Indefinite Info.| good latest read: February 2020

Saturday, February 22, 2020

Scottish research could 'reverse effects of multiple sclerosis'

Pheno Therapeutics has secured more than 5 million of funding to search for new drugs to repair damage to the nervous system the disease causes and improve symptoms including problems with balance, speech, vision and

movement.

New treatments to reverse the effects of multiple sclerosis (MS) will be investigated by a new drug discovery company based on research from a Scottish university.

Pheno Therapeutics has secured more than £5 million of funding to search for new drugs to repair damage to the nervous system the disease causes and improve symptoms including problems with balance, speech, vision and movement.

It aims to develop new therapies for MS by identifying novel molecules that spark the body to repair a protective cover for nerve cells damaged the disease.

MS causes the immune system to attack the myelin sheath surrounding nerve cells, disrupting the signals travelling to the nerves.

Developing a remyelination process, as Pheno Theraputics hopes to, has the potential to slow or arrest the progressive disability MS patients face.

The company has secured funding over three years, subject to hitting certain milestones, from investment organisations and a medical research charity.

Pheno Therapeutics co-founder Professor Siddharthan Chandran said: "There are no interventions for people with later stage multiple sclerosis, which is a devastating and debilitating condition.

"The opportunity for this company is to bring new and repurposed therapeutics to clinical trials and, by doing so, meet an urgent and currently unmet need."

The university's commercialisation service, Edinburgh Innovations, helped to launch the company.

George Baxter, Edinburgh Innovations chief executive, said: "Everyone involved is focused on driving the science forward, and we look forward to supporting the team as momentum continues to build, ultimately offering the promise of new treatments."

Earliest interbreeding event between ancient human populations discovered

Neanderthal and modern human skulls (stock image).

For three years, anthropologist Alan Rogers has attempted to solve an evolutionary puzzle. His research untangles millions of years of human evolution by analyzing DNA strands from ancient human species known as hominins. Like many evolutionary geneticists, Rogers compares hominin genomes looking for genetic patterns such as mutations and shared genes. He develops statistical methods that infer the history of ancient human populations.

In 2017, Rogers led a study which found that two lineages of ancient humans, Neanderthals and Denisovans, separated much earlier than previously thought and proposed a bottleneck population size. It caused some controversy -- anthropologists Mafessoni and Prüfer argued that their method for analyzing the DNA produced different results. Rogers agreed, but realized that neither method explained the genetic data very well.

"Both of our methods under discussion were missing something, but what?" asked Rogers, professor of anthropology at the University of Utah.

The new study has solved that puzzle and in doing so, it has documented the earliest known interbreeding event between ancient human populations -- a group known as the "super-archaics" in Eurasia interbred with a Neanderthal-Denisovan ancestor about 700,000 years ago. The event was between two populations that were more distantly related than any other recorded. The authors also proposed a revised timeline for human migration out of Africa and into Eurasia. The method for analyzing ancient DNA provides a new way to look farther back into the human lineage than ever before.

"We've never known about this episode of interbreeding and we've never been able to estimate the size of the super-archaic population," said Rogers, lead author of the study. "We're just shedding light on an interval on human evolutionary history that was previously completely dark."

The paper was published on Feb. 20, 2020, in the journal Science Advances.

Out of Africa and interbreeding

Rogers studied the ways in which mutations are shared among modern Africans and Europeans, and ancient Neanderthals and Denisovans. The pattern of sharing implied five episodes of interbreeding, including one that was previously unknown. The newly discovered episode involves interbreeding over 700,000 years ago between a distantly related "super-archaic" population which separated from all other humans around two million years ago, and the ancestors of Neanderthals and Denisovans.

The super-archaic and Neanderthal-Denisovan ancestor populations were more distantly related than any other pair of human populations previously known to interbreed. For example, modern humans and Neanderthals had been separated for about 750,000 years when they interbred. The super-archaics and Neanderthal-Denisovan ancestors were separated for well over a million years.

"These findings about the timing at which interbreeding happened in the human lineage is telling something about how long it takes for reproductive isolation to evolve," said Rogers.

The authors used other clues in the genomes to estimate when the ancient human populations separated and their effective population size. They estimated the super-archaic separated into its own species about two million years ago. This agrees with human fossil evidence in Eurasia that is 1.85 million years old.

The researchers also proposed there were three waves of human migration into Eurasia. The first was two million years ago when the super-archaics migrated into Eurasia and expanded into a large population. Then 700,000 years ago, Neanderthal-Denisovan ancestors migrated into Eurasia and quickly interbred with the descendants of the super-archaics. Finally, modern humans expanded to Eurasia 50,000 years ago where we know they interbred with other ancient humans, including with the Neanderthals.

"I've been working for the last couple of years on this different way of analyzing genetic data to find out about history," said Rogers. "It's just gratifying that you come up with a different way of looking at the data and you end up discovering things that people haven't been able to see with other methods."

Nathan S. Harris and Alan A. Achenbach from the Department of Anthropology at the University of Utah also contributed to the study.

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Wednesday, February 19, 2020

9 - Official Trailer the scariest movie

Saturday, February 8, 2020

Eating red meat and processed meat hikes heart disease and death risk, study finds

Processed meats (stock image).

After a controversial study last fall recommending that it was not necessary for people to change their diet in terms of red meat and processed meat, a large, carefully analyzed new study links red and processed meat consumption with slightly higher risk of heart disease and death, according to a new study from Northwestern Medicine and Cornell University.

Eating two servings of red meat, processed meat or poultry -- but not fish -- per week was linked to a 3 to 7% higher risk of cardiovascular disease, the study found. Eating two servings of red meat or processed meat -- but not poultry or fish -- per week was associated with a 3% higher risk of all causes of death.

"It's a small difference, but it's worth trying to reduce red meat and processed meat like pepperoni, bologna and deli meats," said senior study author Norrina Allen, associate professor of preventive medicine at Northwestern University Feinberg School of Medicine. "Red meat consumption also is consistently linked to other health problems like cancer."

"Modifying intake of these animal protein foods may be an important strategy to help reduce the risk of cardiovascular disease and premature death at a population level," said lead study author Victor Zhong, assistant professor of nutritional sciences at Cornell, who did the research when he was a postdoctoral fellow in Allen's lab.

The paper will be published Feb. 3 in JAMA Internal Medicine.

The new findings come on the heels of a controversial meta-analysis published last November that recommended people not reduce the amount of red meat and processed meat they eat. "Everyone interpreted that it was OK to eat red meat, but I don't think that is what the science supports," Allen said.

"Our study shows the link to cardiovascular disease and mortality was robust," Zhong said.

What should we eat?

"Fish, seafood and plant-based sources of protein such as nuts and legumes, including beans and peas, are excellent alternatives to meat and are under-consumed in the U.S.," said study coauthor Linda Van Horn, professor of preventive medicine at Feinberg who also is a member of the 2020 U.S. Dietary Guidelines Advisory committee.

The study found a positive association between poultry intake and cardiovascular disease, but the evidence so far isn't sufficient to make a clear recommendation about poultry intake, Zhong said. Still, fried chicken is not recommended.

The new study pooled together a large diverse sample from six cohorts, included long follow-up data up to three decades, harmonized diet data to reduce heterogeneity, adjusted a comprehensive set of confounders and conducted multiple sensitivity analyses. The study included 29,682 participants (mean age of 53.7 years at baseline, 44.4% men and 30.7% non-white). Diet data were self-reported by participants, who were asked a long list of what they ate for the previous year or month.

Key findings:

A 3 to 7% higher risk of cardiovascular disease and premature death for people who ate red meat and processed meat two servings a week.
A 4% higher risk of cardiovascular disease for people who ate two servings per week of poultry, but the evidence so far is not sufficient to make a clear recommendation about poultry intake. And the relationship may be related to the method of cooking the chicken and consumption of the skin rather than the chicken meat itself.
No association between eating fish and cardiovascular disease or mortality.

Limitations of the study are participants' dietary intake was assessed once, and dietary behaviors may have changed over time. In addition, cooking methods were not considered. Fried chicken, especially deep fat-fried sources that contribute trans-fatty acids, and fried fish intake have been positively linked to chronic diseases, Zhong said.

Other Northwestern authors are Dr. Philip Greenland, Dr. Mercedes R. Carnethon, Dr. Hongyan Ning, Dr. John T. Wilkins and Dr. Donald M. Lloyd-Jones.

The study was funded by National Institutes of Health/National Heart, Lung, and Blood Institute (R21 HL085375), American Heart Association Strategically Focused Research Networks and the Feinberg School of Medicine.

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Materials provided by Northwestern University. Original written by Marla Paul. Note: Content may be edited for style and length.

First childhood flu helps explain why virus hits some people harder than others

Taking temperature of child (stock image).

Why are some people better able to fight off the flu than others? Part of the answer, according to a new study, is related to the first flu strain we encounter in childhood.

Scientists from UCLA and the University of Arizona have found that people's ability to fight off the flu virus is determined not only by the subtypes of flu they have had throughout their lives, but also by the sequence in which they are been infected by the viruses. Their study is published in the open-access journal PLoS Pathogens.

The research offers an explanation for why some people fare much worse than others when infected with the same strain of the flu virus, and the findings could help inform strategies for minimizing the effects of the seasonal flu.

In addition, UCLA scientists, including Professor James Lloyd-Smith, who also was a senior author of the PLoS Pathogens research, recently completed a study that analyzes travel-related screening for the new novel coronavirus 2019-nCoV.

The researchers report that screening travelers is not very effective for the 2019 coronavirus -- that it will catch less than half of infected travelers, on average -- and that most infected travelers are undetectable, meaning that they have no symptoms yet, and are unaware that they have been exposed. So stopping the spread of the virus is not a matter of just enhancing screening methods at airports and other travel hubs.

"This puts the onus on government officials and public health officials to follow up with travelers after they arrive, to isolate them and trace their contacts if they get sick later," said Lloyd-Smith, a UCLA professor of ecology and evolutionary biology. Many governments have started to impose quarantines, or even travel bans, as they realize that screening is not sufficient to stop the spread of the coronavirus.

One major concern, Lloyd-Smith said, is that other countries, especially developing nations, lack the infrastructure and resources for those measures, and are therefore vulnerable to importing the disease.

"Much of the public health world is very concerned about the virus being introduced into Africa or India, where large populations exist do not have access to advanced medical care," he said.

The researchers, including scientists from the University of Chicago and the London School of Tropical Hygiene and Medicine, have developed a free online app where people can calculate the effectiveness of travel screening based on a range of parameters.

Solving a decades-old question

The PLoS Pathogens study may help solve a problem that had for decades vexed scientists and health care professionals: why the same strain of the flu virus affects people with various degrees of severity.

A team that included some of the same UCLA and Arizona scientists reported in 2016 that exposure to influenza viruses during childhood gives people partial protection for the rest of their lives against distantly related influenza viruses. Biologists call the idea that past exposure to the flu virus determines a person's future response to infections "immunological imprinting."

The 2016 research helped overturn a commonly held belief that previous exposure to a flu virus conferred little or no immunological protection against strains that can jump from animals into humans, such as those causing the strains known as swine flu or bird flu. Those strains, which have caused hundreds of spillover cases of severe illness and death in humans, are of global concern because they could gain mutations that allow them to readily jump not only from animal populations to humans, but also to spread rapidly from person to person.

In the new study, the researchers investigated whether immunological imprinting could explain people's response to flu strains already circulating in the human population and to what extent it could account for observed discrepancies in how severely the seasonal flu affects people in different age groups.

To track how different strains of the flu virus affect people at different ages, the team analyzed health records that the Arizona Department of Health Services obtains from hospitals and private physicians.

Two subtypes of influenza virus, H3N2 and H1N1, have been responsible for seasonal outbreaks of the flu over the past several decades. H3N2 causes the majority of severe cases in high-risk elderly people and the majority of deaths from the flu. H1N1 is more likely to affect young and middle-aged adults, and causes fewer deaths.

The health record data revealed a pattern: People first exposed to the less severe strain, H1N1, during childhood were less likely to end up hospitalized if they encountered H1N1 again later in life than people who were first exposed to H3N2. And people first exposed to H3N2 received extra protection against H3N2 later in life.

The researchers also analyzed the evolutionary relationships between the flu strains. H1N1 and H3N2, they learned, belong to two separate branches on the influenza "family tree," said James Lloyd-Smith, a UCLA professor of ecology and evolutionary biology and one of the study's senior authors. While infection with one does result in the immune system being better prepared to fight a future infection from the other, protection against future infections is much stronger when one is exposed to strains from the same group one has battled before, he said.

The records also revealed another pattern: People whose first childhood exposure was to H2N2, a close cousin of H1N1, did not have a protective advantage when they later encountered H1N1. That phenomenon was much more difficult to explain, because the two subtypes are in the same group, and the researchers' earlier work showed that exposure to one can, in some cases, grant considerable protection against the other.

"Our immune system often struggles to recognize and defend against closely related strains of seasonal flu, even though these are essentially the genetic sisters and brothers of strains that circulated just a few years ago," said lead author Katelyn Gostic, who was a UCLA doctoral student in Lloyd-Smith's laboratory when the study was conducted and is now a postdoctoral fellow at the University of Chicago. "This is perplexing because our research on bird flu shows that deep in our immune memory, we have some ability to recognize and defend against the distantly related, genetic third cousins of the strains we saw as children.

"We hope that by studying differences in immunity against bird flus -- where our immune system shows a natural ability to deploy broadly effective protection -- and against seasonal flus -- where our immune system seems to have bigger blind spots -- we can uncover clues useful to universal influenza vaccine development."

Around the world, influenza remains a major killer. The past two flu seasons have been more severe than expected, said Michael Worobey, a co-author of the study and head of the University of Arizona's department of ecology and evolutionary biology. In the 2017-18 season, 80,000 people died in the U.S., more than in the swine flu pandemic of 2009, he said.

People who had their first bout of flu as children in 1955 -- when the H1N1 was circulating but the H3N2 virus was not -- were much more likely to be hospitalized with an H3N2 infection than an H1N1 infection last year, when both strains were circulating, Worobey said.

"The second subtype you're exposed to is not able to create an immune response that is as protective and durable as the first," he said.

The researchers hope that their findings could help predict which age groups might be severely affected during future flu seasons based on the subtype circulating. That information could also help health officials prepare their response, including decisions about who should receive certain vaccines that are only available in limited quantities.

The research was funded by the National Institutes of Health, the National Science Foundation, DARPA and the David and Lucile Packard Foundation. In 2018, the NIH's National Institute of Allergy and Infectious Diseases announced a strategic plan to develop a universal flu vaccine.

The study's co-authors are Rebecca Bridge of the Arizona Department of Health Services and Cecile Viboud of the Fogarty International Center at the NIH.

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Materials provided by University of California - Los Angeles. Original written by Stuart Wolpert and Daniel Stolte. Note: Content may be edited for style and length.

Red alert as Arctic lands grow greener

Arctic tundra in summer (stock image).

New research techniques are being adopted by scientists tackling the most visible impact of climate change -- the so-called greening of Arctic regions.

The latest drone and satellite technology is helping an international team of researchers to better understand how the vast, treeless regions called the tundra is becoming greener.

As Arctic summer temperatures warm, plants are responding. Snow is melting earlier and plants are coming into leaf sooner in spring. Tundra vegetation is spreading into new areas and where plants were already growing, they are now growing taller.

Understanding how data captured from the air compare with observations made on the ground will help to build the clearest picture yet of how the northern regions of Europe, Asia and North America are changing as the temperature rises.

Now a team of 40 scientists from 36 institutions, led by two National Geographic Explorers, have revealed that the causes of this greening process are more complex -- and variable -- than was previously thought.

Researchers from Europe and North America are finding that the Arctic greening observed from space is caused by more than just the responses of tundra plants to warming on the ground. Satellites are also capturing other changes including differences in the timing of snowmelt and the wetness of landscapes.

Lead author Dr Isla Myers-Smith, of the University of Edinburgh's School of GeoSciences, said: "New technologies including sensors on drones, planes and satellites, are enabling scientists to track emerging patterns of greening found within satellite pixels that cover the size of football fields."

Professor Scott Goetz of the School of Informatics, Computing and Cyber Systems at Northern Arizona University, says this research is vital for our understanding of global climate change. Tundra plants act as a barrier between the warming atmosphere and huge stocks of carbon stored in frozen ground.

Changes in vegetation alter the balance between the amount of carbon captured and its release into the atmosphere. Small variations could significantly impact efforts to keep warming below 1.5 degrees centigrade -- a key target of the Paris Agreement. The study will help scientists to figure out which factors will speed up or slow down warming.

Co-lead author Dr Jeffrey Kerby, who was a Neukom Fellow at Dartmouth College while conducting the research, said: "Besides collecting new imagery, advances in how we process and analyse these data -- even imagery that is decades old -- are revolutionising how we understand the past, present, and future of the Arctic."

Alex Moen, Vice President of Explorer Programs at the National Geographic Society, said: "We look forward to the impact that this work will have on our collective understanding of the Arctic for generations to come."

The paper, published in Nature Climate Change, was funded in part by the National Geographic Society and government agencies in the UK, North America and Europe, including NASA's Arctic Boreal Vulnerability Experiment (ABoVE) and the UK's Natural Environment Research Council.

The research was also supported by the Synthesis Centre of the German Centre for Integrative Biodiversity Research, and was informed by a U.S. National Academy of Sciences workshop, Understanding Northern Latitude Vegetation Greening and Browning.

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Materials provided by University of Edinburgh. Note: Content may be edited for style and length.

Grey seals discovered clapping underwater to communicate

Seal swimming underwater (stock image).

Marine mammals like whales and seals usually communicate vocally using calls and whistles.

But now a Monash University-led international study has discovered that wild grey seals can also clap their flippers underwater during the breeding season, as a show of strength that warns off competitors and advertises to potential mates.

This is the first time a seal has been seen clapping completely underwater using its front flippers.

"The discovery of 'clapping seals' might not seem that surprising, after all, they're famous for clapping in zoos and aquaria," said lead study author Dr David Hocking from Monash University's School of Biological Sciences.

"But where zoo animals are often trained to clap for our entertainment -- these grey seals are doing it in the wild of their own accord."

The research, published today in the journal Marine Mammal Science, is based on video footage collected by naturalist Dr Ben Burville, a Visiting Researcher with Newcastle University, UK.

The footage -- which took Dr Burville 17 years of diving to catch on film -- shows a male grey seal clapping its paw-like flippers to produce a gunshot-like 'crack!' sound.

"The clap was incredibly loud and at first I found it hard to believe what I had seen," Dr Burville said.

"How could a seal make such a loud clap underwater with no air to compress between its flippers?"

"Other marine mammal species can produce similar types of percussive sound by slapping the water with their body or tail," said Associate Professor Alistair Evans from Monash University, who was also involved in the study.

The loud high-frequency noise produced by clapping cuts through background noise, sending out a clear signal to any other seals in the area.

"Depending on the context, the claps may help to ward off competitors and/or attract potential mates," Dr Hocking said.

"Think of a chest-beating male gorilla, for example. Like seal claps, those chest beats carry two messages: I am strong, stay away; and I am strong, my genes are good."

Dr Hocking said clapping seals demonstrates just how much there still is to learn about the animals living around us.

Clapping appears to be an important social behaviour for grey seals, so anything that disturbed it could impact breeding success and survival for this species.

"Human noise pollution is known to interfere with other forms of marine mammal communication, including whale song," Dr Hocking said.

"But if we do not know a behaviour exists, we cannot easily act to protect it."

Understanding the animals around us better may just help us to protect them, and their way of life.

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Materials provided by Monash University. Note: Content may be edited for style and length.

Genome stability: Intricate process of DNA repair discovered

DNA illustration (stock image).

An elaborate system of filaments, liquid droplet dynamics and protein connectors enables the repair of some damaged DNA in the nuclei of cells, researchers at the University of Toronto have found. The findings further challenge the belief that broken DNA floats aimlessly -- and highlight the value of cross-disciplinary research in biology and physics.

DNA repair helps ensure genome stability, which in turn allows cells to function and promotes health in all organisms. Double-strand DNA breaks are especially toxic to cells, and researchers had assumed for decades that these breaks floated inside cell nuclei without direction, until they trigger other cellular changes or happen on a fixer mechanism.

That thinking began to change in 2015, when Karim Mekhail and his lab showed that damaged DNA can be intentionally transported by motor protein 'ambulances' to DNA 'hospitals,' areas enriched with certain repair factors in the nuclei. The researchers later worked with U of T aerospace engineers to show that after a single double-strand break, DNA travels for repair via long 'autobahns' of thread-like microtubules, which are also moving.

In the current study, Mekhail and lead author Roxanne Oshidari looked at yeast cells with many DNA double-strand breaks, and showed that coordination between shorter types of microtubule filaments and liquid-like droplets composed of DNA repair proteins enables the creation and function of a DNA repair centre.

"The liquid droplets work with intranuclear microtubules to promote the clustering of damaged DNA sites," says Mekhail, an associate professor of laboratory medicine and pathobiology at U of T. "Repair proteins at these different sites assemble in droplets that fuse into a larger repair-centre droplet, through the action of the shorter nuclear microtubules."

This larger oil-like droplet then behaves like a spider, says Mekhail, shooting out a web of star-shaped filaments that tether to the longer autobahns along which damaged DNA can be transported to the DNA hospitals.

The journal Nature Communications published the findings today.

Mekhail turned to Nasser Ashgriz, a professor in U of T's department of mechanical and industrial engineering, to measure and understand the role of droplets in the repair process. "You couldn't ask for better expertise in fluid dynamics, and he was just across the road," Mekhail says of Ashgriz, who runs U of T's multi-phase flow and spray systems lab.

Mekhail brought a video of the droplets to Ashgriz, who projected it on a large screen in his office and confirmed that fluid dynamics appeared to be at play. But communication across the biology-physics divide was challenging. "Understanding what they do was very difficult in the beginning because our terminologies are totally different," says Ashgriz.

When he and Mekhail used plain language to describe how the droplets behaved, however, things started to make sense. "We focused on the physical aspects of the droplets," Ashgriz says. "The physics that cause their motion and dynamics became our common language."

After months of talks and experiments, computer simulations repeatedly predicted that the shorter filaments would move like pistons, lowering pressure in the nucleoplasm and creating a suction effect that leads to the fusion of droplets. Mekhail and his team confirmed that finding in their lab.

"Often when we dive deep in the specifics of a field, we get separated from one another," Ashgriz says. "Bringing together people with different views can really improve understanding, and this work was a good example -- with credit to Karim for his vision and initiative."

Mekhail and his team also uncovered further important properties of the repair droplets with U of T professors Hyun Kate Lee and Haley Wyatt in the department of biochemistry, in a process Mekhail likens to play with toys. They ran the droplets through many tests, bouncing them against each other and observing their behaviour, which turned out to be very similar in a petri dish and in cells.

The most surprising finding came after several cycles of droplet fusion, the researchers found. "It was very bizarre and totally unexpected, I still remember the day," Mekhail says. Oshidari observed that the larger droplets initiate an internal concentration of filament building blocks, forcing creation of a kind of self-interlocking brick road, which together with the spidery webs allow DNA to hook onto the longer autobahn filaments.

The complex process is easy to miss when looking at DNA damage sites, says Mekhail, largely because imaging in the field has become highly automated. Most software has been set up to see what has already been seen. "We can't rely on the old ways of observing," he says. "We need to update our software and also go back to looking with the human eye, guided by simulations when needed."

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Materials provided by University of Toronto. Original written by Jim Oldfield. Note: Content may be edited for style and length.

Normal resting heart rate appears to vary widely from person to person

Monitoring heart rate (stock image).

A person's normal resting heart rate is fairly consistent over time, but may vary from others' by up to 70 beats per minute, according to analysis of the largest dataset of daily resting heart rate ever collected. Giorgio Quer of the Scripps Research Translational Institute in La Jolla, California, and colleagues present these findings in the open-access journal PLOS ONE on February 5, 2020 as part of an upcoming PLOS Collection on Digital Health Technology.

A routine visit to the doctor usually involves a measurement of resting heart rate, but such measurements are rarely actionable unless they deviate significantly from a "normal" range established by population-level studies. However, wearables that track heart rate now provide the opportunity to continuously monitor heart rate over time, and identify normal resting heart rates at the individual level.

In the largest study of its kind to date, Quer and colleagues retrospectively analyzed de-identified heart rate data from wearables worn for a median of 320 days by 92,457 people from across the U.S. Nearly 33 million days' worth of heart rate data were collected in total. The researchers used the data to examine variations in resting heart rate for individuals over time, as well as between individuals with different characteristics.

The analysis showed that one person's mean daily resting heart rate may differ by up to 70 beats per minute from another person's normal rate. Taken together, age, sex, body mass index (BMI), and average daily sleep duration accounted for less than 10 percent of the observed variation between individuals.

The authors observed also a small seasonal trend in the resting heart rate, with slightly higher values observed in January and slightly lower values in July. The researchers also found that some individuals may occasionally experience brief periods when their resting heart rate differs by 10 or more beats per minute from their normal range.

These findings suggest the potential value of further research to investigate whether tracking a person's daily resting heart rate could enable earlier detection of clinically important changes.

The authors add: "Day-to-day changes in resting heart rate could be the first true, individualized digital vital sign, which is only now possible to measure thanks to wearable sensor technologies. We analyzed the extent of inter- and intra-individual changes in resting heart rate over a prolonged period of time, showing distinct patterns of variation according to age and sex, time of the year, average sleep duration and body mass index. These variations in resting heart rate may allow for the identification of early unexpected changes in an individuals' health."

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Materials provided by PLOS. Note: Content may be edited for style and length.

Molecular 'switch' reverses chronic inflammation and aging

Hourglass, aging concept (stock image).

Chronic inflammation, which results when old age, stress or environmental toxins keep the body's immune system in overdrive, can contribute to a variety of devastating diseases, from Alzheimer's and Parkinson's to diabetes and cancer.

Now, scientists at the University of California, Berkeley, have identified a molecular "switch" that controls the immune machinery responsible for chronic inflammation in the body. The finding, which appears online Feb. 6 in the journal Cell Metabolism, could lead to new ways to halt or even reverse many of these age-related conditions.

"My lab is very interested in understanding the reversibility of aging," said senior author Danica Chen, associate professor of metabolic biology, nutritional sciences and toxicology at UC Berkeley. "In the past, we showed that aged stem cells can be rejuvenated. Now, we are asking: to what extent can aging be reversed? And we are doing that by looking at physiological conditions, like inflammation and insulin resistance, that have been associated with aging-related degeneration and diseases."

In the study, Chen and her team show that a bulky collection of immune proteins called the NLRP3 inflammasome -- responsible for sensing potential threats to the body and launching an inflammation response -- can be essentially switched off by removing a small bit of molecular matter in a process called deacetylation.

Overactivation of the NLRP3 inflammasome has been linked to a variety of chronic conditions, including multiple sclerosis, cancer, diabetes and dementia. Chen's results suggest that drugs targeted toward deacetylating, or switching off, this NLRP3 inflammasome might help prevent or treat these conditions and possibly age-related degeneration in general.

"This acetylation can serve as a switch," Chen said. "So, when it is acetylated, this inflammasome is on. When it is deacetylated, the inflammasome is off."

By studying mice and immune cells called macrophages, the team found that a protein called SIRT2 is responsible for deacetylating the NLRP3 inflammasome. Mice that were bred with a genetic mutation that prevented them from producing SIRT2 showed more signs of inflammation at the ripe old age of two than their normal counterparts. These mice also exhibited higher insulin resistance, a condition associated with type 2 diabetes and metabolic syndrome.

The team also studied older mice whose immune systems had been destroyed with radiation and then reconstituted with blood stem cells that produced either the deacetylated or the acetylated version of the NLRP3 inflammasome. Those who were given the deacetylated, or "off," version of the inflammasome had improved insulin resistance after six weeks, indicating that switching off this immune machinery might actually reverse the course of metabolic disease.

"I think this finding has very important implications in treating major human chronic diseases," Chen said. "It's also a timely question to ask, because in the past year, many promising Alzheimer's disease trials ended in failure. One possible explanation is that treatment starts too late, and it has gone to the point of no return. So, I think it's more urgent than ever to understand the reversibility of aging-related conditions and use that knowledge to aid a drug development for aging-related diseases."

Co-authors of the study include Ming He, Hou-Hsien Chiang and Hanzhi Luo, previously at UC Berkeley where the research was carried out; Zhifang Zheng, Mingdian Tan, Rika Ohkubo and Wei-Chieh Mu at UC Berkeley; Qi Qiao, Li Wang and Hao Wu at Harvard Medical School; and Shimin Zhao at Fudan University.

This research was supported in part by the National Institutes of Health under grants R01DK117481, R01DK101885, R01AG063404, R01AG 063389, DP1HD087988 and R01Al124491; the National Institute of Food and Agriculture; the France-Berkeley Fund, a Glenn/AFAR Scholarship; the Dr. and Mrs. James C.Y. Soong Fellowship; the Government Scholarship for Study Abroad (GSSA) from Taiwan; the ITO Foundation Scholarship and the Honjo International Scholarship.

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Materials provided by University of California - Berkeley. Original written by Kara Manke. Note: Content may be edited for style and length.