effective resolution without the need for specialized instruments. "Combining Expansion Microscopy with Exchange-SABER simultaneously gives us the high-multiplexing, -throughput, and -resolution capabilities needed to move efforts such as building molecular atlases for the human body more effectively forward," said Wang.

"Peng Yin's team again demonstrates how they can program engineered DNA molecules to carry out specific tasks like molecular robots, in this case allowing us to visualize simultaneously the location of numerous proteins within human cells and tissues with high resolution, which should greatly accelerate discovery of molecular mechanisms of biological control as well as new disease biomarkers," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS, the Vascular Biology Program at Boston Children's Hospital, and Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences (SEAS).

Researchers at McMaster University who rush in after storms to study the behaviour of spiders have found that extreme weather events such as tropical cyclones may have an evolutionary impact on populations living in storm-prone regions, where aggressive spiders have the best odds of survival.

Raging winds can demolish trees, defoliate entire canopies and scatter debris across forest floors, radically altering the habitats and reshaping the selective pressures on many organisms, suggests a new study published today in the journal Nature Ecology & Evolution.

"It is tremendously important to understand the environmental impacts of these 'black swan' weather events on evolution and natural selection," says lead author Jonathan Pruitt, an evolutionary biologist and Canada 150 Chair in McMaster's Department of Psychology, Neuroscience & Behaviour.

"As sea levels rise, the incidence of tropical storms will only increase. Now more than ever we need to contend with what the ecological and evolutionary impacts of these storms will be for non-human animals," he says.

Pruitt and his team examined female colonies of the spider known as Anelosimus studiosus, which lives along the Gulf and Atlantic coasts of the United States and Mexico, directly in the path of tropical cyclones that form in the Atlantic basin from May to November.

To conduct the research, scientists had to tackle many logistical and methodological challenges which included anticipating the trajectory of the tropical cyclones. Once a storm's path was determined, they sampled populations before landfall, then returned to the sites within 48 hours.

They sampled 240 colonies throughout the storm-prone coastal regions, and compared them to control sites, with particular interest in determining if extreme weather--in this case areas disturbed in 2018 by subtropical storm Alberto, Hurricane Florence and Hurricane Michael--caused particular spider traits to prevail over others.

As a species, A. studiosus is divided into two sets of inherited personality traits: docile and aggressive. The aggressiveness of a colony is determined by the speed and number of attackers that respond to prey, the tendency to cannibalize males and eggs, the vulnerability to infiltration by predatory foreign spiders, among other characteristics.

Aggressive colonies, for example, are better at acquiring resources when scarce but are also more prone to infighting when deprived of food for long periods of time or when colonies become overheated.

"Tropical cyclones likely impact both of these stressors by altering the numbers of flying prey and increasing sun exposure from a more open canopy layer," explains Pruitt. "Aggressiveness is passed down through generations in these colonies, from parent to daughter, and is a major factor in their survival and ability to reproduce."

The analysis suggested that after a tropical cyclone event, colonies with more aggressive foraging responses produced more egg cases and had more spiderlings survive into early winter. The trend was consistent across multiple storms that varied in size, duration and intensity, suggesting the effects are robust evolutionary responses, says Pruitt.