scientists

In Breakthrough, Scientists Edit a Dangerous Mutation From Genes in Human Embryos

Scientists for the first time have successfully edited genes in human embryos to repair a common and serious disease-causing mutation, producing apparently healthy embryos, according to a study published on Wednesday.

The research marks a major milestone and, while a long way from clinical use, it raises the prospect that gene editing may one day protect babies from a variety of hereditary conditions.

But the achievement is also an example of human genetic engineering, once feared and unthinkable, and is sure to renew ethical concerns that some might try to design babies with certain traits, like greater intelligence or athleticism.

Scientists have long feared the unforeseen medical consequences of making inherited changes to human DNA. The cultural implications may be just as disturbing: Some experts have warned that unregulated genetic engineering may lead to a new form of eugenics, in which people with means pay to have children with enhanced traits even as those with disabilities are devalued.

The study, published in the journal Nature, comes just months after a national scientific committee recommended new guidelines for modifying embryos, easing blanket proscriptions but urging the technique be used only for dire medical problems.

 

“We’ve always said in the past gene editing shouldn’t be done, mostly because it couldn’t be done safely,” said Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology who co-led the committee. “That’s still true, but now it looks like it’s going to be done safely soon,” he said, adding that the research is “a big breakthrough.”

“What our report said was, once the technical hurdles are cleared, then there will be societal issues that have to be considered and discussions that are going to have to happen. Now’s the time.”

Scientists at Oregon Health and Science University, with colleagues in California, China and South Korea, reported that they repaired dozens of embryos, fixing a mutation that causes a common heart condition that can lead to sudden death later in life.

If embryos with the repaired mutation were allowed to develop into babies, they would not only be disease-free but also would not transmit the disease to descendants.

The researchers averted two important safety problems: They produced embryos in which all cells — not just some — were mutation-free, and they avoided creating unwanted extra mutations.

“It feels a bit like a ‘one small step for (hu)mans, one giant leap for (hu)mankind’ moment,” Jennifer Doudna, a biochemist who helped discover the gene-editing method used, called CRISPR-Cas9, said in an email.

Gene Editing in Embryos
Scientists tried two techniques to remove a dangerous mutation. In the first, genetic “scissors” were inserted into fertilized eggs. The mutation was repaired in some of the resulting embryos but not always in every cell. The second method worked better: By injecting the “scissors” along with the sperm into the egg, more embryos emerged with repaired genes in every cell.

FIRST TECHNIQUE
When gene-editing components were introduced into a fertilized egg, some embryos contained a patchwork of repaired and unrepaired cells.

“I expect these results will be encouraging to those who hope to use human embryo editing for either research or eventual clinical purposes,” said Dr. Doudna, who was not involved in the study.

Much more research is needed before the method could be tested in clinical trials, currently impermissible under federal law. But if the technique is found to work safely with this and other mutations, it might help some couples who could not otherwise have healthy children.

Potentially, it could apply to any of more than 10,000 conditions caused by specific inherited mutations. Researchers and experts said those might include breast and ovarian cancer linked to BRCA mutations, as well as diseases like Huntington’s, Tay-Sachs, beta thalassemia, and even sickle cell anemia, cystic fibrosis or some cases of early-onset Alzheimer’s.

“You could certainly help families who have been blighted by a horrible genetic disease,” said Robin Lovell-Badge, a professor of genetics and embryology at the Francis Crick Institute in London, who was not involved in the study.

“You could quite imagine that in the future the demand would increase. Maybe it will still be small, but for those individuals it will be very important.”

The researchers also discovered something unexpected: a previously unknown way that embryos repair themselves.

In other cells in the body, the editing process is carried out by genes that copy a DNA template introduced by scientists. In these embryos, the sperm cell’s mutant gene ignored that template and instead copied the healthy DNA sequence from the egg cell.

“We were so surprised that we just couldn’t get this template that we made to be used,” said Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University and senior author of the study. “It was very new and unusual.”

The research significantly improves upon previous efforts. In three sets of experiments in China since 2015, researchers seldom managed to get the intended change into embryonic genes.

And some embryos had cells that did not get repaired — a phenomenon called mosaicism that could result in the mutation being passed on — as well as unplanned mutations that could cause other health problems.

In February, a National Academy of Sciences, Engineering and Medicine committee endorsed modifying embryos, but only to correct mutations that cause “a serious disease or condition” and when no “reasonable alternatives” exist.
Sheldon Krimsky, a bioethicist at Tufts University, said the main uncertainty about the new technique was whether “reasonable alternatives” to gene editing already exist.

As the authors themselves noted, many couples use pre-implantation genetic diagnosis to screen embryos at fertility clinics, allowing only healthy ones to be implanted. For these parents, gene editing could help by repairing mutant embryos so that more disease-free embryos would be available for implantation.

Hank Greely, director of the Center for Law and the Biosciences at Stanford, said creating fewer defective embryos also would reduce the number discarded by fertility clinics, which some people oppose.
The larger issue is so-called germline engineering, which refers to changes made to embryo that are inheritable.

“If you’re in one camp, it’s a horror to be avoided, and if you’re in the other camp, it’s desirable,” Dr. Greely said. “That’s going to continue to be the fight, whether it’s a feature or a bug.”

For now, the fight is theoretical. Congress has barred the Food and Drug Administration from considering clinical trials involving germline engineering. And the National Institutes of Health is prohibited from funding gene-editing research in human embryos. (The new study was funded by Oregon Health and Science University, the Institute for Basic Science in South Korea, and several foundations.)

The authors say they hope that once the method is optimized and studied with other mutations, officials in the United States or another country will allow regulated clinical trials.

“I think it could be widely used, if it’s proven safe,” said Dr. Paula Amato, a co-author of the study and reproductive endocrinologist at O.H.S.U. Besides creating more healthy embryos for in vitro fertilization, she said, it could be used when screening embryos is not an option or to reduce arduous IVF cycles for women.

Dr. Mitalipov has pushed the scientific envelope before, generating ethical controversy with a so-called three-parent baby procedure that would place the nucleus of the egg of a woman with defective cellular mitochondria into the egg from a healthy woman. The F.D.A. has not approved trials of the method, but Britain may begin one soon.

The new study involves hypertrophic cardiomyopathy, a disease affecting about one in 500 people, which can cause sudden heart failure, often in young athletes.

It is caused by a mutation in a gene called MYBPC3. If one parent has a mutated copy, there is a 50 percent chance of passing the disease to children.
Using sperm from a man with hypertrophic cardiomyopathy and eggs from 12 healthy women, the researchers created fertilized eggs. Injecting CRISPR-Cas9, which works as a genetic scissors, they snipped out the mutated DNA sequence on the male MYBPC3 gene.

They injected a synthetic healthy DNA sequence into the fertilized egg, expecting that the male genome would copy that sequence into the cut portion. That is how this gene-editing process works in other cells in the body, and in mouse embryos, Dr. Mitalipov said.

Instead, the male gene copied the healthy sequence from the female gene. The authors don’t know why it happened.

Maybe human sex cells or gametes evolved to repair themselves because they are the only cells that transmit genes to offspring and “need special protection,” said Juan Carlos Izpisua Belmonte, a co-author and geneticist at the Salk Institute.

Out of 54 embryos, 36 emerged mutation-free, a significant improvement over natural circumstances in which about half would not have the mutation. Another 13 embryos also emerged without the mutation, but not in every cell.

The researchers tried to eliminate the problem by acting at an earlier stage, injecting the egg with the sperm and CRISPR-Cas9 simultaneously, instead of waiting to inject CRISPR-Cas9 into the already fertilized egg.

That resulted in 42 of 58 embryos, 72 percent, with two mutation-free copies of the gene in every cell. They also found no unwanted mutations in the embryos, which were destroyed after about three days.

The method was not perfect. The remaining 16 embryos had unwanted additions or deletions of DNA. Dr. Mitalipov said he believed fine-tuning the process would make at least 90 percent of embryos mutation-free.

And for disease-causing mutations on maternal genes, the same process should occur, with the father’s healthy genetic sequence being copied, he said.

But the technique will not work if both parents have two defective copies. Then, scientists would have to determine how to coax one gene to copy a synthetic DNA sequence, Dr. Mitalipov said.

Otherwise, he said, it should work with many diseases, “a variety of different heritable mutations.”
R. Alta Charo, a bioethicist at University of Wisconsin at Madison, who led the committee with Dr. Hynes, said the new discovery could also yield more information about causes of infertility and miscarriages.

She doubts a flood of couples will have “edited children.”

“Nobody’s going to do this for trivial reasons,” Dr. Charo said. “Sex is cheaper and it’s more fun than IVF, so unless you’ve got a real need, you’re not going to use it.”

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Scientists find key ‘friendliness’ genes that distinguish dogs from wolves

Mira Abed

Your dog is basically a super social wolf, and scientists may have found the gene that makes him want to cuddle with you.

A new study shows that friendliness in dogs is associated with the same genes that make some people hyper-social.

The study found that structural variations in three genes on chromosome 6 are correlated with how much canines socialize with humans. An analysis of DNA from two dozen animals revealed that these genes look very different in dogs than they do in wolves.

Mutations in the same genes are also linked with a rare developmental disorder in humans called Williams-Beuren Syndrome, or WBS. People with WBS are typically hyper-social, meaning they form bonds quickly and show great interest in other people, including strangers. Other symptoms include developmental and learning disabilities as well as cardiovascular problems.

To Bridgett vonHoldt, who studies canine genetics at Princeton University, some of these traits sounded a lot like the behaviors of domesticated dogs, especially compared with wolves.

For example, dogs like to stay close to humans and gaze at them for longer periods of time than wolves do. Dogs also tend to be less independent in problem-solving when they’re around people, and they retain their affinity for humans throughout their lives.

“Many dogs maintain their puppy-like enthusiasm for social interactions throughout their life, whereas wolves grow out of this behavior and engage in more mature, abbreviated greetings as they age,” said Monique Udell, who studies animal behavior at Oregon State University and co-authored the new study. “One might think of how a young child greets you versus a teenager or adult relative.”

These behaviors are typical of what scientists call domestication syndrome, and researchers have noticed them in other kinds of domesticated animals as well. But they don’t fully understand how the underlying genetic changes develop.

“Everyone wants to find the genes that make dogs different from wolves, and try to understand how domestication changed the genome,” vonHoldt said.

She already had a head start. In 2010, as part of her doctoral research, vonHoldt had mapped the entire genome of 225 gray wolves and 912 dogs from 85 breeds. There were a few genes that stood out as consistently different between dogs and wolves, especially the WBS gene WBSCR17. But vonHoldt still didn’t have a handle on how those genetic differences were related to behavior.

VonHoldt met Udell three years ago, and they started chatting about canines. Together they realized that if they combined vonHoldt’s genetic expertise with Udell’s canine behavior data, they might be able to find the missing link.

They decided to examine the social behavior of a group of dogs and a group of wolves and then analyze their DNA in the region that included the WBSCR17 gene.

This idea was pretty new. While scientists have analyzed the genes responsible for specific clinical disorders in dogs, something as complex and varied as social behavior is a lot trickier to study.

After selecting 18 dogs and 10 gray wolves who had been socialized with humans, they began their work with a series of behavioral tests.

When the dogs were given a puzzle box with a sausage hidden inside, only two of the 18 were able to open the box whether or not a human was present. Wolves performed much better: eight of the 10 opened the box when a human was present, and nine of them opened the box when they were left alone.

When dogs were in the presence of a human, they spent a median of 20% of their time looking at the person and only 10% of the time looking at the box. The wolves, on the other hand, spent nearly 100% of the time looking at the box whether or not a human was present.

Udell said that these results agreed with previous studies that have shown that dogs are not as good at independent problem-solving as wolves, and that they get more distracted by social stimulation.

Next came the sociability test, which took place in four phases. In each, a human sat in a chair near a dog or a wolf for two minutes, and researchers recorded how much time the canine in question spent within 1 meter of the person.

In the first round, the person was a stranger who sat passively in the chair, not making eye contact or speaking to the animal. In the second round, the stranger actively engaged with the canine. Then the two phases were repeated with an owner or caretaker instead of a stranger.

The researchers determined that when familiar humans were present, dogs spent a median of 93% of their time near people while wolves spent only 36% of theirs. When the humans were strangers, the dogs stuck around 53% of the time and wolves 28%. This difference was not statistically significant and could have been due to chance.

While there was some variation between individual dogs and individual wolves, what was really important to the researchers was to determine whether there was a link between the sociability of each canine and what his or her DNA looked like.

So they took blood samples from 16 of the dogs and eight of the wolves and analyzed a large chunk of DNA on chromosome 6, including the region associated with WBS. (Two of the dogs and two of the wolves were not included in this part of the study.)

They found mutations in three genes that were much more common in the hyper-social canines, most of which were dogs. These three genes are called GTF2I, GTF2IRD1 and WBSCR17, and have also been shown to cause an increase in social behavior in mice and are believed to do the same in humans.

Interestingly, two of the wolves were very social and dog-like in their behavior, while one of the dogs acted quite wolf-like. The team found that the two social wolves had more mutations in these three genes, while the wolf-like dog had fewer mutations.

Adam Miklósi, an ethologist at Eötvös Loránd University in Hungary, said that the results would have been more convincing with a larger sample size.

The study authors acknowledged that their sample size was small, but they pointed out that the link between DNA and behavior was quite distinct. “I think it’s astounding that we have significance,” vonHoldt said.

Despite the difficulty in finding human-socialized wolves to use as subjects, the authors said they would like to study larger samples in the future. They also want to understand how this trend varies by dog breed.

VonHoldt is especially curious about exactly how the genetic mutations result in increased social behavior, and plans to research that question in more detail.

Eventually, she may figure out how wolves evolved into man’s best friend.

Ravens Surprise Scientists By Showing They Can Plan

A raven flies in the Seedskadee National Wildlife Refuge in Wyoming.

Tom Koerner/U.S. Fish and Wildlife Service

As recently as 10 years ago, humans were thought to be the only species with the ability to plan.

Recent studies on great apes showed the ability is not uniquely human. Now, scientists in Sweden have come to the surprising conclusion that ravens can also deliberately prepare for future events.

“It is conservative to conclude that ravens perform similarly to great apes and young children,” the researchers write. However, monkeys have failed similar experiments.

We’ve known that ravens, and other members of the corvid family, are smart. Previously, they were shown to think ahead by caching food to eat later.

But some scientists argued that food caching was not proof of an ability to plan because the birds could simply be biologically wired to do so, cognitive zoologist Can Kabadayi from Lund University tells The Two-Way.

So, Kabadayi and co-author Mathias Osvath set up a series of experiments to see if five ravens could flexibly plan during tasks that they don’t do in the wild: using tools and bartering. These are similar to studies done on great apes. Their findings were published today in the journal Science.

The researchers trained the birds how to use a simple tool, a rock, which could be used to open a box containing a treat (a piece of dog food) if the birds dropped it through a small tube.

They then tested whether the birds could pick the right tool from a series of “distracter” objects – such as a wheel, a ball, a metal pipe and a toy car – then save it and use it later to open the box.

One version of the experiment had a delay of 15 minutes between selecting an object and being presented with the reward box, and the ravens succeeded 86 percent of the time. The second extended that period to 17 hours, and the success rate was even higher, at 88 percent.

The birds were also trained to use a specific token to barter with a human for a food reward. Then, a different experimenter offered them a tray with the token on it along with other distracter objects. “When the ravens knew that trading would only happen on the next day, they chose and stored these tokens as soon as they were offered to them,” scientists Markus Boeckle and Nicola S. Clayton wrote in a separate Science paper on the Lund University research.

The researchers found that the birds would tend to opt out of immediate food rewards because of the promise of a larger, tastier treats later.

They were more likely to be willing to endure delayed gratification when they only had to wait a few seconds, rather than minutes for the larger treat – which is also a key component of human decision making. “We basically found that the further ahead in the future a reward for ravens, the less value it gets,” says Kabadayi.

It’s safe to say that ravens and mammals have not inherited planning skills through a common ancestor, says Kabadayi – they last shared an ancestor about 320 million years ago.

To plan, “you need a lot of different skill sets to work together and that’s interesting, because how can that be similar between corvids and great apes given they are so different to each other evolutionarily?” says Kabadayi. The skills likely evolved independently, through convergent evolution, he says.

Why would ravens develop the ability to plan? Kabadayi says there are many different theories.

He says this kind of complex cognition may have developed in reaction to ravens’ complex social hierarchy – for example, they would need to remember previous interactions with other birds, which could contribute to memory and planning skills. However, he says there are many other hierarchical species that don’t have planning abilities.

Factors like environmental pressures or the fact that they are scavengers competing with each other could also contribute, he says. The sheer density of neurons in a bird’s brain, even though it is small compared to apes, might also play a role.

Kabadayi says that scientists would need to test a large number of species for their abilities to plan, and see how this correlates with the possible explanations.

Parrots would be interesting to test next, he says, because they have a “huge number of neurons in their brains” and have been shown to have good memories.

Strange ‘sea pickles’ keep washing ashore in the Pacific Northwest — and scientists are baffled

There are strange sea creatures known as “sea pickles” invading the Pacific Northwest.

These gelatinous and somewhat translucent organisms, called pyrosomes, have been seen congregating, sometimes by the thousands, close to shore from Northern California up to southeast Alaska — clogging fishing nets and washing up on beaches, according to the National Oceanic and Atmospheric Administration. Experts say that this year, the critters are appearing in very high numbers outside the normal range of the species.

Most recently, NBC Bay Area reported that the sea dwellers have been causing a stir in Monterey Bay, frustrating fishermen trying to catch salmon and shrimp.

So what are pyrosomes, where did they come from, and why are they swarming shores?

NOAA Fisheries described them this way:

Pyrosomes are pelagic Tunicates, which are part of Chordata, a phylum that includes humans. It is tough and slimy to the touch with small, pronounced bumps. Inside the wall of this gelatinous tube, which can get up to 60 cm, individual zooids are tightly packed together. These zooids have an incurrent and excurrent siphon and use cilia to pump water for feeding, respiration and movement. Using a mucus net, they filter water for small planktonic microorganisms.

Pyrosomes are known to aggregate in large clusters at the surface and the zooids bioluminesce to create beautiful light displays.

Experts say pyrosomes are found all over the world, typically in warmer tropical waters far offshore.

Ric Brodeur, a research biologist at the NOAA’s Northwest Fisheries Science Center in Newport, Ore., said that beachcombers in Oregon have been walking the beaches there for decades, but he has started getting reports of pyrosomes washing up on the beaches only in the past few months. He has also been going to sea on research cruises since the 1980s and saw his first pyrosome only in 2014. He believes the high abundance is related to unusually warm ocean conditions along the coast that resembles pyrosomes’ normal habitat.

Brodeur said it is too soon to say whether pyrosomes will become permanent residents of the Pacific Northwest, as the ocean could revert to colder conditions.

“We’ll have to wait to see how it goes, but certainly, it’s not a good sign for the ecosystem to have these critters out there instead of the normal fish and crustacean prey most fish, birds and mammals off our coast are accustomed to,” he said.

During research cruises in February and May, pyrosomes — some more than two feet long — were seen in the highest number 40 to 200 miles off the Oregon Coast.

“A five-minute midwater tow of a research net off the Columbia River in late May brought up approximately 60,000 pyrosomes,” NOAA’s Northwest Fisheries Science Center said in a blog post. “Scientists spent hours sorting through the massive catch to find the rare fish they were targeting.”

Researchers from NOAA Fisheries, along with researchers from Oregon State University and the University of Oregon, have been studying these sea creatures to learn more about them.

Read more:

Dutch fishermen caught a rare two-headed sea creature. What happened next would horrify scientists.

This impossibly cute sea creature looks like a googly-eyed cartoon octopus

This deep sea creature looks just like the Flying Spaghetti Monster

Scientists Now Claim They Can Erase Memories and Implant Fake Ones

Huge Alzheimer’s breakthrough stuns scientists

Huge Alzheimer’s breakthrough stuns scientists

Scientists have just made a massive discovery that could have major implications for fighting dementia in old age.

Scientists have just made what could be the most important discovery about brains in a very long time, as the National Academies of Sciences, Engineering and Medicine said in a report released this past week that exercise, controlling blood pressure, and some brain training may be the magic formula to preventing mental decline, Alzheimer’s or dementia in old age.

While there are no proven ways to keep this mental deterioration from happening, this new report is an exciting indication that we may have more power to stop cognitive decline than we think. However, the government will need to do more research before such strategies are pushed as a viable method for ordinary citizens.

At the very least, these three strategies appear to do no harm, and at least two are really good for you even if they ultimately don’t work for preventing dementia. The report is based on a belief that changes in the brain begin long before symptoms of Alzheimer’s and other diseases, and it’s possible to catch the disease early on.

Cognitive training, blood pressure management for people with hypertension, and increased physical activity all show modest but inconclusive evidence that they can help prevent cognitive decline and dementia, but there is insufficient evidence to support a public health campaign encouraging their adoption, says a new report from the National Academies of Sciences, Engineering, and Medicine. Additional research is needed to further understand and gain confidence in their effectiveness, said the committee that conducted the study and wrote the report.

“There is good cause for hope that in the next several years much more will be known about how to prevent cognitive decline and dementia, as more clinical trial results become available and more evidence emerges,” said Alan I. Leshner, chair of the committee and CEO emeritus, American Association for the Advancement of Science. “Even though clinical trials have not conclusively supported the three interventions discussed in our report, the evidence is strong enough to suggest the public should at least have access to these results to help inform their decisions about how they can invest their time and resources to maintain brain health with aging.”

An earlier systematic review published in 2010 by the Agency for Healthcare Research and Quality (AHRQ) and an associated “state of the science” conference at the National Institutes of Health had concluded that there was insufficient evidence to make recommendations about any interventions to prevent cognitive decline and dementia. Since then, understanding of the pathological processes that result in dementia has advanced significantly, and a number of clinical trials of potential preventive interventions have been completed and published. In 2015, the National Institute on Aging (NIA) contracted with AHRQ to conduct another systematic review of the current evidence. NIA also asked the National Academies to convene an expert committee to help inform the design of the AHRQ review and then use the results to make recommendations to inform the development of public health messaging, as well as recommendations for future research. This report examines the most recent evidence on steps that can be taken to prevent, slow, or delay the onset of mild cognitive impairment and clinical Alzheimer’s-type dementia as well as steps that can delay or slow age-related cognitive decline.

Overall, the committee determined that despite an array of advances in understanding cognitive decline and dementia, the available evidence on interventions derived from randomized controlled trials – considered the gold standard of evidence – remains relatively limited and has significant shortcomings. Based on the totality of available evidence, however, the committee concluded that three classes of interventions can be described as supported by encouraging but inconclusive evidence. These interventions are:

cognitive training – which includes programs aimed at enhancing reasoning and problem solving, memory, and speed of processing – to delay or slow age-related cognitive decline. Such structured training exercises may or may not be computer-based. blood pressure management for people with hypertension – to prevent, delay, or slow clinical Alzheimer’s-type dementia. increased physical activity – to delay or slow age-related cognitive decline.

Cognitive training has been the object of considerable interest and debate in both the academic and commercial sectors, particularly within the last 15 years. Good evidence shows that cognitive training can improve performance on a trained task, at least in the short term. However, debate has centered on evidence for long-term benefits and whether training in one domain, such as processing speed, yields benefits in others, such as in memory and reasoning, and if this can translate to maintaining independence in instrumental activities of daily living, such as driving and remembering to take medications. Evidence from one randomized controlled trial suggests that cognitive training delivered over time and in an interactive context can improve long-term cognitive function as well as help maintain independence in instrumental activities of daily living for adults with normal cognition. However, results from other randomized controlled trials that tested cognitive training were mixed.

Managing blood pressure for people with hypertension, particularly during midlife – generally ages 35 to 65 years – is supported by encouraging but inconclusive evidence for preventing, delaying, and slowing clinical Alzheimer’s-type dementia, the committee said. The available evidence, together with the strong evidence for blood pressure management in preventing stroke and cardiovascular disease and the relative benefit/risk ratio of antihypertensive medications and lifestyle interventions, is sufficient to justify communication with the public regarding the use of blood pressure management, particularly during midlife, for preventing, delaying, and slowing clinical Alzheimer’s-type dementia, the report says.

It is well-documented that physical activity has many health benefits, and some of these benefits – such as stroke prevention – are causally related to brain health. The AHRQ systematic review found that the pattern of randomized controlled trials results across different types of physical activity interventions provides an indication of the effectiveness of increased physical activity in delaying or slowing age-related cognitive decline, although these results were not consistently positive. However, several other considerations led the committee to conclude that the evidence is sufficient to justify communicating to the public that increased physical activity for delaying or slowing age-related cognitive decline is supported by encouraging but inconclusive evidence.

None of the interventions evaluated in the AHRQ systematic review met the criteria for being supported by high-strength evidence, based on the quality of randomized controlled trials and the lack of consistently positive results across independent studies. This limitation suggests the need for additional research as well as methodological improvements in the future research. The National Institutes of Health and other interested organizations should support further research to strengthen the evidence base on cognitive training, blood pressure management, and increased physical activity, the committee said. Examples of research priorities for these three classes of interventions include evaluating the comparative effectiveness of different forms of cognitive training interventions; determining whether there are optimal blood pressure targets and approaches across different age ranges; and comparing the effects of different forms of physical activity.

When funding research on preventing cognitive decline and dementia, the National Institutes of Health and other interested organizations should identify individuals who are at higher risk of cognitive decline and dementia; increase participation of underrepresented populations; begin more interventions at younger ages and have longer follow-up periods; use consistent cognitive outcome measures across trials to enable pooling; integrate robust cognitive outcome measures into trials with other primary purposes; include biomarkers as intermediate outcomes; and conduct large trials designed to test the effectiveness of an intervention in broad, routine clinical practices or community settings.

The study was sponsored by the National Institute on Aging. The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine. The National Academies operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln.

These few things may help stave off dementia, scientists say

Scientists think there may be a few things you can do to keep dementia at bay: train your brain, keep your blood pressure under control and stay active.

According to a report published Thursday by the National Academies of Sciences, Engineering and Medicine (NASEM), there is promising evidence that cognitive training, managing your blood pressure if you have hypertension and increasing your physical activity may help prevent age-related cognitive decline and dementia.

The report’s findings line up with the Alzheimer’s Association’s findings from two years ago, said Keith N. Fargo, the association’s director of Scientific Programs and Outreach. In 2015, the organization published its own review and identified two things that could help minimize the risk of cognitive decline.

“They were increasing physical activity and improving cardiovascular health,” he said.

“The ideas were there before the report,” said Dan G. Blazer, a member of the NASEM committee that conducted the study and the J.P. Gibbons Professor of Psychiatry Emeritus at Duke University Medical Center. “What is good for the heart is good for the brain. Therefore, exercise and controlling high blood pressure are good for the brain.”

And cognitive training is getting a lot of attention now, said Blazer. Cognitive training refers to programs or exercises aimed at improving reasoning, problem-solving, memory and processing speed. Sometimes they can be computer-based.

In one randomized control trial of 2,832 participants that the committee reviewed called the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial, those who had received cognitive training in reasoning and speed-of-processing showed less decline in those areas than those who didn’t — after ten years.

“(Cognitive training) is an area worthy of looking forward,” said Blazer.

The evidence is encouraging, but not enough to embark on a public health campaign, said Alan I. Leshner, the chair of the NASEM committee and CEO Emeritus of the American Association for the Advancement of Science. In the report, the findings were described as “encouraging, but inconclusive” evidence.

Further research needs to be done, the report added.

Even so, Fargo of the Alzheimer’s Association said the public should understand one thing.

“There are things that you can do to reduce your risk,” he said.

“You can take your own cognitive health and brain health in your hands,” he said. “You can affect it in a positive way.”

Follow Sarah Toy on Twitter: @sarahtoy17

Scientists find 7.2-million-year-old pre-human remains in the Balkans

Scientists find 7.2-million-year-old pre-human remains in the Balkans
The lower jaw of the 7.175 million year old Graecopithecus freybergi (El Graeco) from Pyrgos Vassilissis, Greece (today in metropolitan Athens). Credit: Wolfgang Gerber, University of Tübingen

The common lineage of great apes and humans split several hundred thousand years earlier than hitherto assumed, according to an international research team headed by Professor Madelaine Böhme from the Senckenberg Centre for Human Evolution and Palaeoenvironment at the University of Tübingen and Professor Nikolai Spassov from the Bulgarian Academy of Sciences. The researchers investigated two fossils of Graecopithecus freybergi with state-of-the-art methods and came to the conclusion that they belong to pre-humans. Their findings, published today in two papers in the journal PLOS ONE, further indicate that the split of the human lineage occurred in the Eastern Mediterranean and not – as customarily assumed – in Africa.

Present-day chimpanzees are humans’ nearest living relatives. Where the last chimp-human common ancestor lived is a central and highly debated issue in palaeoanthropology. Researchers have assumed up to now that the lineages diverged five to seven million years ago and that the first pre-humans developed in Africa. According to the 1994 theory of French palaeoanthropologist Yves Coppens, climate change in Eastern Africa could have played a crucial role. The two studies of the research team from Germany, Bulgaria, Greece, Canada, France and Australia now outline a new scenario for the beginning of human history.

Dental roots give new evidence

The team analyzed the two known specimens of the hominid Graecopithecus freybergi: a lower jaw from Greece and an upper premolar from Bulgaria. Using computer tomography, they visualized the internal structures of the fossils and demonstrated that the roots of premolars are widely fused.

“While great apes typically have two or three separate and diverging roots, the roots of Graecopithecus converge and are partially fused – a feature that is characteristic of modern humans, early humans and several pre-humans including Ardipithecus and Australopithecus“, said Böhme.

Scientists find 7.2-million-year-old pre-human remains in the Balkans
A 7.24 million year old upper premolar of Graecopithecus from Azmaka, Bulgaria. Credit: Wolfgang Gerber, University of Tübingen

The lower jaw, nicknamed ‘El Graeco’ by the scientists, has additional dental root features, suggesting that the species Graecopithecus freybergi might belong to the pre-human lineage. “We were surprised by our results, as pre-humans were previously known only from sub-Saharan Africa,” said Jochen Fuss, a Tübingen PhD student who conducted this part of the study.

Furthermore, Graecopithecus is several hundred thousand years older than the oldest potential pre-human from Africa, the six to seven million year old Sahelanthropus from Chad. The research team dated the sedimentary sequence of the Graecopithecus fossil sites in Greece and Bulgaria with physical methods and got a nearly synchronous age for both fossils – 7.24 and 7.175 million years before present. “It is at the beginning of the Messinian, an age that ends with the complete desiccation of the Mediterranean Sea,” Böhme said.

Professor David Begun, a University of Toronto paleoanthropologist and co-author of this study, added, “This dating allows us to move the human-chimpanzee split into the Mediterranean area.”

Environmental changes as the driving force for divergence

As with the out-of-East-Africa theory, the evolution of pre-humans may have been driven by dramatic environmental changes. The team led by Böhme demonstrated that the North African Sahara desert originated more than seven million years ago. The team concluded this based on geological analyses of the sediments in which the two fossils were found. Although geographically distant from the Sahara, the red-colored silts are very fine-grained and could be classified as desert dust. An analysis of uranium, thorium, and lead isotopes in individual dust particles yields an age between 0.6 and 3 billion years and infers an origin in Northern Africa.

Scientists find 7.2-million-year-old pre-human remains in the Balkans
An electron microscope image of a dust particle rounded by eolian transport. It originated in the Sahara desert and was found in 7.2 million year old sediments in Greece. Credit: Ulf Linnemann, Senckenberg Center for Human Evolution and Palaeoenvironment, University of Tübingen

Moreover, the dusty sediment has a high content of different salts. “These data document for the first time a spreading Sahara 7.2 million years ago, whose desert storms transported red, salty dusts to the north coast of the Mediterranean Sea in its then form,” the Tübingen researchers said. This process is also observable today. However, the researchers’ modelling shows that, with up to 250 grams per square meter and year, the amount of dust in the past considerably exceeds recent dust loadings in Southern Europe more than tenfold, comparable to the situation in the present-day Sahel zone in Africa.

Fire, grass, and water stress

The researchers further showed that, contemporary to the development of the Sahara in North Africa, a savannah biome formed in Europe. Using a combination of new methodologies, they studied microscopic fragments of charcoal and plant silicate particles, called phytoliths. Many of the phytoliths identified derive from grasses and particularly from those that use the metabolic pathway of C4-photosynthesis, which is common in today’s tropical grasslands and savannahs. The global spread of C4-grasses began eight million years ago on the Indian subcontinent – their presence in Europe was previously unknown.

“The phytolith record provides evidence of severe droughts, and the charcoal analysis indicates recurring vegetation fires,” said Böhme. “In summary, we reconstruct a savannah, which fits with the giraffes, gazelles, antelopes, and rhinoceroses that were found together with Graecopithecus,” Spassov added

“The incipient formation of a desert in North Africa more than seven million years ago and the spread of savannahs in Southern Europe may have played a central role in the splitting of the human and chimpanzee lineages,” said Böhme. She calls this hypothesis the North Side Story, recalling the thesis of Yves Coppens, known as East Side Story.

The findings are described in two studies pubished in PLOS ONE titled “Potential hominin affinities of Graecopithecus from the late Miocene of Europe” and “Messinian age and savannah environment of the possible hominin Graecopithecus from Europe.”

Scientists Identify 28,000 Medicinal Plants That Treat Ailments from Cancer to Diabetes

http://www.renegadetribune.com/scientists-identify-28000-medicinal-plants-treat-ailments-cancer-diabetes/
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In recent years, the term “plant medicine” has come to be associated with psychedelics like mushrooms and ayahuasca, which are increasingly documented to provide mental and emotional relief to users. But according to a recent analysis from Kew Gardens in the United Kingdom, there are over 28,000 other plants currently being used as medicine throughout the world.

The second annual report from Britain’s Royal Botanic Gardens at Kew, located in London, is the result of the research and analysis of 128 scientists from 12 countries around across the globe.

According to their findings, there are 28,187 plants “currently recorded as being of medicinal use.

The report [pdf] explains:

“In many regions of the world, people still rely on traditional plant-based medicines for their primary healthcare. This is especially true for many rural communities in Africa, parts of Asia, and Central and South America, where plants and knowledge of their traditional use are accessible and affordable. In other countries, many of these traditional plant-based medicines are being integrated through regulations into mainstream health systems.”

Though plant medicines are making their way into the mainstream, the researchers note that currently, just “16% (4,478) of the species used in plant-based medicines are cited in a medicinal regulatory publication.” Even so, they note data on drugs approved by the FDA and similar agencies:

“Since 1981, 1,130 new therapeutic agents have been approved for use as pharmaceutical drugs, of which 593 are based on compounds from natural sources. Thirty-eight are derived from medicinal plants. Fifteen of the 56 natural drugs registered for the treatment of cancer since 1980 are derived from medicinal plants with a long history of traditional use.”

They note, for example, that “The anti-cancerous drugs vincristine and vinblastine are derived from the Madagascar periwinkle, Catharanthus roseus in the Apocynaceae family.”

Additionally:

“For example drugs based on Paclitaxel have been isolated from the yew tree (Taxus spp.), Camptothecin from the happy tree, (Camptotheca acuminata) and Podophyllotoxin from the May apple (Podophyllum hexandrum and P. peltatum).”

Further, researchers have discovered over 1,000 species of beneficial plants since their survey last year. As Yahoo News summarized, “new plants discovered over the past year include nine species of a climbing vine used in the treatment of Parkinson’s disease.

The report said two plants, artemisinin and quinine, are ‘among the most important weapons’ against malaria, which killed over 400,000 people in 2015,” Yahoo summarized.

According to Monique Simmonds, deputy director of science at Kew, “The report is highlighting the huge potential that there is for plants, in areas like diabetes and malaria,” Yahoo reported. “One study documents 656 flowering plant species used traditionally for diabetes, representing 437 genera and 111 families,” the report explains.

It also points out that of “only five drugs developed specifically for the symptomatic treatment of Alzheimer’s disease, two are derived from plants.”

Some particularly powerful species of plants include Fabaceae (pea and bean), Lamiaceae (mint), Euphorbiaceae (spurge), Apocynaceae (dogbane), Malvaceae (mallow), Apiaceae (parsley or carrot), and Ranunculaceae (buttercup). Their key classes of compounds are alkaloids (Fabaceae), terpenes (Lamiaceae),  diterpenoids (Euphorbiaceae), cardiac-glycosides (Apocynaceae), organic acids (Malvaceae), coumarins (Apiaceae), and alkaloids (Ranunculaceae). Another highly useful plant documented in the report is Moraceae, which is used in the treatment of diabetes.

Though their report offers great promise, they highlight some pitfalls. Stressing that correct labeling of plant medicines is vital, they explain:

Product labeling is frequently misleading, with the trade name ‘ginseng’, for example, referring to 15 different species of plant, each with its own particular chemistry and therapeutic properties[10]. Substitution by a Belgian clinic of one Chinese medicinal herb (‘Fang Ji’) with another sharing the same name, led to over 100 patients requiring kidney dialysis for the remainder of their lives.”

They also point out the threat to the plants themselves.

Increasing demand for herbal medicines (particularly for species covered by pharmacopoeias) threatens wild populations of many of these plants,” they note, adding that “ the focus of world trade on relatively few species of medicinal plants leads to sustainability and conservation issues, which ultimately lead to other plants being substituted, with potential risks to human health.”

They advocate more precise scientific labeling of plants and more “clarity on which plants have or have not been studied in drug discovery programmes.”

Such approaches,” they contend, “will be hugely important in improving our ability to realise current and future medicinal benefits from plants.”

As pharmaceutical drugs continue to wreak hazardous consequences, the healing power of natural plants appears to hold great promise for humans seeking treatment without the chemical side effects of current popular medicines.


This article originally appeared on The Anti-Media.

No Bones About It: Scientists Recover Ancient DNA From Cave Dirt

Sifting through teaspoons of clay and sand scraped from the floors of caves, German researchers have managed to isolate ancient human DNA — without turning up a single bone.

Their new technique, described in a study published on Thursday in the journal Science, promises to open new avenues of research into human prehistory and was met with excitement by geneticists and archaeologists.

“It’s a bit like discovering that you can extract gold dust from the air,” said Adam Siepel, a population geneticist at Cold Spring Harbor Laboratory.

“An absolutely amazing and exciting paper,” added David Reich, a genetics professor at Harvard who focuses on ancient DNA.

Until recently, the only way to study the genes of ancient humans like the Neanderthals and their cousins, the Denisovans, was to recover DNA from fossil bones.

But they are scarce and hard to find, which has greatly limited research into where early humans lived and how widely they ranged. The only Denisovan bones and teeth that scientists have, for example, come from a single cave in Siberia.

Looking for these genetic signposts in sediment has become possible only in the last few years, with recent developments in technology, including rapid sequencing of DNA.

An entrance to the archaeological site of Chagyrskaya Cave, Russia. The only Denisovan bones and teeth that scientists have come from a single cave in Siberia.CreditRichard G. Roberts

Although DNA sticks to minerals and decayed plants in soil, scientists did not know whether it would ever be possible to fish out gene fragments that were tens of thousands of years old and buried deep among other genetic debris.

Bits of genes from ancient humans make up just a minute fraction of the DNA floating around in the natural world.

But the German scientists, led by Matthias Meyer at the Max Planck Institute for Developmental Biology in Tübingen, have spent years developing methods to find DNA even where it seemed impossibly scarce and degraded.

“There’s been a real revolution in technology invented by this lab,” Dr. Reich said. “Matthias is kind of a wizard in pushing the envelope.”

Scientists began by retrieving DNA from ancient bones: first Neanderthals, then Denisovans.

To identify the Denisovans, Svante Paabo, a geneticist at the Planck Institute and a co-author of the new paper, had only a child’s pinkie bone to work with.

His group surprised the world in 2010 by reporting that it had extracted DNA from the bone, finding that it belonged to a group of humans distinct from both Neanderthals and modern humans.

But that sort of analysis is limited by the availability of fossil bones.

“In a lot of cases, you can get bones, but not enough,” said Hendrik Poinar, an evolutionary geneticist at McMaster University.

“If you just have one small piece of bone from one site, curators do not want you to grind it up.”

Finding and analyzing ancient DNA in dirt is far more difficult than getting it out of bone. The idea was not new, noted Viviane Slon, a member of Dr. Meyer’s group and the first author of the new paper.

Other groups of researchers have found DNA in sediment, including Dr. Poinar and Michael Hofreiter, his former student. Using a tablespoon of dirt from a cave in Colorado, his team discovered traces from 16 animal species that had lived there. It took two weeks to do it.

Researchers who had scoured that cave for bones had spent 20 years there and had sifted through two metric tons of dirt to find bones, teeth or skin of 20 animal species — including the 16 that Dr. Poinar’s group later identified.

The new study involved searching for ancient DNA in four caves in Eurasia where humans were known to have lived between 14,000 and 550,000 years ago.

Dr. Meyer and his colleagues figured out which DNA in the cave sediment was prehistoric by looking for telltale signs of degradation at the ends of the molecules.

They then plucked out DNA from Neanderthals and Denisovans by using molecular hooks to snare genes in mitochondria — the cells’ energy factories — that are unique to these humans.

The scientists also built a robotic system to analyze the samples quickly; the old way, pipetting by hand, required several days to analyze only a fraction as many samples.

The group needed that efficiency. From different dirt samples, they recovered between 5,000 and 2.8 million DNA fragments. The number of DNA fragments per sample that were from ancient humans was minuscule and ranged from 0 to 8,822, depending on the site in the cave.

Svante Paabo, a geneticist at the Planck Institute and a co-author of the new paper, showing the location of a sediment sample collected from a layer where a 560,000-year-old human tooth was discovered in 2015.CreditChristian Perrenoud

The discovery that it is now possible to do all this, Dr. Reich said, is just “an amazing, amazing thing.” The questions that can now be addressed seem almost endless.

Researchers could feasibly begin searching for bones in caves where DNA in the dirt indicates habitation by ancient humans. And they are likely to begin learning much more about human prehistory.

The Denisovans, for example: Tiny pieces of genes inherited from them have been found in modern humans in Papua New Guinea. How did they get there? And why these people, and not humans closer to Siberia?

With the new technique, one way to try to verify the presence of humans would be to look for ancient human DNA at the site where the bones were found or in areas nearby.

“A natural thing to do is start looking in sediments,” said Jonathan Pritchard, a professor of genetics and biology at Stanford.

Another application of the discovery, said Dr. Reich, would be to start looking for evidence of ancient human DNA in open air sites, instead of looking for bones in caves.

“If it worked, it would provide a much richer picture of the geographic distribution and migration patterns of ancient humans, one that was not limited by the small number of bones that have been found,” he said.

“That would be a magical thing to do.”