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Alzheimer's & Dementia: The Journal of the Alzheimer's Association August 2019 issue

image: This is the Alzheimer's & Dementia August 2019 issue cover

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<i>Alzheimer's & Dementia: The Journal of the Alzheimer's Association</i>

CHICAGO - The August issue of Alzheimer's & Dementia: The Journal of the Alzheimer's Association includes a new perspective from the National Institute on Aging on "paradoxical lucidity," or moments of stunning clarity, in dementia. The commentary is in response to a previously published online paper that is also included in the print issue of the journal and explores the phenomenon of unexpected cognitive lucidity and communication in patients with severe dementias, especially near the time of death.

Paradoxical Lucidity: A Potential Paradigm Shift for the Neurobiology and Treatment of Severe Dementias

Lucidity in Dementia: A Perspective from the NIA

Other articles in the August issue:

Older adults in Japan who lost their homes and were forced to relocate after the 2011 earthquake and tsunami had an associated significantly higher risk of cognitive disability even several years after the disasters, according to research from the University of Hong Kong.

Persistent Impact of Housing Loss on Cognitive Decline After the 2011 Great East Japan Earthquake & Tsunami: Evidence from a 6-year Longitudinal Study

Excessive napping might be a useful early marker of cognitive impairment in the elderly, according to research from the University of California San Francisco. Older men with longer cumulative daily napping had greater cognitive decline and were more likely to develop cognitive impairment over 12 years.

Objective Napping, Cognitive Decline and Risk of Cognitive Impairment in Older Men

Researchers with the Italian Longitudinal Study on Aging Working Group at the University of Bari Aldo Moro evaluated the effect of frailty - or the elevated risk of catastrophic declines in health in older adults - and the risk of developing dementia. The researchers used a model that includes physical, psychological and social aspects of individuals who were cognitively normal when the study started. The model was a short- and long-term predictor of who would develop dementia over time, particularly vascular dementia, by looking at lifestyle factors, social isolation, loneliness and decision-making ability.

Biopsychosocial Frailty and the Risk of Incident Dementia: The Italian Longitudinal Study on Aging

The entire August issue of Alzheimer's & Dementia: The Journal of the Alzheimer's Association can be found at this link.

Special articles on "Super Agers" published by Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM), an open access peer-reviewed journal from the Alzheimer's Association:

What's the secret to being a super ager? An evaluation of data from 172 super agers by researchers in Australia indicates it may be reaching old age without elevated beta amyloid deposits on the brain. Read the paper and accompanying commentaries here.

About the Alzheimer's Association:

The Alzheimer's Association is the world's leading voluntary health organization in Alzheimer's care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research; to provide and enhance care and support for all affected; and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. For more information, visit http://www.alz.org.

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Alzheimer's Association

Europe warming faster than expected due to climate change

image: This is a satellite image of the heat energy emitted from Europe during 25 July 2019 shows this summer's highest extremes.

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Copernicus Sentinel data (2019) ESA - Copernicus Sentinel data (2019)

WASHINGTON - Climate change is increasing the number of days of extreme heat and decreasing the number of days of extreme cold in Europe, posing a risk for residents in the coming decades, according to a new study.

Temperatures in Europe have hit record highs this summer, passing 46.0 degrees Celsius (114.8 degrees Fahrenheit) in southern France. New research in the AGU journal Geophysical Research Letters finds the number of summer days with extreme heat has tripled since 1950 and summers have become hotter overall, while the number of winter days with extreme cold decreased in frequency by at least half and winters have become warmer overall.

The new study finds parts of Europe are warming faster than climate models project.

"Even at this regional scale over Europe, we can see that these trends are much larger than what we would expect from natural variability. That's really a signal from climate change," said Ruth Lorenz, a climate scientist at the Swiss Federal Institute of Technology in Zurich, Switzerland, and lead author of the new study.

Extreme heat is dangerous because it stresses the human body, potentially leading to heat exhaustion or heat stroke. Scientists knew climate change was warming Europe, but they mostly studied long-term changes in extreme temperatures. The new study looked at observational data to evaluate whether the climate models used for regional projections can reproduce observed trends.

In the new study, Lorenz and her colleagues used observational data taken by European weather stations from 1950-2018 and then analyzed the top 1% of the hottest heat extremes and highest humidity extremes, and the top 1% coldest days during that period.

"We looked further at the hottest day or coldest night per year, so for each year we looked for the maximum/minimum value and how these changed over time," Lorenz said.

They found the number of extreme heat days in Europe has tripled since 1950, while the number of extreme cold days decreased by factors of two or three depending on the region. Extremely hot days have become hotter by an average of 2.30 degrees Celsius (4.14 degrees Fahrenheit), while extremely cold days have warmed by 3.0 degrees Celsius (5.4 degrees Fahrenheit) on average. The hottest days and coldest nights warmed significantly more than their corresponding summer and winter mean temperatures.

Individual regions throughout Europe experienced drastically different temperature trends, which makes it difficult to compare the average European temperatures to specific stations' extremes, according to the authors. In Central Europe, the extremes warmed by 0.14 degrees Celsius (0.25 degrees Fahrenheit) per decade more than the summer mean, equivalent to an almost 1.0 degree Celsius (1.8 degree Fahrenheit) increase more than the average over the whole study period, according to Lorenz.

More than 90% of the weather stations studied showed the climate was warming, a percentage too high to purely be from natural climate variability, according to the researchers.

The results also showed that the region was warming faster than climate models projected. Some regions experienced higher extremes than expected and some had lower extremes that expected.

"In the Netherlands, Belgium, France, the model trends are about two times lower than the observed trends," said Geert Jan van Oldenborgh, a climate analysist at the Royal Netherlands Meteorological Institute in De Bilt, Netherlands, who was not connected to the new study. "We're reaching new records faster than you'd expect."

European summers and winters will only grow hotter in the coming years as climate change accelerates, impacting cities and people unprepared for rising temperatures, according to the study authors.

"Lots of people don't have air conditioning for instance and it makes this really important," Lorenz said. "We expected results based on modeling studies but it's the first time we see it in what we've observed so far."

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American Geophysical Union

Unusual mucous-like substance found buried within seafloor sediment

image: This is a biofilm found hidden in the crevice of Arctic seafloor sediment, an unusual location.

Image: 
Friederike Gründger

When Friederike Gründger and her team cracked open the long, heavy cylinders of black sediment drawn from the ocean floor, they were surprised to find pockets of yellowish-green slime buried within two of the samples. The average person may not consider the appearance of such unseemly goo as a cause for celebration, but the biologists knew that this slime, otherwise known as biofilm, was a highly unusual find in this particular location, and could even play a role in terms of climate change.

This group from the Centre for Arctic Gas Hydrates, Environment, and Climate (CAGE) at UiT The Arctic University of Norway set out to investigate the microscopic and macroscopic organisms living in or around cold seep sites such as Gas Hydrate Pingos (GHP) in the Svalbard area.

These dome-like, geological structures leak methane gas into the ocean water with the potential to travel to the surface and enter our atmosphere, possibly advancing climate change.

Underwater organisms thrive on deadly greenhouse gas

Some of the organisms living at these sites are relevant to this process, as they have adapted to live off the methane and convert it into harmless compounds such as carbonate and water. This activity is called anaerobic oxidation of methane (AOM) and has a global impact on the diffusion of underwater methane. The most relevant entities contributing to this process are methanotrophic archaea (ANME -1, -2, and -3) and sulphate-reducing bacteria (SRB), two microorganisms usually found living co-dependently in colonies. It is still unclear, however, where they can be reliably found and how involved they are in such methane control.

Slimy biofilm coats microbial communities; provides protection

Biofilms are glue-like substances that encase clusters of microbes to provide extra protection against the elements. They can be found all throughout nature, even on the human body; biofilms can lead to complications in wound care and adhere to your teeth as plaque. But they are also found on the ocean floor, protecting the microbial communities that set up shop near areas of methane accumulation. Where they are not usually found, however, is within the cracks and crevices of seabed sediment - at least, not as far as we know. But Gründger et al.'s research may be showing us once again how the ocean is constantly capable of surprising us.

Research findings surprise scientists

Here are the highlights from the recently published article from Gründger et. al. in Scientific Reports:

This is the first case of biofilms, visible to the naked eye, found in the cracks of methane-rich sediment in Arctic waters. It could prove to be a common occurrence of which we were previously unaware.

Both biofilm samples found were shown to have a very unique microbial composition with ANME-1 as the dominating group. This has only been seen once before, as reef-forming microbial mats in the Black Sea.

Although ANME-1 and SRB microbes usually help one another to absorb methane, there was no direct cell-to-cell contact between the two in these particular biofilms. This leads our scientists to wonder if ANME-1 could filter the methane without the presence of the SRB, something previously thought impossible.

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UiT The Arctic University of Norway

High-protein bedtime snacks no problem for active women

image: In a study of women weight lifters, nutrition scientists at FSU showed that protein consumption before bed compared to protein consumption during the day does not disturb overnight belly fat metabolism or whole-body fat burn.

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Ashlee Barrett/Florida State University

TALLAHASSEE, Fla. -- Physically active women who have foresworn bedtime snacks should feel no fear cracking open the cupboards after sundown for a protein-rich treat, according to new Florida State University-led research.

In a study of women weight lifters, nutrition scientists at FSU showed that protein consumption before bed compared to protein consumption during the day does not disturb overnight belly fat metabolism or whole-body fat burn.

The findings, published in the Journal of Nutrition, challenge widespread misconceptions about the relationship between nighttime eating, weight gain and metabolism, especially in women.

"For far too long, people have been led to believe that eating before bed causes metabolic disturbances and will make them gain fat," said study author Michael Ormsbee, an associate professor in the College of Human Sciences and the associate director of the FSU Institute of Sports Sciences & Medicine. "However, the data simply does not support this when the food we choose to eat before bed is protein-based and small in size."

While past research has uncovered substantial benefits of nighttime protein consumption, most existing work on the topic focuses exclusively on men. In this study, Ormsbee and his team used two experimental conditions to investigate fat metabolism in a sample of women weight trainers.

In one condition, the study participants drank a casein protein shake 30 minutes after a workout and a taste-matched placebo shake 30 minutes before bed. In the other condition, the participants drank the shakes in the reverse order.

"We wanted to investigate how drinking a protein shake before bed influenced overnight metabolism of fat in fit women as compared to taking that protein shake at another time of day," Ormsbee said.

Researchers then deployed a strategic measurement approach designed to comprehensively assess the full, multistep process of overnight fat metabolism. First, they documented participants' lipolysis -- or fat release from fat cells -- in order to determine whether the timing of protein consumption was linked to cells' ability to unleash stored fat into surrounding tissue.

Then, the team used breath sample measurements to evaluate participants' fat oxidation, or their bodies' capacity to burn the fat released as energy in the muscles.

Scientists have long known that protein consumption paired with exercise can help trigger the release of fat by cells, said study co-author and former FSU doctoral student Brittany Allman, who wrote her dissertation on this study. She and her partners were eager to identify whether, in an active resistance training population, there were any additive effects of protein consumption before bedtime -- a window of accelerated fat release.

The team's measurements revealed that, for women who lift weights, the well-known benefits of a nighttime, high-protein snack far outweigh the costs.

"In women who weight train, there are no differences in overnight local belly fat metabolism or whole-body fat burn whether you eat protein in the form of a protein shake during the day post-workout or at night presleep," said Allman, now a postdoctoral fellow at the University of Arkansas for Medical Sciences and the Arkansas Children's Nutrition Center. "So, essentially, you can eat protein before bed and not disturb fat metabolism."

Allman said she hopes this study and subsequent follow-up investigations will help demystify the science of women's nighttime eating and clear away harmful, unfounded beliefs.

"There are such bad misconceptions about eating at night, that it will 'make me gain weight' or 'slow my metabolism,'" she said. "The research suggests that really only holds true if you're eating a ton of calories and they are carbohydrate- and/or fat-laden. There are so many potential beneficial effects of eating protein at night, and it will be extremely important to take all of this science to the community to try to change the outlook of these dietary habits."

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Florida State University

Isotopes in poop show where secretive jaguars hunt

image: UC associate professor Brooke Crowley holds up a jaguar scat sample in her lab.

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Jay Yocis/UC Creative Services

How do you follow a predator so elusive that its nickname is "shadow cat"?

To track secretive jaguars in the forested mountains of Belize, the University of Cincinnati turned to geology and poop.

Brooke Crowley, a UC associate professor of geology and anthropology, can trace the wanderings of animals using isotopes of strontium found in their bones or the bones of animals they have eaten. This method works even with long-dead animals such as ancient mammoths.

Now she and her research partners are applying the technique to jaguar poop, or scat, found in the geologically diverse Mountain Pine Ridge Forest Reserve in Belize.

Claudia Wultsch, a wildlife biologist from the American Museum of Natural History and City University of New York, and Marcella J. Kelly, a professor of wildlife conservation at Virginia Tech, co-authored the study. Both have studied jaguars in Belize for more than a decade.

The research found that jaguar scat provides isotopic signatures similar to those found in the undigested bones of prey to track the big cat's movements across its varied landscape. Researchers examined strontium, carbon and nitrogen isotopes to identify the habitat and geology of prey upon which the jaguars were feeding.

The isotopes get absorbed in the food chain starting with plants that draw in minerals. Strontium then gets absorbed into the tissues and bones of herbivores that eat the plants and finally those of the predators that hunt them.

Strontium can be coupled with carbon isotopes, which reflect the type of vegetation in which an animal resides such as dense forest compared to open grasslands. This combination is particularly powerful for distinguishing where the cats hunt.?

"The Mountain Pine Ridge Forest Reserve is ideally suited for this kind of study because it has diverse geology and vegetation," Crowley said.

The findings suggest that an isotopic analysis of scat can be a powerful research tool for wildlife conservation and management. The study was published in August in the journal Isotopes in Environmental and Health Studies.

Jaguars are the largest big cat in the Western Hemisphere. Like leopards, they have a camouflaged coat with a unique pattern of spots and rosettes. They are opportunistic hunters, catching small birds and rodents or far bigger prey such as caimans, a type of crocodile.

The cats have disappeared from more than 40 percent of their historic range and are red-listed as near-threatened with extinction by the International Union for Conservation of Nature. They are wide-ranging and wary, which makes them difficult to study in the wild.

"You have to be extremely lucky to see one in the wild," Wultsch said.

In this part of Central America, the jaguar's stronghold is la Selva Maya, or the Mayan Forest, which covers parts of Belize, northern Guatemala and southeastern Mexico. 

"It represents one of the largest blocks of contiguous forest left in Mesoamerica and is critical for jaguar conservation," Wultsch said. 

Even this region has become increasingly fragmented by development over the last 50 years.

"One of the main objectives of our research is to assess how jaguars and other wild cats are doing," Wultsch said.

Researchers have studied jaguars without capturing or handling the animals by setting up remote camera traps and collecting their scat. But isotopic profiling expands the tool box of noninvasive wildlife survey methods, offering a wealth of information from a single scat sample.

The UC study also suggested that jaguars in the reserve were not eating grazing animals such as livestock from area farms.

"Being able to document that isn't happening is reassuring. They're not competing for resources with people in the area," UC's Crowley said.

Finding animal droppings in thick rainforest is not easy, so researchers enlist the help of four-legged field assistants. Wultsch's specially trained dogs have little trouble sniffing out the pungent droppings. The dogs also help researchers collect scat from other wild cats such as pumas, ocelots, margays and jaguarundis that inhabit the reserve.

"We were able to collect tons of poop -- more than 1,000 feline samples," she said.

Wultsch extracted DNA from the samples for a countrywide genetic study of jaguars and other wild cats. She found that despite some habitat fragmentation from human encroachment, jaguars in Belize were maintaining moderate to high genetic diversity. And while jaguars move across most landscapes of Belize, their movement in some protected but geographically isolated areas was limited, the study found. 

The isotope study gives exciting new insights into the ecology of elusive jaguars, Wultsch said. 

"Jaguars face habitat loss and fragmentations across most of their range," she said. "Noninvasive monitoring of jaguars using a multidisciplinary approach of isotopes, genetics and camera traps will help us understand how they are responding to environmental change and different human pressures."

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University of Cincinnati

Fresh water found in the Norwegian Sea

video: The Lofoten islands are visited by millions of people each year. We made a different kind of journey to the famous archipelago, looking not for mountains and beaches. But for the stuff of life itself.

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Maja Sojtaric/CAGE

When we the found fresh water leaking from the seabed, we were very surprised,' explains scientist and marine geologist Wei-Li Hong at the Geological Survey of Norway (NGU).

A remote-controlled vehicle, deployed from research vessel G.O. Sars, collected and measured the water during an expedition in 2017. The leakage likely originated from a large pocket of fresh water, otherwise known as an aquifer, hidden beneath the sediment of the seabed.

Remnants of the last Ice Age

'Fisherman in Nordland county have told us that they also found fresh water in the sea, so pure that it could even be used for coffee. This was in Nordbreigrunnen, a few kilometers outside the town of Meløy,' Hong claims.

This phenomenon probably began during the last Ice Age. The thick ice caps that enveloped Norway pushed down on the crust of the Earth with tremendous force, squeezing large amounts of meltwater down through cracks in the seabed.

'This is a geological process that began millions of years ago when the water became trapped under the sediment. Only now is it finding its way through the cracks and faults again,' Hong says.

The water was found around a kilometer below the seabed, but the aquifer itself could be deeper, and scientists at NGU are unsure how much fresh water remains.

Similar conditions found in the United States

Scientists from Columbia University in New York and the Woods Hole Oceanographic Institution in Massachusetts recently found fresh water in the Atlantic Ocean as well, along the east coast of the United States.

'It's the exact same phenomenon that we have here in Norway,' comments NGU project manager and marine geologist Jochen Knies.

The Atlantic Ocean aquifer extends along the coast from the southern tip of New Jersey to the northern end of Massachusetts. According to CNN, researchers estimated that it contains enough water to fill 1.1 billion swimming pools. This makes it the largest underwater freshwater aquifer found on Earth.

A possible resource

The findings in Norway and the US suggest that there may be other such aquifers elsewhere in the world.

'Such large pockets of fresh water could be a potential resource in areas with no drinking water on land,' Knies points out.

Credit: 
UiT The Arctic University of Norway

Math shows why animals see at night

IMAGE: Upper: simulation result by mathematical model, Below: live imaging data of experiment

Image: 
Sungrim Seirin-Lee/ Hiroshima University

Nocturnal and diurnal mammals see the same - but only for a brief time. When mice are born, the chromatin in the cells of their eyes has a diurnal structure. Day by day, the layout of this chromatin slowly inverts, allowing the mice to see at night. How this change happens was a mystery.

Sungrim Seirin-Lee, Associate Professor, and Hiroshi Ochiai, Lecturer, in the Graduate School of Integrated Sciences for Life at HU, suspected that the chromatin was making the shape of the nuclei change shape. "When we started this research, our hypothesis was based 100 percent on mathematics," Seirin-Lee said. "Because of our mathematical modeling, we found that nuclear deformation might be a key point in DNA's structure change."

If we could see inside of the nucleus, we would see that chromatin comes in different types and territories. Around the center of the nucleus is euchromatin, or DNA that is largely active. Heterochromatin, on another hand, is a kind of DNA that lies around the envelope or ceiling of the nucleus. Unlike euchromatin, the gene activation of heterochromatin is low.

Between nocturnal and diurnal animals, though, the differences in nuclear architecture get bigger - especially around the retina. The DNA is in the center of the nucleus in nocturnal mammals. Usually, heterochromatin stays put in the nuclear envelope. In the case of nocturnal animals, though, Seirin-Lee and Ochiai found it can be moved by the nucleus changing shape.

To describe the movement of chromatin, Seirin-Lee and her colleagues used a type of mathematical modeling called phase-field modeling. A method commonly used in physics; phase-field modeling can be used to do things like telling apart ice from water. However, according to Seirin-Lee, "it is not common in the biological sciences. In chromatin dynamics, it is the first trial in the world!" Using this function, the group could see the movement of chromatin and nucleus by determining and defining the inside and outside of the nucleus, as well as euchromatin versus heterochromatin.

When the group observed heterochromatin in the mouse's eyes, they found that conditional architecture triggered dynamic deformation, which resulted in an inverted nuclear architecture. In the inverted architecture case, two proteins are removed, which allows heterochromatin to move.

Then, with the assistance Ochiai, they put their model to the test on neural stem cells, which mimic retinal cells. After treating the cells with proteins that keep heterochromatin at the nuclear periphery, deformation stopped. Chromatin clustering increased, and nuclear architecture could not finish inverting. This finding was consistent with Lee's mathematical modeling.

Ultimately, Seirin-Lee and her colleagues want to see if their findings are universal to mammal cells. "At this stage, we think it is just mouse eyes," Seirin-Lee said, "but we don't know! Maybe humans could have such structures by dynamic nuclear deformation." Next, Seirin-Lee is looking to tackle the intermediate structure, or a sort of hybrid between conventional and inverted architecture of the nucleus.

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Hiroshima University

Review: Biofeedback could help treat a number of conditions

A literature review by a team at the VA Portland Health Care System and Oregon Health & Science University found evidence that biofeedback can be a helpful treatment for several conditions.
Studies show that biofeedback can reduce headache pain, improve both urinary and fecal incontinence, and aid in stroke recovery.

Dr. Karli Kondo of the VA Evidence Synthesis Program and OHSU, first author on the study, explained how the research could advance the use of biofeedback: "We are encouraged by the positive findings and the additional findings of potential benefits for a wide range of conditions. Biofeedback is a low-risk, cost-effective intervention. We hope that this report will help to make biofeedback more widely available to veterans across the U.S., and that it will serve as a roadmap for future research in the field."

The results appeared online Aug. 14, 2019, in the Journal of General Internal Medicine.

Biofeedback refers to using instruments to measure and provide real-time feedback on patients' physiological responses. It can help patients learn to control and change those responses. Since biofeedback does not involve medication and is relatively noninvasive compared to other treatments, it could benefit patients with a low risk of any adverse effects, say the researchers.

Biofeedback measures include muscle activity, heart rate, blood pressure, and brainwaves. It is often paired with treatments to change behavior, thoughts, or emotions. For example, using electromyography (EMG) to measure how muscles tighten in response to a medical condition may help patients consciously control those muscles.

Biofeedback increasingly is being used as a complementary or alternative treatment for a wide range of conditions. In 2017, about 70 VA facilities reported offering some form of biofeedback.

However, the evidence on how biofeedback is used and its effectiveness is scattered across studies on the individual conditions. Because of this, the practice is not well-integrated with usual care.

Kondo and colleagues created an "evidence map" to get a high-level overview of the research available on biofeedback. They searched for previously conducted systematic reviews and studies on biofeedback to summarize what has been found so far. In total, the researchers used 16 systematic reviews on the topic.

The review showed clear evidence that biofeedback is effective at reducing headache pain. A variety of biofeedback measures have been used for headache, including EMG, skin temperature, and blood pressure monitoring. These techniques appear to help decrease the frequency, duration, and intensity of both migraine and tension headaches. The largest improvements were in decreasing frequency of headaches. Moderate-confidence evidence shows that biofeedback can also improve secondary outcomes of headache, such as medication use, muscle tension, anxiety, and depression.

Strong evidence also exists showing that biofeedback can help with urinary incontinence for men who have had their prostate removed. In this case, EMG is used to assist with pelvic floor muscle training. Adding biofeedback provides both immediate and long-term improvements beyond those seen with muscle training alone.

The evidence map shows consistent evidence that biofeedback helps with several other conditions, although with fewer trials than were found for headaches or incontinence. EMG biofeedback can help with fecal incontinence in both older people of both sexes and in young women who recently gave birth. Adding biofeedback to therapy for lower-limb activity after stroke also appears to help patients. Stroke therapy can include several different types of biofeedback, such as platforms that measure weight distribution to help with balance, sensors to measure the angle of the joints during walking, and EMG to record muscle activity.

The researchers found studies on biofeedback use for several other conditions, but no compelling evidence that it was effective in those cases. Reviews showed no benefits from biofeedback for urinary incontinence in women or for high blood pressure management. However, the studies covering these conditions were limited. Likewise, the review turned up insufficient evidence for the use of biofeedback for other conditions, such as bruxism (grinding or clenching the teeth, often while sleeping), labor pain, and Reynaud's disease (a condition involving reduced blood flow to the extremities).

The researchers point out that their evidence map, in addition to showing several conditions for which biofeedback has been proven useful, also shows areas of uncertainty where more research is needed. They identified several targets for further research: balance and gait training, fibromyalgia, and intradialytic hypotension (a decrease in blood pressure that can cause a number of symptoms, including nausea, dizziness, and anxiety).

Overall, the evidence map gives a "lay of the land" that shows what evidence exists for using biofeedback to treat medical conditions or symptoms and what research is still needed.

Credit: 
Veterans Affairs Research Communications

Arctic permafrost melting will aggravate the greenhouse effect

Scientists from Russia and the United States studied the composition of the deep layers of permafrost in Eastern Siberia to better understand the hazards of permafrost thawing to our planet and its inhabitants. Their findings suggest that the release of organic matter from permafrost will intensify the greenhouse effect. The results of their study were published in the Journal of Geophysical Research.

Ice-coated ground that never thaws, permafrost accounts for nearly 25% of land on Earth. Permafrost has increasingly called the attention of the scientists due to global warming, since permafrost thawing may trigger extensive release of ancient organic carbon and possibly result in a huge environmental disaster. There is no clear understanding of the consequences of the permafrost meltdown which may be fraught with other risks aside from the global ocean level rise.

Scientists from the Skolkovo Institute of Science and Technology and Lomonosov Moscow State University in collaboration with researchers from Florida State University undertook the first ever study of organic matter contained in the deep permafrost layers in the Kolyma River basin in Eastern Siberia, aiming to understand what happened during permafrost thawing periods in the past and predict how present-day global warming may affect permafrost and what this could lead to. In the attempt to find out what organic material is buried under the layers of ice and what happens if it breaks loose, the scientists picked soil samples at depths of 3 to 15 meters from two deposits of different geological ages to study the soil molecular structure using mass spectrometry. The experiment showed that permafrost thawing may produce microbially degradable rich organic matter, which, in turn, will cause massive greenhouse emissions and make global warming even faster.

One of the authors of the study and Junior Research Scientist at Skoltech, Alexander Zherebker, PhD (Chemistry), stresses the significance of the study: "We examined Pleistocene and Holocene deposits representing a pool of carbon which is best conserved and was only partly transformed during the melting periods and contains 2% of organic matter and 90% of ice. We pinpointed the components that underwent the biggest change and those that are the most susceptible to microorganism action. It transpired that biodegradable components are present both at great depths and very close to the permafrost surface. According to our projections, the Arctic region will very soon have a marked impact on global warming."

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

Gene mutations coordinate to drive malignancy in lung cancer

Scientists have shown exactly how mutations in two different genes coordinate to drive the development of malignant lung tumors, according to a new report in the open-access journal eLife.

The study in novel genetically engineered mice looked at the characteristics of lung tumors from when they are invisibly small to when they are larger and potentially deadly. The results shed new light on the mechanisms of tumor progression and will help researchers currently developing drugs for lung tumors.

There are many types of lung cancer: non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death globally, and lung adenocarcinoma is the most common subtype of NSCLC. Around 75% of lung adenocarcinomas have mutations that affect two important control mechanisms for cell growth - the MAP kinase pathway, and the PI3'-kinase pathway. Each pathway alone is not sufficient to cause lung cancer; they need to coordinate to make this happen.

"We knew that mutations in the MAP kinase pathway promote the growth of benign lung tumors, but that PI3'-kinase mutations alone do not kickstart tumor formation in the same cells," explains lead author Ed van Veen, former Postdoctoral Fellow in senior author Martin McMahon's laboratory at Huntsman Cancer Institute (HCI) at the University of Utah (U of U), Salt Lake City, US. "The pathways instead cooperate to drive the growth of malignant tumors, but we didn't know what molecular changes occurred as a result of this cooperation and how the lung cells lose their characteristics as cancer develops."

The team studied mice with mutations that were only active in lung cells called Type 2 pneumocytes. They analyzed the effects of these mutations on the genes and protein molecules in individual cells at different stages of tumor development. When they looked at the gene expression of the MAP and PI3'-kinase-driven tumors, they found that the tumor cells had reduced levels of genes that are hallmarks of a Type 2 pneumocyte, suggesting that these lung cells had lost their identity.

Next, the team looked at which molecules were responsible for coordinating the MAP and PI3'- kinase pathways together. Fluorescent labeling of molecules already known to be involved in lung cell specialization showed some surprising results - these molecules did not play a role in the loss of lung cell identity that contributes to tumor progression. Rather, a molecule called PGC1α appeared to be involved.

To investigate if PGC1α directly controls the loss of Type 2 pneumocyte identity during lung tumor development, the team studied mice with a silenced version of the molecule, alongside mutations in the MAP kinase pathway. They found that silencing PGC1α causes lung cells to lose their specialized characteristics by cooperating with two other molecules that are required for this specialization.

"Taken together, our results shed light on the mechanisms by which pathways involved in lung tumor development also cooperate to influence the specialization of tumor cells," explains senior author Martin McMahon, Senior Director of Preclinical Translation at HCI and Professor of Dermatology at the U of U, Salt Lake City. "Since both MAP kinase and the PI3'-kinase pathways are targets for drug development, this study may influence the deployment of drugs currently in clinical trials, the interpretation of trial results and the process of novel lung cancer drug discovery."

Credit: 
eLife

Cancer cells' immune weak spot revealed

Scientists have found a vulnerability in cancer cells that could make them more susceptible to being destroyed by the immune system, according to a new report in eLife.

The discovery could make it possible to circumvent the resistance starting to be seen with a new generation of immunotherapy treatments called checkpoint inhibitors.

Scientists have been heralding immunotherapy treatments as breakthroughs in cancer research as they have prolonged life in some people with previously untreatable cancers. However, not everyone responds to immunotherapy and recent studies suggest that some cancers are able to escape the effects of checkpoint inhibitor drugs. As a result, there is considerable interest in finding ways to amplify the body's immune response to cancer.

"Anti-tumour immunity is not solely mediated by the adaptive immune system, but also by innate immune cells, most notably natural killer, or NK, cells," explains lead author Matthew Pech, a scientist in cancer immunology at Calico Life Sciences, South San Francisco, US. "In this study, we used genetic screening in a modified leukaemia cell line to find molecules in cancer cells that determine their response to NK cells."

The team used a gene-editing technique called CRISPR to tweak all the genes in the leukaemia cells, and then studied how this affected their interaction with NK cells. They were particularly interested in an important molecule called interferon-gamma (IFNγ), which immunotherapy-resistant tumour cells are often insensitive to. They found two broad classes of 'hits': genes involved in the tumour-NK cell interaction and components of the IFNγ signalling pathway. Among them was a novel molecule called DCAF15 - part of a family of 'adaptors' that provide specificity to the ubiquitination machinery. Ubiquitination controls many processes within cells, including protein turnover, proliferation and DNA repair.

To explore this molecule further, the team deleted DCAF15 from leukaemia cells and looked at how they responded to NK cells. They found that the absence of DCAF15 sensitised the leukaemia cells to the NK cells.

Having identified DCAF15 as a potential molecule that could sensitise cancer cells to the innate immune system, the team looked at whether an experimental anti-leukaemia drug called indisulam, which modulates the activity of DCAF15, would also affect the immune response.

As they hoped, they found in a range of blood cancer cells that indisulam caused a similar increase in a molecule called CD80, which provides important signals that amplify the immune response, as had been seen in the cells without DCAF15. This raised the possibility that drugs of this type could be used to boost the immune response towards cancer cells. Moreover, an analysis of data from patients with leukaemia found that reduced DCAF15 levels were linked to better survival of acute myeloid leukaemia (AML).

"We have identified DCAF15 as an important molecule in controlling the body's immune response to tumours," concludes senior author Jeff Settleman, who was Head of Oncology Research at Calico Life Sciences, South San Francisco, at the time the study was carried out. "The finding that an existing drug, indisulam, was able to reproduce the immune-promoting effects of deleting DCAF15, alongside our observation that AML patients with lower levels of DCAF15 had better clinical outcomes, suggest that blocking this molecule may be a beneficial strategy in the treatment of blood cancers."

Credit: 
eLife

Researchers discover a new form of immunotherapy

A new form of immunotherapy that has so far been tested on mice makes it probable, that oncologists in the future may be able to treat some of the patients who are not responding to existing types of immunotherapy. Instead of attacking the cancer cells directly, the new technique target and remove a subtype of immune cells known as macrophages, after which the immune system itself begins to attack the cancer.

This is shown by a new study published in the Journal of Experimental Medicine in which researchers from Aarhus University, Denmark, have collaborated with colleagues in France, the UK and USA, to show that the serious form of skin cancer 'malignant melanoma' can be defeated by using the new method. This variant of skin cancer accounts for eighty per cent of all deaths from melanomas.

"We've studied what happens to the tumour when it is exposed to targeted treatment that removes precisely ten per cent of the macrophages that are supporting the cancer tumour instead of fighting it," says Anders Etzerodt, PhD and assistant professor in cancer immunology at the Department of Biomedicine at Aarhus University.

He is the lead author of the study which is currently being shared diligently on Twitter by researchers in the field.

"The most important result is that the depletion of this specific type of macrophage causes the tumour to shrink, which is triggered by a subsequent mobilisation of new macrophages and, ultimately, also an activation of the so-called T cells which attack the tumour," says Anders Etzerodt.

The type of macrophages which the researchers have removed express a specific receptor, CD163, on the cell surface. Unlike other macrophages, these are known to have an undesirable effect in connection with cancer. Instead of recognising cancer cells as unwanted tissue, the macrophage sees the tumours as normal tissue that needs help with regeneration. It is also widely recognised that survival rates are worse if there are many macrophages, which express the CD163 receptor in the tumour.

"Our study suggests that the macrophages we're hitting function as a kind of 'peacekeeping' force that keeps the 'attackers' away," says Anders Etzerodt.

"When the peacekeeping macrophages in the tumour are removed, the attackers can instead be mobilised, after which the T cells and a number of other macrophages collaborate to attack the tumour. What's interesting is that the whole thing happens by itself as soon as we remove a tenth of the macrophages that express CD163, and that these appear to want to 'decide' which immune cells can be allowed to get into and out of the tumour," he says.

Anders Etzerodt adds that discovering that it is actually possible to target medical chemotherapy treatment so that it precisely hits the macrophages that are negative markers for survival is in itself an important finding.

Even though this is an example of a basic research breakthrough, it can easily take ten years before the new type of immunotherapy is offered as a treatment option in hospitals in Denmark.

The research group with Anders Etzerodt and research partners are currently testing whether the technique works just as well on mice with other kinds of cancer in which CD163 is a sign of low survival rates. These ongoing research projects focus on both cancer of the ovaries and cancer of the pancreas, and Anders Etzerodt does not hide the fact that there are still unanswered questions and issues that need to be dealt with:

"We don't know the long-term effects of removing macrophages, and we must also find partners to collaborate with and funding from foundations so we can conduct clinical trials on humans. But I believe we are well-prepared with strong proof-of-concept data and patent applications," says Anders Etzerodt, who has also worked on the idea in a leading French macrophage laboratory at the Centre d'Immunologie Marseille-Luminy. His stay here was made possible by a four-year postdoc fellowship from the Novo Nordisk Foundation.

Credit: 
Aarhus University

Mediating the trade-off -- How plants decide between growth or defense

image: HBI1 controls growth and defense responses through transcriptional regulation of ROS homeostasis. There is incompatibility between growth and defense programs.

Image: 
<i>Cell Reports</i>, CC BY-NC http://creativecommons.org/licenses/by-nc-nd/4.0/

Grow or defend yourself - a decision plants need to make on a daily basis, due to their inability to do both simultaneously. For a long time, it was thought that the reason for the growth-defence trade-off might be a question of energy resources. When a plant is defending itself against pathogens, energy could simply be limited for the plant to be growing at the same time, and vice versa. A recent paper published in Cell Reports shines a new light on the poorly understood mechanisms of the trade-off, clarifying that the actual underlying reasons is the incompatibility of the molecular pathways regulating plant growth and defence.

In addition to the observed trade-off, growth and defence need seemingly contradicting requirements. Growth is a process which often necessitates the loosening of the cell wall so that the cells have space to expand. Defence, in many cases calls for a tightening of the cell wall. In this way, the cells form a more solid barricade which is harder to penetrate for pathogens. Within their paper the researchers show that the growth-related transcriptional regulator HBl1 (Homolog of Bee2 Interacting with lBH 1) controls both processes within plants.

By differentially leveraging the expression of NADPH oxidases (NOXs) and peroxidases (POXs), HBl1 regulates ROS homeostasis within the apoplast (the space in between the cell walls of the plant). When plants need to grow, HBI1 is active and configures apoplastic ROS levels that support growth by activating specific NOX genes and repressing specific POX genes. In case of pathogen attack, HBI1 needs to be deactivated, resulting in increased apoplastic ROS levels through the activation of a NOX gene and several POX genes that represses growth but increase disease resistance within the plant.

Due to the contrasting nature of the two processes - both being regulated by the same transcription factor whilst requiring conflicting ROS levels - the researchers showed that the growth-defence trade-off is caused by the incompatibility of the pathways, and not by limited energy resources.

The project, which had started four years ago as a Bachelor thesis, was carried out in Aachen. Due to a recent move of the group supervisor, Dr. Schippers, to the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) in Gatersleben, the project was partially evaluated and written up at the Gaterslebener Institute. Dr. Schippers let us know: "With our current findings, we are starting to understand one of the mechanisms behind the growth-defence trade-off. This understanding is crucial if we want to improve plant biomass production without risking impairment of their ability to defend against pathogens."

Dr. Schippers' "Seed Development" research group at the IPK will continue to investigate the different pathways within plant seeds. Dr. Schippers: "As it stands, there are more than 70 peroxidases and 10 NADPH oxidases within plants and we don't exactly know what they are doing. They are of particular interest to me, as peroxidases and oxidases have similar effects within plants and animals. This indicates that their functional conservation predates that of hormones, as hormone signalling pathways evolved specific pathways in plants and humans. We aim to fully untangle these pathways at the cellular level - so that one day, we can reveal their regulation and function during the development of plants."

Credit: 
Leibniz Institute of Plant Genetics and Crop Plant Research

Intimate partner violence against women creates economic hardship, Rutgers study finds

Women who experience intimate partner violence, including physical, emotional, and controlling abuse, are more likely to suffer material hardship - the inability to purchase food, housing, utilities, medical care or other needs for a healthy life, according to a Rutgers-led study.

The study, in the journal Violence Against Women, found that experiencing intimate partner violence increases the probability that a woman will experience material hardship by 10-25 percent when factors such as ethnicity, education, mental health and drug use are accounted for. Analyses were based on nine years of longitudinal data from the Fragile Families and Child Wellbeing Study, which followed 5,000 women after the birth of a child in 20 large cities in the United States. Data were collected by researchers at Princeton and Columbia Universities.

Physical abuse, including being slapped, kicked, hit or experiencing sexual abuse, had the strongest association with material hardship, such that women who experienced this form of abuse reported 25% greater likelihood of being unable to purchase basic necessary items and services. Controlling abuse, which happens when a partner controls the victim by not allowing her to work or taking her wages, had the second-strongest association, increasing the likelihood of reporting material hardship by approximately 13%.

The study reinforced the idea that there are more than just physical ramifications in an abusive relationship.

Lenna Nepomnyaschy, co-author and associate professor at Rutgers University-New Brunswick's School of Social Work, said, "Many people don't realize the extent of the negative effects domestic violence has on victims. Policy makers need to be aware of these harmful effects on the economic stability and security of vulnerable families when there are discussions about provision of safety net benefits, such as food stamps, Medicaid, and other forms of public assistance."

She continued, "Our results are highly relevant in light of a new rule issued by the Trump administration and scheduled to go into effect October 15th, which would deny green cards for legal immigrants who receive any public assistance, including food stamps, Medicaid, and housing assistance, even when they are eligible for such programs. The most vulnerable women, those who are victims of domestic violence, poor, and immigrants, and their children would thus be the most negatively affected."

"Our study merges interpersonal violence and poverty research to make the case for an issue that people think of as a personal problem. Communities and families can be affected, with the possibility of electricity and water being shut off, eviction and food insecurity, which are all tremendously harmful for mothers and their children," said co-author Julia O'Connor, assistant professor at University of Central Florida and a graduate of the doctoral program at Rutgers University-New Brunswick's School of Social Work.

The study was based on a sample of 4,234 women, who were interviewed at the birth of their child and at four follow-up interviews over nine years, and who were involved in a relationship with either the biological father of the focal child or a new partner. Over the course of the study, approximately 40% of these women reported any material hardship and approximately 25% experienced some form of intimate partner violence.

Credit: 
Rutgers University

Land-use program fosters white-tailed deer populations in USA

A land-use program piloted in the United States is having a long-term positive impact on populations of white-tailed deer, according to new research by University of Alberta biologists.

The study examined the benefits of the Conservation Reserve Program (CRP) in North Dakota. Initiated in 1985, the CRP provides payment to farmers who convert sensitive land from agriculture production to vegetative cover, with the goal of improving water quality, preventing soil erosion, and building wildlife habitat.

"White-tailed deer tend to occur more, and in higher numbers, in areas with higher percentage of CRP," explained lead author Mariana Nagy-Reis, a postdoctoral fellow studying with Professor Mark Boyce in the Department of Biological Sciences. "Increased tall vegetative cover adds more complexity to the landscape--a characteristic that increases fawn survival."

The results also indicate that the CRP has positive effects on other bird and mammal populations by providing permanent cover and high-quality forage. In fact, Nagy-Reis explained, the benefits of CRP go beyond improving wildlife habitats.

"It improves the characteristics of the landscape--water, soil, and air--and it promotes increased ecological services such as pollination and pest control. Recent studies have shown that CRP has countless social, economic, and ecological values. It is a valuable tool for biodiversity conservation in general."

"Agriculture and wildlife can be compatible with creative solutions such as the CRP program," added Boyce. "Interspersing patches of uncultivated land on an agricultural landscape affords huge benefits for wildlife and also enhances carbon sequestration and storage in the soil."

Credit: 
University of Alberta