Oct 5, 2019

Children told lies by parents subsequently lie more as adults, face adjustment difficulty

Parent scolding child concept.
"If you don't behave, I'll call the police," is a lie that parents might use to get their young children to behave. Parents' lies elicit compliance in the short term, but a new psychology study led by Nanyang Technological University, Singapore (NTU Singapore) suggests that they are associated with detrimental effects when the child becomes an adult.

The research team asked 379 Singaporean young adults whether their parents lied to them when they were children, how much they lie to their parents now, and how well they adjust to adulthood challenges.

Adults who reported being lied to more as children, were more likely to report lying to their parents in their adulthood. They also said they faced greater difficulty in meeting psychological and social challenges. Adjustment difficulties include disruptiveness, conduct problems, experience of guilt and shame, as well as selfish and manipulative character.

The research, done in collaboration with Canada's University of Toronto, the United States' University of California, San Diego, and China's Zhejiang Normal University, was published in the Journal of Experimental Child Psychology in September.

Lead author Assistant Professor Setoh Peipei from NTU Singapore's School of Social Sciences said, "Parenting by lying can seem to save time especially when the real reasons behind why parents want children to do something is complicated to explain. When parents tell children that 'honesty is the best policy', but display dishonesty by lying, such behaviour can send conflicting messages to their children. Parents' dishonesty may eventually erode trust and promote dishonesty in children."

"Our research suggests that parenting by lying is a practice that has negative consequences for children when they grow up. Parents should be aware of these potential downstream implications and consider alternatives to lying, such as acknowledging children's feelings, giving information so children know what to expect, offering choices and problem-solving together, to elicit good behaviour from children."

How the study was done

379 Singaporean young adults completed four online questionnaires.

The first questionnaire asked participants to recall if their parents told them lies that related to eating; leaving and/or staying; children's misbehaviour; and spending money. Some examples of such lies are "If you don't come with me now, I will leave you here by yourself" and "I did not bring money with me today, we can come back another day."

The second questionnaire asked participants to indicate how frequently as adults they lied to their parents. It asked about lies in relation to their activities and actions; prosocial lies (or lies intended to benefit others); and exaggerations about events.

Lastly, participants filled in two questionnaires that measured their self-reported psychosocial maladjustment and tendency to behave selfishly and impulsively.

The analysis found that parenting by lying could place children at a greater risk of developing problems that the society frowns upon, such as aggression, rule-breaking and intrusive behaviours.

Some limitations of the study include relying on what young adults report about their retrospective experience of parents' lying. "Future research can explore using multiple informants, such as parents, to report on the same variables," suggested Asst Prof Setoh.

The authors also pointed out that as the study is correlational in design, which aims to find out the naturally occurring relationships between variables, they are unable to draw causal inferences.

Another area yet to be investigated would be the nature of the lies or goals of the parent. Asst Prof Setoh said, "It is possible that a lie to assert the parents' power, such as saying 'If you don't behave, we will throw you into the ocean to feed the fish', may be more related to children's adjustment difficulties as adults, compared to lies that target children's compliance, e.g. 'there is no more candy in the house'.

"Authority assertion over children is a form of psychological intrusiveness, which may undermine children's sense of autonomy and convey rejection, ultimately undermining children's emotional well-being. Future research should examine the nature of the lies and goals of the parents so that researchers can suggest what kind of lies to avoid, and what kind of truth-telling parents should engage in."

Read more at Science Daily

Aspirin may halve air pollution harms

Aspirin pills
A new study is the first to report evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin may lessen the adverse effects of air pollution exposure on lung function. The team of researchers from the Columbia Mailman School of Public Health, Harvard Chan School of Public Health, Boston University School of Medicine published their findings in the American Journal of Respiratory and Critical Care Medicine.

The researchers analyzed a subset of data collected from a cohort of 2,280 male veterans from the greater Boston area who were given tests to determine their lung function. The average age of participants was 73 years. The researchers examined the relationship between test results, self-reported NSAID use, and ambient particulate matter (PM) and black carbon in the month preceding the test, while accounting for a variety of factors, including the health status of the subject and whether or not he was a smoker. They found that the use of any NSAID nearly halved of the effect of PM on lung function, with the association consistent across all four weekly air pollution measurements from same-day to 28 days prior to the lung function test.

Because most of the people in the study cohort who took NSAIDs used aspirin, the researchers say the modifying effect they observed was mainly from aspirin, but add that effects of non-aspirin NSAIDs are worthy of further exploration. While the mechanism is unknown, the researchers speculate that NSAIDs mitigate inflammation brought about by air pollution.

"Our findings suggest that aspirin and other NSAIDs may protect the lungs from short-term spikes in air pollution," says first and corresponding author Xu Gao, PhD, a post-doctoral research scientist in the Department of Environmental Health Sciences at the Columbia Mailman School. "Of course, it is still important to minimize our exposure to air pollution, which is linked to a host of adverse health effects, from cancer to cardiovascular disease."

"While environmental policies have made considerable progress toward reducing our overall exposure to air pollution, even in places with low levels of air pollution, short-term spikes are still commonplace," says senior author Andrea Baccarelli, MD, PhD, chair of the Department of Environmental Health Sciences at the Columbia Mailman School. "For this reason, it is important to identify means to minimize those harms."

An earlier study by Baccarelli found that B vitamins may also play a role in reducing the health impact of air pollution.

Read more at Science Daily

Oct 4, 2019

A filament fit for space: Silk is proven to thrive in outer space temperatures

Their initial discovery had seemed like a contradiction because most other polymer fibres embrittle in the cold. But after many years of working on the problem, the group of researchers have discovered that silk's cryogenic toughness is based on its nano-scale fibrills. Sub-microscopic order and hierarchy allows a silk to withstand temperatures of down to -200oC. And possibly even lower, which would make these classic natural luxury fibres ideal for applications in the depths of chilly outer-space.

The interdisciplinary team examined the behaviour and function of several animal silks cooled down to liquid nitrogen temperature of -196 oC. The fibres included spider silks but the study focused on the thicker and much more commercial fibres of the wild silkworm Antheraea pernyi.

In an article published today in Materials Chemistry Frontiers, the team was able to show not only 'that' but also 'how' silk increases its toughness under conditions where most materials would become very brittle. Indeed, silk seems to contradict the fundamental understanding of polymer science by not losing but gaining quality under really cold conditions by becoming both stronger and more stretchable. This study examines the 'how' and explains the 'why'. It turns out that the underlying processes rely on the many nano-sized fibrils that make up the core of a silk fibre.

In line with traditional polymer theory, the study asserts that the individual fibrils do indeed become stiffer as they get colder. The novelty and importance of the study lies in the conclusion that this stiffening leads to increased friction between the fribrils. This friction in turn increases crack-energy diversion while also resisting fibril slippage. Changing temperature would also modulate attraction between individual silk protein molecules in turn affecting core properties of each fibril, which is made up from many thousand molecules.

Importantly, the research is able to describe the toughening process on both the micron and nano-scale levels. The team concludes that any crack that tears through the material is diverted each time it hits a nano-fibril forcing it to lose ever more energy in the many detours it has to negotiate. And thus a silk fibre only breaks when the hundreds or thousands of nano-fibrils have first stretched and then slipped and then all of them have individually snapped.

The discovery is pushing boundaries because it studied a material in the conceptually difficult and technologically challenging area that not only spans the micron and nano-scales but also has to be studied at temperatures well below any deep-freezer. The size of scales studied range from the micron size of the fibre to the sub-micron size of a filament bundle to the nano-scale of the fibrils and last but not least to the level supra-molecular structures and single molecules. Against the backdrop of cutting edge science and futuristic applications it is worth remembering that silk is not only 100% a biological fibre but also an agricultural product with millennia of R&D.

It would appear that this study has far-reaching implications by suggesting a broad spectrum of novel applications for silks ranging from new materials for use in Earth's polar regions to novel composites for light-weight aeroplanes and kites flying in the strato- and meso-sphere to, perhaps, even giant webs spun by robot spiders to catch astro-junk in space.

Professor Fritz Vollrath, from Oxford University's Department of Zoology, said: 'We envision that this study will lead to the design and fabrication of new families of tough structural filaments and composites using both natural and silk-inspired filaments for applications in extreme cold conditions such as space.'

Prof Zhengzhong Shao, from the Macromolecular Science Department of Shanghai's Fudan University, said: 'We conclude that the exceptional mechanical toughness of silk fibre at cryogenic temperatures derives from its highly aligned and oriented, relatively independent and extensible nanofibrillar morphology.'

Dr Juan Guan from Beihang University, in Beijing, said: 'This study provides novel insights into our understanding of the structure-property relationships of natural high-performance materials which we hope will lead to fabricating human-made polymers and composites for low temperature and high impact applications.'

And Dr Chris Holland from Sheffield University, leader of a European-wide Research Consortium on novel, sustainable bio-fibres based on insights into natural silk spinning said: 'Natural silks continue to prove themselves as gold standard materials for fibre production. The work here identifies that it is not just the chemistry, but how silks are spun and in consequence are structured that is the secret to their success.'

Read more at Science Daily

Researchers unlock potential to use CRISPR to alter the microbiome

Researchers at Western University have developed a new way to deliver the DNA-editing tool CRISPR-Cas9 into microorganisms in the lab, providing a way to efficiently launch a targeted attack on specific bacteria.

Published today in Nature Communications, this study opens up the possibility of using CRISPR to alter the makeup of the human microbiome in a way that could be personalized and specific from person to person. It also presents a potential alternative to traditional antibiotics to kill bacteria like Staphyloccous aureus (Staph A) or Escherichia coli (E. coli).

"One of the major reasons that I am excited about this work is that it has a wide range of possible real-world applications," said Bogumil Karas, PhD, Assistant Professor at Western's Schulich School of Medicine & Dentistry. "It has the potential for development of next generation antimicrobial agents that would be effective even for bacteria that are resistant to all known antibiotics. This technology could also be used to help 'good' bacteria produce compounds to treat diseases caused by protein deficiencies."

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats and can be programmed to target specific stretches of genetic code and to edit DNA at precise locations. Researchers use CRISPR to permanently modify genes in living cells and organisms.

In this way, CRISPR can be programmed to kill bacteria, but until now there wasn't a way to efficiently and specifically target certain bacterial strains.

"Using CRISPR to kill things isn't a new idea because that's what CRISPR does naturally," said David Edgell, PhD, Professor at Schulich Medicine & Dentistry. "The problem has always been how you get CRISPR to where you want it to go. Other delivery systems could only go to a few spots, where ours can go anywhere."

The delivery system developed at Western uses bacteria's natural ability to replicate -- called bacterial conjugation -- to deliver CRISPR to specific bacteria, in order to alter its DNA and kill it.

"Specific delivery of any therapeutic agent, including CRISPR, is usually one of the biggest bottlenecks in development of new treatments. By developing this new delivery system, we created new tools that could help us in the development of more effective therapies in the near future," said Karas.

The team says their delivery system is not only broadly applicable, but it is also more efficient than previous systems.

Read more at Science Daily

Rare view into the formation of viruses

For the first time, researchers have captured images of the formation of individual viruses, offering a real-time view into the kinetics of viral assembly. The research provides new insights into how to fight viruses and engineer self-assembling particles.

The research is published in the Proceedings of the National Academy of Sciences.

"Structural biology has been able to resolve the structure of viruses with amazing resolution, down to every atom in every protein," said Vinothan Manoharan, the Wagner Family Professor of Chemical Engineering and Professor of Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences. "But we still didn't know how that structure assembles itself. Our technique gives the first window into how viruses assemble and reveals the kinetics and pathways in quantitative detail."

Manoharan is also co-director of the Quantitative Biology Initiative, a cross-Harvard effort that brings together biology, novel measurement techniques, statistics and mathematics to develop causal, predictive mathematical models of biological systems.

Manoharan and his team focused on single-stranded RNA viruses, the most abundant type of virus on the planet. In humans, RNA viruses are responsible for, among others, West Nile fever, gastroenteritis, hand, foot, and mouth disease, polio, and the common cold.

These viruses tend to be very simple. The virus Manoharan and his team studied, which infects E. coli bacteria, is about 30 nanometers in diameter and has one piece of RNA, with about 3600 nucleotides, and 180 identical proteins. The proteins arrange themselves into hexagons and pentagons to form a soccer-ball-like structure around the RNA, called a capsid.

How those proteins manage to form that structure is the central question in virus assembly. Until now, no one had been able to observe viral assembly in real time because viruses and their components are very small and their interactions are very weak.

To observe the viruses, the researchers used an optical technique known as interferometric scattering microscopy, in which the light scattered off an object creates a dark spot in a larger field of light. The technique doesn't reveal the virus's structure but it does reveal its size and how that size changes with time.

The researchers attached viral RNA strands to a substrate, like stems of a flower, and flowed proteins over the surface. Then, using the interferometric microscope, they watched as dark spots appeared and grew steadily darker until they were the size of full-grown viruses. By recording intensities of those growing spots, the researchers could actually determine how many proteins were attaching to each RNA strand over time.

"One thing we noticed immediately is that the intensity of all the spots started low and then shot up to the intensity of a full virus," Manoharan said. "That shooting up happened at different times. Some capsids assembled in under a minute, some took two or three, and some took more than five. But once they started assembling, they didn't backtrack. They grew and grew and then they were done."

The researchers compared these observations to previous results from simulations, which predicted two types of assembly pathways. In one type of pathway, the proteins first stick randomly to the RNA and then rearrange themselves into a capsid. In the second, a critical mass of proteins, called a nucleus, must form before the capsid can grow.

The experimental results matched the second pathway and ruled out the first. The nucleus forms at different times for different viruses but once it does, the virus grows quickly and doesn't stop until it reaches its right size.

The researchers also noticed that the viruses tended to misassemble more often when there were more proteins flowing over the substrate.

"Viruses that assemble in this way have to balance the formation of nuclei with the growth of the capsid. If nuclei form too quickly, complete capsids can't grow. That observation might give us some insights into how to derail the assembly of pathogenic viruses," said Manoharan.

How the individual proteins come together to form the nucleus is still an open question but now that experimentalists have identified the pathway, researchers can develop new models that explore assembly within that pathway. Those models might also be useful for designing nanomaterials that assemble themselves.

"This is a good example of quantitative biology, in that we have experimental results that can be described by a mathematical model," said Manoharan.

Read more at Science Daily

CRISPRed fruit flies mimic monarch butterfly, and could make you vomit

Monarch butterfly
The fruit flies in Noah Whiteman's lab may be hazardous to your health.

Whiteman and his University of California, Berkeley, colleagues have turned perfectly palatable fruit flies -- palatable, at least, to frogs and birds -- into potentially poisonous prey that may cause anything that eats them to puke. In large enough quantities, the flies likely would make a human puke, too, much like the emetic effect of ipecac syrup.

That's because the team genetically engineered the flies, using CRISPR-Cas9 gene editing, to be able to eat milkweed without dying and to sequester its toxins, just as America's most beloved butterfly, the monarch, does to deter predators.

This is the first time anyone has recreated in a multicellular organism a set of evolutionary mutations leading to a totally new adaptation to the environment -- in this case, a new diet and new way of deterring predators.

Like monarch caterpillars, the CRISPRed fruit fly maggots thrive on milkweed, which contains toxins that kill most other animals, humans included. The maggots store the toxins in their bodies and retain them through metamorphosis, after they turn into adult flies, which means the adult "monarch flies" could also make animals upchuck.

The team achieved this feat by making three CRISPR edits in a single gene: modifications identical to the genetic mutations that allow monarch butterflies to dine on milkweed and sequester its poison. These mutations in the monarch have allowed it to eat common poisonous plants other insects could not and are key to the butterfly's thriving presence throughout North and Central America.

Flies with the triple genetic mutation proved to be 1,000 times less sensitive to milkweed toxin than the wild fruit fly, Drosophila melanogaster.

Whiteman and his colleagues will describe their experiment in the Oct. 2 issue of the journal Nature.

Monarch flies

The UC Berkeley researchers created these monarch flies to establish, beyond a shadow of a doubt, which genetic changes in the genome of monarch butterflies were necessary to allow them to eat milkweed with impunity. They found, surprisingly, that only three single-nucleotide substitutions in one gene are sufficient to give fruit flies the same toxin resistance as monarchs.

"All we did was change three sites, and we made these superflies," said Whiteman, an associate professor of integrative biology. "But to me, the most amazing thing is that we were able to test evolutionary hypotheses in a way that has never been possible outside of cell lines. It would have been difficult to discover this without having the ability to create mutations with CRISPR."

Whiteman's team also showed that 20 other insect groups able to eat milkweed and related toxic plants -- including moths, beetles, wasps, flies, aphids, a weevil and a true bug, most of which sport the color orange to warn away predators -- independently evolved mutations in one, two or three of the same amino acid positions to overcome, to varying degrees, the toxic effects of these plant poisons.

In fact, his team reconstructed the one, two or three mutations that led to each of the four butterfly and moth lineages, each mutation conferring some resistance to the toxin. All three mutations were necessary to make the monarch butterfly the king of milkweed.

Resistance to milkweed toxin comes at a cost, however. Monarch flies are not as quick to recover from upsets, such as being shaken -- a test known as "bang" sensitivity.

"This shows there is a cost to mutations, in terms of recovery of the nervous system and probably other things we don't know about," Whiteman said. "But the benefit of being able to escape a predator is so high ... if it's death or toxins, toxins will win, even if there is a cost."

Plant vs. insect


Whiteman is interested in the evolutionary battle between plants and parasites and was intrigued by the evolutionary adaptations that allowed the monarch to beat the milkweed's toxic defense. He also wanted to know whether other insects that are resistant -- though all less resistant than the monarch -- use similar tricks to disable the toxin.

"Since plants and animals first invaded land 400 million years ago, this coevolutionary arms race is thought to have given rise to a lot of the plant and animal diversity that we see, because most animals are insects, and most insects are herbivorous: they eat plants," he said.

Milkweeds and a variety of other plants, including foxglove, the source of digitoxin and digoxin, contain related toxins -- called cardiac glycosides -- that can kill an elephant and any creature with a beating heart. Foxglove's effect on the heart is the reason that an extract of the plant, in the genus Digitalis, has been used for centuries to treat heart conditions, and why digoxin and digitoxin are used today to treat congestive heart failure.

These plants' bitterness alone is enough to deter most animals, but a small minority of insects, including the monarch (Danaus plexippus) and its relative, the queen butterfly (Danaus gilippus), have learned to love milkweed and use it to repel predators.

Whiteman noted that the monarch is a tropical lineage that invaded North America after the last ice age, in part enabled by the three mutations that allowed it to eat a poisonous plant other animals could not, giving it a survival edge and a natural defense against predators.

"The monarch resists the toxin the best of all the insects, and it has the biggest population size of any of them; it's all over the world," he said.

The new paper reveals that the mutations had to occur in the right sequence, or else the flies would never have survived the three separate mutational events.

Thwarting the sodium pump

The poisons in these plants, most of them a type of cardenolide, interfere with the sodium/potassium pump (Na+/K+-ATPase) that most of the body's cells use to move sodium ions out and potassium ions in. The pump creates an ion imbalance that the cell uses to its favor. Nerve cells, for example, transmit signals along their elongated cell bodies, or axons, by opening sodium and potassium gates in a wave that moves down the axon, allowing ions to flow in and out to equilibrate the imbalance. After the wave passes, the sodium pump re-establishes the ionic imbalance.

Digitoxin, from foxglove, and ouabain, the main toxin in milkweed, block the pump and prevent the cell from establishing the sodium/potassium gradient. This throws the ion concentration in the cell out of whack, causing all sorts of problems. In animals with hearts, like birds and humans, heart cells begin to beat so strongly that the heart fails; the result is death by cardiac arrest.

Scientists have known for decades how these toxins interact with the sodium pump: they bind the part of the pump protein that sticks out through the cell membrane, clogging the channel. They've even identified two specific amino acid changes or mutations in the protein pump that monarchs and the other insects evolved to prevent the toxin from binding.

But Whiteman and his colleagues weren't satisfied with this just so explanation: that insects coincidentally developed the same two identical mutations in the sodium pump 14 separate times, end of story. With the advent of CRISPR-Cas9 gene editing in 2012, coinvented by UC Berkeley's Jennifer Doudna, Whiteman and colleagues Anurag Agrawal of Cornell University and Susanne Dobler of the University of Hamburg in Germany applied to the Templeton Foundation for a grant to recreate these mutations in fruit flies and to see if they could make the flies immune to the toxic effects of cardenolides.

Seven years, many failed attempts and one new grant from the National Institutes of Health later, along with the dedicated CRISPR work of GenetiVision of Houston, Texas, they finally achieved their goal. In the process, they discovered a third critical, compensatory mutation in the sodium pump that had to occur before the last and most potent resistance mutation would stick. Without this compensatory mutation, the maggots died.

Their detective work required inserting single, double and triple mutations into the fruit fly's own sodium pump gene, in various orders, to assess which ones were necessary. Insects having only one of the two known amino acid changes in the sodium pump gene were best at resisting the plant poisons, but they also had serious side effects -- nervous system problems -- consistent with the fact that sodium pump mutations in humans are often associated with seizures. However, the third, compensatory mutation somehow reduces the negative effects of the other two mutations.

"One substitution that evolved confers weak resistance, but it is always present and allows for substitutions that are going to confer the most resistance," said postdoctoral fellow Marianna Karageorgi, a geneticist and evolutionary biologist. "This substitution in the insect unlocks the resistance substitutions, reducing the neurological costs of resistance. Because this trait has evolved so many times, we have also shown that this is not random."

The fact that one compensatory mutation is required before insects with the most resistant mutation could survive placed a constraint on how insects could evolve toxin resistance, explaining why all 21 lineages converged on the same solution, Whiteman said. In other situations, such as where the protein involved is not so critical to survival, animals might find different solutions.

"This helps answer the question, 'Why does convergence evolve sometimes, but not other times?'" Whiteman said. "Maybe the constraints vary. That's a simple answer, but if you think about it, these three mutations turned a Drosophila protein into a monarch one, with respect to cardenolide resistance. That's kind of remarkable."

Read more at Science Daily

Oct 3, 2019

Amputees merge with their bionic leg

Scientists have helped three amputees merge with their bionic prosthetic legs as they climb over various obstacles without having to look. The amputees report using and feeling their bionic leg as part of their own body, thanks to sensory feedback from the prosthetic leg that is delivered to nerves in the leg's stump. Djurica Resanovic lost his leg in a motorbike accident several years ago which resulted in amputation above the knee. Thanks to novel neuroprosthetic leg technology, Resanovic was successfully merged with his bionic leg during clinical trials in Belgrade, Serbia.

"After all of these years, I could feel my leg and my foot again, as if it were my own leg," reports Resanovic about the bionic leg prototype. "It was very interesting. You don't need to concentrate to walk, you can just look forward and step. You don't need to look at where your leg is to avoid falling."

Walking with instinct again


Scientists from a European consortium led by Swiss Institutions, ETH Zurich and EPFL spin-off SensArs Neuroprosthetics, with clinical trials in collaboration with institutions in Belgrade, Serbia, successfully characterized and implemented bionic leg technology with three amputees. The results appear in today's issue of Science Translational Medicine.

"We showed that less mental effort is needed to control the bionic leg because the amputee feels as though their prosthetic limb belongs to their own body," explains Stanisa Raspopovic, ETH Zurich professor and co-founder of EPFL spin-off SensArs Neuroprosthetics, who led the study.

He continues, "This is the first prosthesis in the world for above-knee leg amputees equipped with sensory feedback. We show that the feedback is crucial for relieving the mental burden of wearing a prosthetic limb which, in turn, leads to improved performance and ease of use."

Wearing a blindfold and earplugs, Resanovic could feel his/her bionic leg prototype thanks to sensory information that was delivered wirelessly via electrodes surgically placed into the stumps' intact nervous system. These electrodes pierce through the intact tibial nerve instead of wrapping around it. This approach has already proven to be efficient for studies of the bionic hand led by Silvestro Micera, co-author of the publication, EPFL's Bertarelli Foundation Chair in Translational Neuroengineering, professor of Bioelectronics at Scuola Superiore Sant'Anna, and co-founder of SensArs Neuroprosthetics.

Resanovic continues, "I could tell when they touched the [big toe], the heel, or anywhere else on the foot. I could even tell how much the knee was flexed."

Resanovic is one of three leg amputees, all with transfemoral amputation, who participated in a three-month clinical study to test new bionic leg technology which literally takes neuroengineering a step forward, providing a promising new solution for this highly disabling condition that affects more than 4 million people in Europe and in the United-States.

Thanks to detailed sensations from sole of the artificial foot and from the artificial knee, all three patients could maneuver through obstacles without the burden of looking at their artificial limb as they walked. They could stumble over objects yet mitigate falling. Most importantly, brain imaging and psychophysical tests confirmed that the brain is less solicited with the bionic leg, leaving more mental capacity available to successfully complete the various tasks.

These results complement a recent study that demonstrated the clinical benefits of the bionic technology, like reducing phantom limb pain and fatigue.

Bionic leg: from prototype to product


"We develop the sensory feedback technology to augment prosthetic devices," explains Francesco Petrini, CEO and co-founder of SensArs Neuroprosthetics, and who is guiding an effort to bring these technologies to market. "An investigation longer than 3 months, with more subjects, and with in-home assessment, should be executed to provide more robust data to draw clinically significant conclusions about an improvement of the health and quality of life of patients." This project was funded in part by the NCCR Robotics and by the Bertarelli Foundation.

How the bionic leg works: connection between body and machine


The fundamental neuroengineering principle is about merging body and machine. It involves imitating the electrical signals that the nervous system would have normally received from the person's own, real leg. Specifically, the bionic leg prototype is equipped with 7 sensors all along the sole of the foot and 1 encoder at the knee that detects the angle of flexion. These sensors generate information about touch and movement from the prosthesis. Next, the raw signals are engineered via a smart algorithm into biosignals which are delivered into the stump's nervous system, into the tibial nerve via intraneural electrodes, and these signals reach the brain for interpretation.

Read more at Science Daily

Science demonstrates that what doesn't kill you makes you stronger

Scientists at Northwestern University's Kellogg School of Management have established a causal relationship between failure and future success, proving German philosopher Friedrich Nietzsche's adage that "what does not kill me makes me stronger."

The researchers utilized advanced analytics to assess the relationship between professional failure and success for young scientists. They found, in contrast to their initial expectations, that failure early in one's career leads to greater success in the long term for those who try again.

"The attrition rate does increase for those who fail early in their careers," lead author Yang Wang said. "But those who stick it out, on average, perform much better in the long term, suggesting that if it doesn't kill you, it really does make you stronger."

The study, "Early-career setback and future career impact," will be published Oct. 1, in Nature Communications.

The findings provide a counter-narrative to the Matthew Effect, which posits a "rich get richer" theory that success begets more success.

"It turns out that, historically, while we have been relatively successful in pinpointing the benefits of success, we have failed to understand the impact of failure," said Dashun Wang, corresponding author and associate professor of management and organizations at Kellogg.

Methodology and findings


Researchers analyzed records of scientists who, early in their careers, applied for R01 grants from the National Institutes of Health (NIH) between 1990 and 2005. They utilized the NIH's evaluation scores to separate individuals into two groups: (1) the "near-misses" whose scores were just below the threshold that received funding and (2) the "just-made-its" whose scores were just above that threshold.

Researchers then considered how many papers each group published, on average, over the next 10 years and how many of those papers turned out to be hits, as determined by the number of citations those papers received.

Analysis revealed that individuals in the near-miss group received less funding, but published just as many papers, and more hit papers, than individuals in the just-made-it group.

The researchers found that individuals in the near-miss funding group were 6.1% more likely to publish a hit paper over the next 10 years compared to scientists in the just-made-it group.

"The fact that the near-miss group published more hit papers than the just-made-it group is even more surprising when you consider that the just-made-it group received money to further their work, while the near-miss group did not," said Benjamin Jones, study co-author and the Gordon and Llura Gund Family Professor of Entrepreneurship at Kellogg.

Researchers wondered whether the effect could be attributed to a "weed-out" phenomenon -- that the early-career failure caused some scientists in the near-miss group to exit the field, leaving only the most-determined members. Further analysis revealed that while the attrition rate after failure was 10 percent higher for the near-miss group, that alone could not account for the greater success later in their careers.

After testing a number of other possible explanations for the long-term success of the near-miss group, researchers could not find any supporting evidence for any of their hypotheses, suggesting other unobservable factors, such as grit or lessons learned, might be at play.

The research does not contradict the Matthew Effect, but rather suggests a complementary path for those who fail.

"There is value in failure," Dashun Wang said. "We have just begun expanding this research into a broader domain and are seeing promising signals of similar effects in other fields."

Read more at Science Daily

Northern forests have lost crucial cold, snowy conditions

Winter conditions are changing more rapidly than any other season and researchers have found clear signs of a decline in frost days, snow covered days and other indicators of winter that could have lasting impacts on ecosystems, water supplies, the economy, tourism and human health.

As the popular saying goes, "winter is coming," but is it? Researchers at the University of New Hampshire have found clear signs of a decline in frost days, snow covered days and other indicators of winter that could have lasting impacts on ecosystems, water supplies, the economy, tourism and human health.

"Winter conditions are changing more rapidly than any other season and it could have serious implications," said Alexandra Contosta, research assistant professor at UNH's Earth Systems Research Center. "Whether precipitation falls as snow or rain makes a big difference, whether you're talking about a forest stream, a snowshoe hare or even a skier."

In their study, recently published in the journal Ecological Applications, the researchers looked at the last 100 years of weather station data from northern forests across the United States and Canada and the impacts on ecosystems and people. They found a significant decline in "frost days," when minimum temperatures dip below freezing, and "ice days," when maximum temperatures never rise above freezing.

Researchers say that people tend to view cold and snowy weather as burdensome. Yet winter is important for many ecosystems that influence water, wildlife, forests and people. For instance, cold temperatures help prevent the spread of diseases like Lyme disease and West Nile virus through insects like ticks and mosquitoes, as well as help manage insects that are detrimental to trees, like the hemlock wooly adelgid and eastern pine beetle.

A deep and long-lasting snowpack also insulates soils from frigid air temperatures, which prevents roots from freezing, promotes soil nutrient cycling and provides wildlife habitat for burrowing animals. Snow cover is as important to the economy and culture of the northern forest as it is to its ecology, especially for timber harvest, maple sugaring, winter recreation activities like skiing and ice skating, and hunting and fishing essential for indigenous peoples.

"What makes our work unique is that we considered the human effect of climate as well as the ecological or meteorological aspects," said Contosta. "For example, we looked at "mud days," when temperatures are above freezing and no snow cover is present, which can impact not only forest soil nutrients but also loggers who are not able to reach certain areas that can only be harvested with deep snow."

Researchers say much of what is understood about the effects of climate change on ecosystems is based on research conducted during the growing season. Researchers say it's more common to hear about summer climate like drought index or heating degree days. They feel more research needs to be done during the so-called 'dormant' season to fill in the key gaps about how forest ecosystems respond to climate change.

Read more at Science Daily

Ant-plant partnerships may play unexpected role in ant evolution

Partnerships between ant and plant species appear to arise from -- but not drive -- rapid diversification of ants into new species. Katrina Kaur of the University of Toronto, Canada, and colleagues present these findings in PLOS Computational Biology.

Some plants and ants have mutually beneficial, or "mutualistic," interactions: plants provide ants with food or shelter, while ants protect plants against herbivores or disperse their seeds. Previous research has shown that plants with ant partners diversify faster -- showing a bigger net difference between extinction rates and the rise of new plant species -- than do other plants.

Kaur and colleagues wondered if plants affect ant evolution similarly. However, the data they needed was buried in thousands of scientific papers each discussing just one or a few ant species. So, they wrote a computer program to "read" and extract data from over 89,000 paper abstracts, successfully assembling a large database of ant ecological interactions. Then, they mapped the data onto an ant evolutionary tree and modeled how partnering with plants has affected ant diversification.

The analysis produced unexpected results. The researchers hypothesized that ants would first evolve mutualism with plants and then diversify, but their model suggests the opposite: ants that are already rapidly diversifying are more likely to evolve a plant partnership. Once they do, their diversification rates slow.

"To our surprise, the intimate and often beneficial relationships that ants have with plants apparently did not help to generate the over 14,000 ant species on Earth today," Kaur says. "Mutualism may put the brakes on the rise of new species or increase the threat of extinction because an ant's fate becomes linked to its plant partner's."

The researchers plan to use their "text-mining" computer program to assemble an even larger database from thousands of additional papers in order to understand why ant-plant partnerships have different effects on ant versus plant evolution. A similar approach could also reveal insights about other species in mutualistic relationships, such as seed-dispersing birds or human gut microbes.

From Science Daily

Golden ratio observed in human skulls

The Golden Ratio, described by Leonardo da Vinci and Luca Pacioli as the Divine Proportion, is an infinite number often found in nature, art and mathematics. It's a pattern in pinecones, seashells, galaxies and hurricanes.

In a new study investigating whether skull shape follows the Golden Ratio (1.618 ... ), Johns Hopkins researchers compared 100 human skulls to 70 skulls from six other animals, and found that the human skull dimensions followed the Golden Ratio. The skulls of less related species such as dogs, two kinds of monkeys, rabbits, lions and tigers, however, diverged from this ratio.

"The other mammals we surveyed actually have unique ratios that approach the Golden Ratio with increased species sophistication," says Rafael Tamargo, M.D., professor of neurosurgery at the Johns Hopkins University School of Medicine. "We believe that this finding may have important anthropological and evolutionary implications."

The researchers published their findings in the September issue of The Journal of Craniofacial Surgery.

The Golden Ratio can be calculated by taking a line and dividing it into two unequal parts, with the length of the longer part divided by the shorter length being equal to the entire length divided by the longer part. Tamargo's interest in history and anatomy led him in 2010 to publish on finding a human brain and spinal cord in the depiction of God in Michelangelo's Sistine Chapel painting.

Jonathan Pindrik, now a pediatric neurosurgeon at Nationwide Children's Hospital in Ohio, also contributed to the study.

From Science Daily

Oct 2, 2019

Can we peek at Schrodinger's cat without disturbing it?

Quantum physics is difficult and explaining it even more so. Associate Professor Holger F. Hofmann from Hiroshima University and Kartik Patekar from the Indian Institute of Technology Bombay have tried to solve one of the biggest puzzles in quantum physics: how to measure the quantum system without changing it?

Their new paper published this month has found that by reading the information observed from a quantum system away from the system itself researchers can determine its state, depending on the method of analysis. Although the analysis is completely removed from the quantum system, it is possible to restore the initial superposition of possible outcomes by a careful reading of the quantum data.

"Normally we would search for something by looking. But in this case looking changes the object, this is the problem with quantum mechanics. We can use complicated maths to describe it, but how can we be sure that the mathematics describes what is really there? When we measure something there is a trade-off and the other possibilities of what it could be are lost. You cannot find out about anything without an interaction, you pay a price in advance." explains Hofmann.

During Patekar's month-long stay at Hiroshima University when he was an undergraduate student, the two physicists tried to imagine ways of measuring the system without "paying the price" i.e. keeping the system's superposition or meaning that the system can exist in all states. In order to understand their results Hofmann describes their findings using the well-known physics story of Schrödinger's cat:

Schrödinger's cat is in a box and the scientists don't know whether it is dead or alive. A camera is set up looking into the box that takes a photo from a position outside of the box. The photo taken of the cat comes out blurry; we can see there is a cat but not whether it is dead or alive. The flash from the camera has also removed a "quantum tag" marking the superposition of the cat. This photo is now entangled with the fate of the cat i.e. we can decide what happened to the cat by processing this photo in a certain way.

The photo could then be taken away from the box and processed on a computer or in a darkroom. Depending on what method is used to process the photo, we can find out either if the cat is alive or dead, or what the flash did to the cat, restoring the quantum tag. The choice of the reader determines what we know about the cat. We can find out if it's dead/alive or restore the quantum tag that was removed when the picture was taken, but not both.

This is only a step forward in our understanding of quantum mechanics. Today its full application remains confined to expert-level systems like quantum computers, although some of its aspects can also be used in precise measurements, and for secure communication using quantum cryptography.

Read more at Science Daily

African evidence support Younger Dryas Impact Hypothesis

A team of scientists from South Africa has discovered evidence partially supporting a hypothesis that Earth was struck by a meteorite or asteroid 12 800 years ago, leading to global consequences including climate change, and contributing to the extinction of many species of large animals at the time of an episode called the Younger Dryas.

The team, led by Professor Francis Thackeray of the Evolutionary Studies Institute at the University of the Witwatersrand in Johannesburg, South Africa, discovered evidence of a remarkable "platinum spike" at a site called Wonderkrater in the Limpopo Province, north of Pretoria in South Africa. Working with researcher Philip Pieterse from the University of Johannesburg and Professor Louis Scott of the University of the Free State, Thackeray discovered this evidence from a core drilled in a peat deposit, notably in a sample about 12 800 years old. This research was published in Palaeontologia Africana.

Noting that meteorites are rich in platinum, Thackeray said "Our finding at least partially supports the highly controversial Younger Dryas Impact Hypothesis (YDIH). We seriously need to explore the view that an asteroid impact somewhere on earth may have caused climate change on a global scale, and contributed to some extent to the process of extinctions of large animals at the end of the Pleistocene, after the last ice age."

Many mammals became extinct in North America, South America and Europe at the time of the Younger Dryas. In South Africa a few extraordinary large animal species became extinct, not necessarily at exactly 12 800 years ago, but close to that period. These megafauna include a giant African buffalo, a large zebra, and a very big wildebeest.

Human populations may also have been indirectly affected at the time in question. In North America there is a dramatic termination of the stone tool technology of Clovis people. Remarkably, archaeologists in South Africa have detected an almost simultaneous termination of the Robberg stone artefact industry associated with people in some parts of the country, including the area around Boomplaas near the Cango Caves in the southern Cape, close to the town of Oudshoorn.

"Without necessarily arguing for a single causal factor on a global scale, we cautiously hint at the possibility that these technological changes, in North America and on the African subcontinent at about the same time, might have been associated indirectly with an asteroid impact with major global consequences," says Thackeray. "We cannot be certain, but a cosmic impact could have affected humans as a result of local changes in environment and the availability of food resources, associated with sudden climate change."

At Wonderkrater, the team has evidence from pollen to show that about 12 800 years ago there was temporary cooling, associated with the "Younger Dryas" drop in temperature that is well documented in the northern hemisphere, and now also in South Africa. According to some scientists, this cooling in widespread areas could at least potentially have been associated with the global dispersal of platinum-rich atmospheric dust.

A large crater 31 kilometres in diameter has been discovered in northern Greenland beneath the Hiawatha Glacier. "There is some evidence to support the view that it might possibly have been the very place where a large meteorite struck the planet earth 12 800 years ago," says Thackeray. "If this was indeed the case, there must have been global consequences."

Thackeray's team believes their discovery of a platinum spike at about 12 800 years ago at Wonderkrater is just part of the strengthening view that an asteroid or cometary impact might have occurred at that time.

This is the first evidence in Africa for a platinum spike preceding climate change. Younger Dryas spikes in platinum have also been found in Greenland, Eurasia, North America, Mexico and recently also at Pilauco in Chile. Wonderkrater is the 30th site in the world for such evidence.

"Our evidence is entirely consistent with the Younger Dryas Impact Hypothesis" says Thackeray.

The discovery in South Africa is expected to be integrated with those made in other parts of the world, recognising that the source of the platinum at Wonderkrater could hypothetically be cosmic dust that was dispersed in the atmosphere after a meteorite impact in Greenland.

The probability of a large asteroid striking Earth in the future may seem to be low, but there are thousands of large rocks distributed primarily between Jupiter and Mars. One in particular, classified as Apophis 99942, is referred to as a "Potentially Hazardous Asteroid." It is 340 meters wide and will come exceptionally close to the Earth in 10 years' time.

"The closest encounter will take place precisely on Friday April 13, 2029," says Thackeray. "The probability of the Apophis 99942 asteroid hitting us then is only one in 100,000, but the probability of an impact may be even higher at some time in the future, as it comes close to Earth every 10 years."

Read more at Science Daily

The violent history of the big galaxy next door

Astronomers have pieced together the cannibalistic past of our neighbouring large galaxy Andromeda, which has now set its sights on the Milky Way as its next main course.

The galactic detective work found that Andromeda has eaten several smaller galaxies, likely within the last few billion years, with left-overs found in large streams of stars.

ANU researcher Dr Dougal Mackey, who co-led the study with Professor Geraint Lewis from the University of Sydney, said the international research team also found very faint traces of more small galaxies that Andromeda gobbled up even earlier, perhaps as far back as 10 billion years when it was first forming.

"The Milky Way is on a collision course with Andromeda in about four billion years. So knowing what kind of a monster our galaxy is up against is useful in finding out the Milky Way's ultimate fate," said Dr Mackey from the ANU Research School of Astronomy and Astrophysics.

"Andromeda has a much bigger and more complex stellar halo than the Milky Way, which indicates that it has cannibalised many more galaxies, possibly larger ones."

The signs of ancient feasting are written in the stars orbiting Andromeda, with the team studying dense groups of stars, known as globular clusters, to reveal the ancient mealtimes.

"By tracing the faint remains of these smaller galaxies with embedded star clusters, we've been able to recreate the way Andromeda drew them in and ultimately enveloped them at the different times," Dr Mackey said.

The discovery presents several new mysteries, with the two bouts of galactic feeding coming from completely different directions.

"This is very weird and suggests that the extragalactic meals are fed from what's known as the 'cosmic web' of matter that threads the universe," said Professor Lewis from the Sydney Institute for Astronomy and University of Sydney School of Physics.

"More surprising is the discovery that the direction of the ancient feeding is the same as the bizarre 'plane of satellites', an unexpected alignment of dwarf galaxies orbiting Andromeda."

Dr Mackey and Professor Lewis were part of a team that previously discovered such planes were fragile and rapidly destroyed by Andromeda's gravity within a few billion years.

"This deepens the mystery as the plane must be young, but it appears to be aligned with ancient feeding of dwarf galaxies. Maybe this is because of the cosmic web, but really, this is only speculation," Professor Lewis said.

"We're going to have to think quite hard to unravel what this is telling us."

Dr Mackey said studying Andromeda also informed understanding about the way our galaxy has grown and evolved over many billions of years.

"One of our main motivations in studying astronomy is to understand our place in the Universe. A way of learning about our galaxy is to study others that are similar to it, and try to understand how these systems formed and evolved.

"Sometimes this can actually be easier than looking at the Milky Way, because we live inside it and that can make certain types of observations quite difficult."

The study, published in Nature, analysed data from the Pan-Andromeda Archaeological Survey, known as PAndAS.

"We are cosmic archaeologists, except we are digging through the fossils of long-dead galaxies rather than human history," said Professor Lewis, who is a leading member of the survey.

Read more at Science Daily

New approach to pain treatment in diseases of the pancreas

One of the worst symptoms associated with inflammation or cancer of the pancreas is severe chronic pain. Pancreatic pain is difficult to treat, because many painkillers prove ineffective in pancreatic patients. In a recent study, a team at the Technical University of Munich (TUM) discovered the cause of this phenomenon for the first time: a particular neuroenzyme in the body is present in the nerves of the organ in high concentrations.

In many cases only potent analgesics such as opiates are able to relieve the suffering of those affected. But these medications have serious side effects, including dependency, fatigue and constipation. For this reason, scientists have long been searching for better pain therapies for pancreatic patients.

Dr. Ihsan Ekin Demir and his team in the Department of Surgery at TUM's university hospital Rechts der Isar wanted to find out why pain treatment is so difficult and often ineffective in diseases of the pancreas.

Pain mediator profile of the pancreas

They examined pancreatic tissue samples from 42 female and male patients with chronic inflammation (chronic pancreatitis) or cancer of the organ (pancreatic carcinoma). The samples were taken from the head region of the organ. In this area, the nerve density is particularly high, and the pancreatic head is therefore often surgically removed for therapeutic reasons. Tissue donations from healthy subjects served as controls in the new study. The scientists determined the levels of the most important neurotransmitters and neuroenzymes present in nerves of the pancreas for communication and signal transmission.

"We've created a pain mediator profile for this region of the pancreas, which plays a key role in the development and perception of pain. This makes it easy to detect pathological changes," explains Ekin Demir, head of the study.

Inhibitors successfully tested in an animal model

It turned out that a specific enzyme was greatly increased in the nerves of the pancreatic tissue patient samples that were examined: neuronal nitric oxide synthetase (nNOS). This enzyme is responsible for the synthesis of the messenger NO, which plays a role in, among other things, the development of pain. In particular, NO leads to neuronal hyperactivation by binding to receptors on the neuronal surface.

When the scientists then added extracts from the patient samples to nerve cell cultures, the quantity of the nNOS enzyme increased in the cultured nerve cells.

In a well-established mouse model for pancreatic diseases, they then used a specific inhibitor that blocks nNOS. This substance is already approved as an experimental drug but cannot yet be used in humans. Demir's team found that mice receiving the drug were much less sensitive to touch in the affected abdominal area than the control animals. This serves as an indicator of pain perception.

Read more at Science Daily

Carbon emissions soar as tourism reaches new heights

A researcher at The University of Texas at San Antonio (UTSA) is examining how the flight routes people take to get to tourist destinations impact the amount of pollution in the air in a newly published study he coauthored in the Annals of Tourism Research.

"This paper provides one of the first efforts to quantify the carbon emissions associated with tourist air travel in the continental United States," explained Neil Debbage, assistant professor of geography and environmental sustainability in UTSA's Department of Political Science and Geography.

The researchers wanted to know whether nonstop routes to tourist destinations can mitigate air travel carbon emissions compared to connecting routes through big airline hubs.

Using International Civil Aviation Organization data, USTA researchers analyzed carbon emissions for direct and connecting routes between the 10 most-populated metropolitan areas in the northeastern United States (New York, Philadelphia, Boston, etc.) and 13 different tourist destinations located in the Sunbelt and Western regions of the United States (Bexar County, Texas; Los Angeles County, California; Miami-Dade County, Florida; etc.).

Some of the key findings:

  • Nearly half of the routes analyzed exceeded an individual's annual mobility carbon budget for all forms of transportation.
  • Direct routes tended to outperform connecting routes regarding carbon emissions.
  • On average the difference between direct and connecting routes was equivalent to operating a refrigerator for an entire year (or roughly 100 carbon dioxide kg/person).
  • The majority of direct routes in the database generated carbon emissions below the 575 carbon dioxide kg/person annual mobility cap.

"One potential tactic to mitigate the carbon footprint associated with tourist air travel is to select nonstop routes whenever possible," replied Debbage, who worked on the paper with Keith G. Debbage, professor of geography at the University of North Carolina at Greensboro.

The researchers said they hope this paper will help policymakers consider making new initiatives that accelerate technological innovations regarding aircraft fuel usage, jet engines and jet fuel. Additionally, they also emphasized the importance of broader structural shifts such as implementing realistic carbon pricing for air travel.

Neil Debbage's research focuses on climate change, natural hazards and resiliency. He utilizes geographic information systems, statistical modeling and numerical weather modeling to better understand the changing climate at various scales.

From Science Daily

Oct 1, 2019

No need to cut down red and processed meat, controversial findings suggest

Meats and vegetables on a grill.
Most people can continue to eat red and processed meat as they do now. A major study led by researchers at McMaster and Dalhousie universities has found cutting back has little impact on health.

A panel of international scientists systematically reviewed the evidence and have recommended that most adults should continue to eat their current levels of red and processed meat.

The researchers performed four systematic reviews focused on randomized controlled trials and observational studies looking at the impact of red meat and processed meat consumption on cardiometabolic and cancer outcomes.

In one review of 12 trials with 54,000 people, the researchers did not find statistically significant or an important association between meat consumption and the risk of heart disease, diabetes or cancer.

In three systematic reviews of cohort studies following millions of people, a very small reduction in risk among those who had three fewer servings of red or processed meat a week, but the association was uncertain.

The authors also did a fifth systematic review looking at people's attitudes and health-related values around eating red and processed meats. They found people eat meat because they see it as healthy, they like the taste and they are reluctant to change their diet.

The five systematic reviews, a recommendation and an editorial on the topic were published in the Annals of Internal Medicine today.

McMaster professor Gordon Guyatt, chair of the guideline committee, said the research group with a panel of 14 members from seven countries used a rigorous systematic review methodology, and GRADE methods which rate the certainty of evidence for each outcome, to move from evidence to dietary recommendations to develop their guidelines.

"There is a worldwide interest in nutrition and the issue of red meat in particular. People need to be able to make decisions about their own diet based on the best information available," he said.

Bradley Johnston, corresponding author on the reviews and guideline, said the research team realizes its work is contrary to many current nutritional guidelines.

"This is not just another study on red and processed meat, but a series of high quality systematic reviews resulting in recommendations we think are far more transparent, robust and reliable," said Johnston, who is a part-time associate professor at McMaster and an associate professor of community health and epidemiology at Dalhousie.

He added: "We focused exclusively on health outcomes, and did not consider animal welfare or environmental concerns when making our recommendations.

"We are however sympathetic to animal welfare and environmental concerns with a number of the guideline panel members having eliminated or reduced their personal red and processed meat intake for these reasons."

The accompanying editorial by authors at the Indiana University School of Medicine said: "This is sure to be controversial, but is based on the most comprehensive review of the evidence to date. Because that review is inclusive, those who seek to dispute it will be hard pressed to find appropriate evidence with which to build an argument."

Read more at Science Daily

Fruit flies live longer with combination drug treatment

Fruit flies in laboratory.
A triple drug combination has been used to extend the lifespan of fruit flies by 48% in a new study led by UCL and the Max Planck Institute for Biology of Ageing.

The three drugs are all already in use as medical treatments: lithium as a mood stabiliser, trametinib as a cancer treatment and rapamycin as an immune system regulator.

The findings, published in Proceedings of the National Academy of Sciences (PNAS), suggest that a combination drug treatment may one day be helpful at preventing age-related diseases in people.

"As life expectancies increase, we are also seeing an increase of age-related diseases so there is an urgent need to find ways to improve health in old age," said the study's co-lead author, Dr Jorge Castillo-Quan, who began the research at the UCL Institute of Healthy Ageing before moving to Joslin Diabetes Center, Harvard Medical School.

"Here, by studying fruit flies which age much more rapidly than people, we have found that a combination drug treatment targeting different cellular processes may be an effective way to slow down the ageing process."

The researchers were building on previous studies finding that lithium, trametinib and rapamycin can each extend lifespan in fruit flies (Drosophila), which is supported by other preliminary evidence in mice, worms, and cells, and observational findings in people.

The three drugs all act on different cellular signalling pathways that together form the nutrient sensing network, which is conserved across evolution from worms and flies all the way to humans. This network adjusts what the body is doing in response to changes in nutrient levels. The three drugs in question act on different proteins of this network to slow the ageing process and delay the onset of age-related death.

For the latest study, the researchers gave fruit flies doses of lithium, trametinib and rapamycin, separately and in combination. Each drug individually extended lifespan by an average of 11%, while pairing two drugs extended lifespan by roughly 30%. When the three drugs were combined, the fruit flies lived 48% longer than flies in a control group that were not given the treatment.

"Previous studies in fruit flies have achieved lifespan extensions of about 5-20%, so we found it was quite remarkable that this drug combination enabled them to live 48% longer," Dr Castillo-Quan said.

The researchers found that in addition to acting on separate signalling pathways within the nutrient sensing network, the drugs also appear to complement each other to reduce side effects. Rapamycin has undesirable effects on fat metabolism, which can be similar to insulin resistance in people, but lithium appeared to cancel out this effect when the two drugs were given together.

The researchers will continue their research to better understand exactly how the drugs work in combination with each other, and hope to progress to experiments in more complex animals, such as mice, to gauge the effects on the entire body before eventually progressing to human trials.

Principal investigator, Professor Linda Partridge (UCL Institute of Health Ageing and Max Planck Institute for Biology of Ageing), said: "There is a growing body of evidence that polypills -- pills that combine low doses of multiple pharmaceutical products -- could be effective as a medication to prevent age-related diseases, given the complex nature of the ageing process. This may be possible by combining the drugs we're investigating with other promising drugs, but there is a long way to go before we will be able to roll out effective treatments."

"My research groups are working to understand the mechanism of the ageing process in order to find ways to help people stay healthy for longer. We are not trying to cheat death, but help people be healthy and disease-free in their final years," she said.

Read more at Science Daily

Brave new world: Simple changes in intensity of weather events 'could be lethal'

Palm trees in heavy weather.
Hurricane Dorian is the latest example of a frightening trend. Extreme weather events are becoming more frequent, more severe and more widespread as a consequence of climate change. New research from Washington University in St. Louis provides important new insights into how different species may fare under this new normal.

Faced with unprecedented change, animals and plants are scrambling to catch up -- with mixed results. A new model developed by Carlos Botero, assistant professor of biology in Arts & Sciences, and Thomas Haaland, formerly a graduate student at the Norwegian University of Science and Technology, helps to predict the types of changes that could drive a given species to extinction.

The study, published Sept. 27 in the journal Ecology and Evolution, challenges the idea that species previously exposed to more variable conditions are more likely to survive extreme events.

"It is difficult to predict how organisms will respond to changes in extreme events because these events tend to be, by definition, quite rare," Botero said. "But we can have a pretty good idea of how any given species may respond to current changes in this aspect of climate -- if we pay attention to its natural history, and have some idea of the climatic regime it has experienced in the past."

Unexpected vulnerabilities

Researchers in the Botero laboratory use a variety of tools from ecology and evolutionary biology to explore how life -- from bacteria to humans -- copes with and adapts to repeated environmental change.

For the new study, Botero worked with his former student Haaland, now a postdoctoral fellow at the University of Zurich in Switzerland, to develop an evolutionary model of how populations respond to rare environmental extremes. (Think: 500-year floods.) These rare events can be tricky for evolution because it is difficult to adapt to hazards that are almost never encountered.

Through computer simulations, Haaland and Botero found that certain traits and experiences emerged as key indicators of vulnerability.

Specifically, they found:

  • Species that breed a single time in their lifetime tend to evolve conservative behaviors or morphologies, as if they were expecting to experience an environmental extreme every time.
  • In contrast, species in which a single individual can reproduce multiple times and in different contexts (say, a bird that nests several times in a season and in different trees), evolution favors behaving as if environmental extremes simply never happen.

The key insight of this new model is that species belonging to the former, "conservative" category can easily adapt to more frequent or widespread extremes but have trouble adjusting when those extremes become more intense. The opposite is true of species in the latter, "care-free" category.

Haaland and Botero also found that factors speeding up trait evolution are generally likely to hinder -- rather than favor -- adaptation to rare selection events. Part of the reason: High mutation rates tend to facilitate the process of adaptation to normal conditions during the long intervals in between environmental extremes.

"Our results challenge the idea that species that have been historically exposed to more variable environments are better suited to cope with climate change," Botero said.

"We see that simple changes in the pattern and intensity of environmental extremes could be lethal even for populations that have experienced similar events in the past. This model simply helps us better understand when and where we may have a problem."

Applicable to many environmental extremes

The simple framework that Haaland and Botero describe can be applied to any kind of environmental extreme including flooding, wildfires, heatwaves, droughts, cold spells, tornadoes and hurricanes -- any and all of which might be considered part of the "new normal" under climate change.

Take extreme heat as an example. The model can be used to predict what will happen to animal or plant species when there are more heat waves, when heatwaves last longer, or when typical heat waves affect larger areas.

"Regions in which heat waves used to be rare and patchy are likely to host primarily species that do not exhibit conspicuous adaptations to extreme heat," Botero said. "Our model indicates that the biggest threats of extinction in these particular locations will therefore be more frequent or widespread heat waves, and that the species of highest concern in these places will be endemics and species with small geographic distribution.

"Conversely, areas in which heat waves were historically common and widespread can be expected to host species that already exhibit adaptations for extreme heat," Botero added. "In this case, our model suggests that the typical inhabitants of these places are likely to be more vulnerable to hotter temperatures than to longer or more widespread heat waves."

Informing conservation actions

The new model gives wildlife managers and conservation organizations insight into the potential vulnerabilities of different species based on relatively simple assessments of their natural histories and historical environments.

For example, a 2018 study by Colin Donihue, visiting postdoctoral fellow at Washington University, found that Anolis lizards in the Caribbean tend to evolve larger toepads and shorter limb lengths in response to hurricanes because these traits help them cling better to branches during strong winds. The new model suggests that while these lizards are unlikely to be affected by more frequent hurricanes, their populations may nevertheless face a significant threat of extinction if future hurricanes become more intense. A possible solution to this problem might be to provide wind refuges across the island to allow parts of the population escape winds of very high intensity, Botero suggested.

Read more at Science Daily

Molecular basis of vision revealed

Closeup of eye
Researchers have solved the three-dimensional structure of a protein complex involved in vertebrate vision at atomic resolution, a finding that has broad implications for our understanding of biological signaling processes and the design of over a third of the drugs on the market today.

The findings illuminate how signals from photons (particles of light) get amplified in the eye. More importantly, the study provides insights into how the largest family of cell membrane proteins -- G-protein-coupled receptors (GPCRs) -- work in humans.

"They're involved in almost all the biological processes in a human body -- how we perceive light, taste, smell, or how the heart rate is regulated or muscles contract -- and they are targets for over 30% of the drugs that are used today," said Yang Gao, co-first author of the paper and a postdoctoral researcher in the lab of Richard Cerione, the Goldwin Smith Professor of Chemistry and Chemical Biology and co-senior author.

There are over 800 GPCRs in humans that signal through about 20 different G proteins. GPCRs are responsible for sensing a wide range of outside signals -- such as hormones, light, and sense of smell and taste -- and inducing corresponding responses inside the cell. In vertebrate vision, the GPCR rhodopsin is capable of detecting the signal from just one photon and through the activation of the G protein transducin and downstream effectors, amplify it 100,000 times.

The researchers used cryo-electron microscopy to obtain atomic-resolution structures of the rhodopsin-transducin complex. The structures not only provide the molecular basis of vertebrate vision, but also reveal a previously unknown mechanism of how GPCRs in general activate G proteins.

"What we've learnt from these structures at an atomic level may be broadly applicable to other GPCR signaling systems," said co-first author Sekar Ramachandran, a senior research associate in Cerione's lab.

By learning more about how different receptors specifically couple with different G proteins, the researchers hope to gain insights into designing drugs that specifically regulate GPCR signaling. A lot of drug side effects occur when therapies are not specific enough and target both harmful and beneficial pathways, Yang said.

Read more at Science Daily

Sep 30, 2019

Insight into competitive advantage of modern humans over Neanderthals

A team of Japanese and Italian researchers, including from Tohoku University, have evidenced mechanically delivered projectile weapons in Europe dating to 45,000-40,000 years -- more than 20,000 years than previously thought. This study, entitled "The earliest evidence for mechanically delivered projectile weapons in Europe" published in Nature Ecology & Evolution, indicated that the spearthrower and bow-and-arrow technologies allowed modern humans to hunt more successfully than Neanderthals -- giving them a competitive advantage. This discovery offered important insight to understand the reasons for the replacement of Neanderthals by modern humans.

Apparently, Neanderthals and modern humans coexisted in Europe for at least 5,000 years. However, little is known about why modern humans could increase their population size after migrating to Europe and successfully occupy new territories, while autochthonous Neanderthals went extinct ~ 40,000 years ago.

The research team included 17 scientists from Italy and Japan, coordinated by the archaeologists Katsuhiro Sano (Center for Northeast Asian Studies, Tohoku University) and Adriana Moroni (Department of Environment, Earth and Physical Sciences, University of Siena), and the paleoanthropologist Stefano Benazzi (Department of Cultural Heritage, University of Bologna).

They studied 146 crescent-shaped backed pieces (also referred to as lunates or segments) retrieved from the Uluzzian culture of Grotta del Cavallo (Southern Italy), the first Upper Paleolithic culture developed by modern humans in Europe. "Similar backed pieces have been observed in East Africa, although there is no archaeological evidence indicating a route from East Africa into Europe. To better understand the differences in the Uluzzian from previous lithic traditions, as well as the significance of the emergence of this new culture in Europe, it was crucial to identify the function of the backed pieces," said Adriana Moroni.

The backed pieces were macroscopically and microscopically analyzed using a Hirox digital microscope and results were compared with use-wear patterns on experimental samples. Through this analysis, diagnostic impact fractures and microscopic impact linear traces were found on numerous backed pieces, demonstrating that they were used as hunting weapons. "The diagnostic impact fractures showed the similar patterns of experimental samples delivered by a spearthrower and a bow, but significantly different from those observed on throwing and thrusting samples," said Katsuhiro Sano. "Modern humans migrating into Europe equipped themselves with mechanically delivered projectile weapons, such as a spearthrower-darts or a bow-and-arrows, which had higher impact energy hunting strategy and offered modern humans a substantive advantage over Neanderthals," concluded Sano.

Furthermore, fourier transform-infrared (FTIR) spectromicroscopy of residues on several pieces demonstrate that the backed pieces were hafted using a complex adhesive, including ochre, plant gum, and beeswax, which stabilized the hafting. "Comparison with FTIR spectroscopy analyses of several red deposit and soil samples recovered from Grotta del Cavallo ruled out organic contaminants from the burial environment and confirmed the presence of ochre as a mixture of silicate and iron oxides," said Chiaramaria Stani (Elettra-Sincrotrone Trieste).

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Preserving old bones with modern technology

A team of University of Colorado Boulder anthropologists is out to change the way that scientists study old bones damage-free.

If that sounds like a macabre goal, consider this: Bits of well-preserved bones are valuable to researchers studying humans who lived thousands to hundreds of thousands of years ago.

These samples sometimes contain collagen, a useful molecule than can reveal a wealth of information about human remains -- from how long ago a person died to what he or she may have eaten.

"Bone collagen is really a treasure within the realm of archaeology," said Christina Ryder, a graduate student in the Department of Anthropology at CU Boulder.

Now, she and her colleagues have come up with a creative way to be thrifty with that treasure.

In research published this week in the journal Scientific Reports, the group describes a new method for screening bone samples to see if they contain collagen. Unlike existing tools that look for that type of tissue, the team's approach won't damage the bones in the process.

For anthropologists, the test could be "a game changer," said study coauthor Matt Sponheimer, a professor of anthropology at CU Boulder.

"These remains have lain intact for thousands of years, so it always hurts a little bit to destroy a sample," he said. "It's doubly tragic if you do it, and it's all in vain. That's what we're trying to prevent."

It's a goal that emerged out of many hours of frustration. Several years ago, one of Sponheimer's colleagues was tasked with extracting collagen from a series of ancient bone samples. Collagen within bones is a bit like a birth certificate; if scientists can find enough of it, they can use collagen to determine the age of a human specimen through radiocarbon dating.

But this material, which helps to hold together human bones and other tissue, also doesn't age well. Many skeletal remains, even those from well-preserved graves, don't contain much of it.

"My student was spending weeks and, ultimately, months of lab time trying to get dietary info from ancient collagen, and it was working incredibly poorly," Sponheimer said. "I thought to myself, 'There has to be a better way.'"

As it turns out, there was. In their latest study, Sponheimer, Ryder and their colleagues discovered that they could calibrate a machine called a near-infrared spectrometer to test bones for the presence of collagen.

The process is surprisingly easy, Ryder said. The instrument, which operates by way of a handheld probe, scans samples of bone and then -- in a matter of seconds -- churns out an estimate of how much collagen is inside.

"I'll tease that the longest part of the process is typing in the file name," Ryder said.

To make sure that their method was accurate, the researchers tested their instrument on more than 50 samples of ground-up bone with known concentrations of collagen. The tests correctly predicted the approximate concentrations of collagen within each of those samples. It worked with 44 pieces of whole bone, too.

Ryder added that the entire spectrometer is about the size of a briefcase, which means that the team can carry it with them into the field.

It's already gone through one high-profile dry run. Last year, Ryder flew to Germany to meet with colleagues at the Max Planck Institute for Evolutionary Anthropology. The researchers wanted to date human remains uncovered from Dolni Vestonice -- a one-of-a-kind archaeological site in the Czech Republic that hosts some of the oldest known examples of representational art in human history.

"The grad student on this project had only six vials of samples from human burials," Ryder said. "That was all she had, and that was all anyone was going to have for the foreseeable future."

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Purple martin migration behavior perplexes researchers

Purple martins will soon migrate south for their usual wintertime retreat, but this time the birds will be wearing what look like little backpacks, as scientists plan to track their roosting sites along the way.

The researchers recently discovered that purple martins are roosting in small forest patches as they migrate from North America to Brazil. The scientists published their findings in the Journal of Field Ornithology.

"This is highly unusual behavior for songbirds, which typically roost in heavily forested areas," said Auriel Fournier, a co-author of the study with University of Manitoba biological sciences professor Kevin Fraser, who led the research. Fournier is the director of the Forbes Biological Station at the Illinois Natural History Survey.

"It's surprising to see them roosting in these forest islands, which are small, isolated clusters of trees typically surrounded by agriculture, water or recently cut forest," Fournier said.

The researchers want to determine whether the birds are responding to a change in the environment or whether their surprising roosting behavior is something purple martins have always done.

"We believe they must be intentionally seeking out the forest islands," Fournier said. "Because these habitats don't occur very frequently on the landscape, the birds' use of them is unlikely to be by chance."

"We are curious if birds are choosing these isolated patches of habitat because they have fewer predators than in larger patches of forest," Fraser said.

About 13% of the world's birds are colonial nesters, and purple martins are the only songbird species that requires a nest site surrounded by the nests of other similar birds, the researchers said.

"During migration, these birds flock in numbers up to the hundreds of thousands," Fournier said. "It's wild because their flocks are sometimes big enough to be detected by radar."

The researchers had to wait for technology to catch up before they could identify precisely where the birds were stopping to rest during migration. A purple martin weighs about 1.6 ounces (45 grams) and flies an estimated 6,200 to 13,700 miles (10,000 to 22,0000 kilometers) a year. Too much additional weight -- even that of a tiny tracker, for example -- could interfere with the bird's trek.

Thanks to advances in technology, the scientists are using GPS tracking devices small enough to be carried by purple martins. The devices use satellites to pinpoint the birds' location with such accuracy that Fraser and Fournier can identify down to a single tree where a tagged purple martin is roosting at night during migration.

"No one has looked at habitats during migration," Fraser said. "But we need to look so that we can start protecting these birds and their habitats across international boundaries."

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Black holes and their host galaxies, growing old together

Some relationships are written in the stars. That's definitely the case for supermassive black holes and their host galaxies, according to a new study from Yale University. The "special relationship" between supermassive black holes (SMBHs) and their hosts -- something astronomers and physicists have observed for quite a while -- can now be understood as a bond that begins early in a galaxy's formation and has a say in how both the galaxy and the SMBH at its center grow over time, the researchers note.

A black hole is a point in space where matter has been compacted so tightly that it creates intense gravity. This gravity is strong enough that even light can't escape its pull. Black holes can be as small as a single atom or as large as billions of miles in diameter. The biggest are called "supermassive" black holes and have masses equal to that of millions -- or even billions -- of suns.

SMBHs are often found at the center of large galaxies, including our own galaxy, the Milky Way. Although SMBHs were theoretically expected to exist, the first observational hints were detected in the 1960s; earlier this year, the Event Horizon Telescope released the first silhouette of a black hole in the galaxy Messier 87. Astrophysicists continue to theorize about the origins of black holes, how they grow and glow, and how they interact with host galaxies in different astronomical environments.

"There has been a lot of uncertainty regarding the SMBH-galaxy connection, in particular whether SMBH growth was more tightly connected to the star formation rate or the mass of the host galaxy," said Yale astrophysicist Priyamvada Natarajan, senior investigator of the new study, which appears in the journal Monthly Notices of the Royal Astronomical Society. "These results represent the most thorough theoretical evidence for the former -- the growth rate of black holes appears to be tightly coupled to the rate at which stars form in the host."

Natarajan has made significant contributions to our understanding of the formation, assembly, and growth of SMBHs, with respect to their environs. Her work speaks to the underlying question of whether these connections are mere correlations or signs of deeper causation.

Natarajan and her team -- first author Angelo Ricarte and Michael Tremmel of Yale and Thomas Quinn of the University of Washington -- used sophisticated sets of simulations to make the discovery. Called Romulus, the cosmological simulation follows the evolution of different regions of the universe from just after the Big Bang until the present day and includes thousands of simulated galaxies that reside in a wide variety of cosmic environments.

The Romulus simulations offer the highest-resolution snapshot of black hole growth, providing a fully emergent and sharper view of how black holes grow within a wide range of host galaxies, from the most massive galaxies located in the center of galaxy clusters -- very dense regions like crowded city centers -- to much more common dwarf galaxies that inhabit the sparser suburbs.

"At a time when the drivers of black hole growth are unclear, these simulations offer a simple picture. They simply grow along with the stars independent of the galaxy's mass, the larger environment, or the cosmic epoch," said Ricarte, a former graduate student of Natarajan's who is now a postdoctoral fellow at Harvard.

One of the more intriguing findings of the study, Ricarte noted, has to do with the way the largest black holes in the universe interact with their host galaxies over time. The researchers found that SMBHs and their hosts grow in tandem, and that the relationship is "self-correcting," independent of the kind of environment they inhabit.

"If the SMBH starts to grow too rapidly and gets too big for its galactic home, physical processes ensure that its growth slows down relative to the galaxy," Tremmel explained. "On the other hand, if the SMBH's mass is too small for its galaxy, the SMBH's growth rate increases relative to the size of the galaxy to compensate."

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