Culture

Babies mimic songs, study finds

COLUMBUS, Ohio -- Researchers -- and parents -- have long known that babies learn to speak by mimicking the words they hear. But a new study shows that babies also might try to imitate the singing they hear in songs.

As part of the study, scientists captured audio of a 15-month-old boy making sounds similar to the beginning of the song "Happy Birthday," hours after he heard the song played on a toy. An analysis of the sounds showed the boy hitting the first six notes of "Happy Birthday" almost spot-on, in G major.

"We know that throughout the first year of life babies become sophisticated music listeners -- they learn a lot about the patterns of pitches and rhythms in music," said Lucia Benetti, a doctoral student at The Ohio State University School of Music and lead author of the study, which was recently published in the Journal of Research in Music Education. "And infants become better at doing this spontaneously. But we don't know much about how exactly this happens."

The study is among the first to measure an infant's attempt to recreate music by following him for an entire day.

"And what we learned is that in this one case at least, the baby is trying to sing along to songs he's hearing," Benetti said.

For the study, Benetti recorded one infant, a 15-month-old boy named James, through one 16-hour period. James wore a small, light recording device throughout the day, which captured every sound he heard and made. Benetti and her adviser, Eugenia Costa-Giomi, a professor of music education at Ohio State, then analyzed that audio data using software designed to measure language -- things like the number of adult words the baby heard and tried to say. Benetti also listened to the recording and transcribed the music he heard and the music he made, searching for patterns or places where the child seemed to mimic what he heard happening around him.

That technology has primarily been used in previous research studies to collect data that shows how babies develop language, not to understand how they might begin to learn about music.

James' parents also logged his primary activities that day -- things like napping and meals.

In the morning, James spent about 10 minutes with a toy that played the melody of "Happy Birthday." Later that evening, the device recorded James making about 10 sounds, lasting about four seconds, that resembled the beginning of "Happy Birthday."

The researchers shared the recordings with people who didn't know James and didn't know what the researchers were studying. Those listeners reported that James was trying to sing "Happy Birthday."

Shortly after James ate lunch, his mom sang the song "Rain Rain" to him twice. (You know how it goes -- "Rain, rain, go away, come again some other day.") Six hours later, James was playing with his father and started singing a version of "Rain Rain." (The research notes that he sang it for seven seconds in the key of A-flat major.)

James' dad immediately picked up on what his son was trying to do, and sang the song back to him. James repeated it.

(James' dad also made up funny lyrics -- "Scrambled eggs, scrambled eggs, makes big muscles in my legs." James didn't repeat those.)

The study shows that it's possible for babies to learn melodies from the music they hear around them, Benetti said. She said future work could examine a larger group of babies, with more data, to see whether James' response was typical.

"We could try to do it systematically to really start to understand how this learning occurs," she said. "From this study, we at least know that it happens."

The takeaway for parents? It can't hurt to sing to your kids.

"The social aspect of music is important -- if a baby sees their mother singing, they know she's engaging with that song, that she's enjoying it, and they know it must be important," Benetti said.

"I think that social context is important. It's engaging and it's socially relevant, and for them, that's enough."

Credit: 
Ohio State University

Molecular switch mechanism explains how mutations shorten biological clocks

image: Casein kinase 1 (CK1) regulates a core clock protein called PERIOD. A new study explains how mutations in either CK1 or PERIOD can throw off the timing of biological clocks in animals from fruit flies to humans.

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Illustration by Clarisse Ricci/UCSD

A new study of molecular interactions central to the functioning of biological clocks explains how certain mutations can shorten clock timing, making some people extreme "morning larks" because their internal clocks operate on a 20-hour cycle instead of being synchronized with the 24-hour cycle of day and night.

The study, published February 11 in eLife, shows that the same molecular switch mechanism affected by these mutations is at work in animals ranging from fruit flies to people.

"Many people with sleep phase disorders have changes in their clock proteins," said Carrie Partch, associate professor of chemistry and biochemistry at UC Santa Cruz and a corresponding author of the paper. "Generally, mutations that make the clock run shorter have a morning lark effect, and those that make the clock run longer have a pronounced night owl effect."

In the new study, researchers focused on mutations in an enzyme called casein kinase 1 (CK1), which regulates a core clock protein called PERIOD (or PER). Clock-altering mutations in CK1 had been known for years, but it was unclear how they changed the timing of the clock.

CK1 and other kinase enzymes carry out a reaction called phosphorylation, adding a phosphate to another protein. It turns out that CK1 can phosphorylate either of two sites on the PER protein. Modifying one site stabilizes PER, while the other modification triggers its degradation. Partch and her colleagues showed how mutations in either CK1 or PER itself can alter the balance, favoring degradation over stabilization.

PER proteins are part of a complex feedback loop in which changes in their abundance set the timing of circadian rhythms, so mutations that increase the rate of PER degradation throw off the clock.

"What we discovered is this neat molecular switch that controls the abundance of the PER proteins. When it's working right, it generates a beautiful 24-hour oscillation," Partch said.

Partch's lab performed structural and biochemical analyses of the CK1 and PER proteins that suggested how the switch works. To confirm that the interactions observed in the test tube matched the behavior of the proteins in living cells, they worked with researchers at the Duke-NUS Medical School in Singapore. Other collaborators at UC San Diego performed simulations of the molecular dynamics of the switch showing how the CK1 protein switches between two conformations, and how mutations cause it favor one conformation over another.

The switch involves a section of the CK1 protein called the activation loop. One conformation of this loop favors binding of CK1 to the "degron" region of PER, where phosphorylation leads to the protein's degradation. The clock-changing mutations in CK1 cause it to favor this degron-binding conformation.

The other conformation favors binding to a site on the PER protein known as the FASP region, because mutations in this region lead to an inherited sleep disorder called Familial Advanced Sleep Phase Syndrome. The stabilization of PER can be disrupted by either the FASP mutations, which interfere with the binding of CK1 to this region, or by the mutations in CK1 that favor the alternate conformation of the activation loop.

The new findings also suggest why binding of CK1 to the FASP region stabilizes PER. With phosphorylation of the FASP region, that region then acts to bind and inhibit CK1, preventing it from adopting the other conformation and phosphorylating the degron region.

"It binds and locks the kinase down, so it's like a pause button that prevents the PERIOD protein from being degraded too soon," Partch said. "This stabilizing region builds a delay into the clock to make it align with Earth's 24-hour day."

Partch noted that it is important to understand how these clock proteins regulate our circadian rhythms, because those rhythms affect not only the sleep cycle but almost every aspect of our physiology. Understanding these molecular mechanisms may enable scientists to develop therapies for intervening in the clock to alleviate disruptions, whether they are caused by inherited conditions or by shift work or jet lag.

"There might be ways to mitigate some of those effects," she said.

CK1 is also interesting because it seems to be the most ancient component of biological clocks. The whole feedback loop involving CK1, PERIOD, and other core clock proteins is found in all animals from insects to humans. CK1, however, is also found in every other organism with eukaryotic (nonbacterial) cells, including single-celled green algae in which it has been implicated in circadian rhythms.

"Our results provide a mechanistic foundation to understand the essentially universal role of CK1 as a regulator of eukaryotic circadian clocks," Partch said.

Credit: 
University of California - Santa Cruz

Smelling your lover's shirt could improve your sleep

image: Marlise Hofer, the study's lead author and a graduate student in the UBC department of psychology

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UBC Psychology

The scent of a romantic partner can improve sleep, suggests new psychology research from the University of British Columbia.

The researchers found that study participants who were exposed to their partner's scent overnight experienced better sleep quality, even though their partner was not physically present.

"Our findings provide new evidence that merely sleeping with a partner's scent improves sleep efficiency. Our participants had an average sleep efficiency improvement of more than two per cent," said Marlise Hofer, the study's lead author and a graduate student in the UBC department of psychology. "We saw an effect similar in size to what has been reported from taking oral melatonin supplements - often used as a sleep aid."

For the study, the researchers analyzed sleep data from 155 participants who were given two identical-looking t-shirts to use as pillowcases - one had been previously worn by their romantic partner, and the other had either been previously worn by a stranger or was clean.

To capture body odour on the t-shirts, the participants' partners were given a clean t-shirt to wear for 24 hours, and were asked to refrain from using deodorant and scented body products, smoking, exercising and eating certain foods that could affect their body odour. The t-shirts were then frozen to preserve their scent.

Each participant was then given two shirts to place over their pillows, without being told which one was which. They spent two consecutive nights sleeping with each t-shirt. Each morning, they completed a survey about how well-rested they felt. Their sleep quality was also objectively measured using an actigraphy sleep watch that monitored their movements throughout the night. At the end of the study, participants guessed if the shirts they had been sleeping with had previously been worn by their partner.

Participants reported feeling more well-rested on the nights when they believed they were sleeping with their partner's scent. Moreover, regardless of their beliefs about scent exposure, data from the sleep watches indicated that objective sleep improved when participants were actually exposed to their partner's scent.

"One of the most surprising findings is how a romantic partner's scent can improve sleep quality even outside of our conscious awareness," said Frances Chen, the study's senior author and associate professor in the UBC department of psychology. "The sleep watch data showed that participants experienced less tossing and turning when exposed to their partners' scent, even if they weren't aware of whose scent they were smelling."

The researchers say the physical presence of a long-term romantic partner is associated with positive health outcomes such as a sense of safety, calm and relaxation, which in turn leads to better sleep. By signalling recent physical proximity, the mere scent of a partner may have similar benefits.

Hofer says the research could pave the way for future work examining the efficacy of simple and effective methods of improving sleep, such as bringing a partner's shirt the next time you travel alone.

The researchers are currently recruiting participants for a pilot study to investigate whether the scent of parents can improve their infant's sleep quality.

Credit: 
University of British Columbia

Protecting pipelines during land movements

video: An advanced three-dimensional computer model to assess the mechanical performance of a pipeline protected by proposed polymer blocks under a strike-slip (horizontal) fault rupture.

Image: 
Dr Behzad Fatahi

Researchers at the University of Technology Sydney (UTS) have developed a cost-effective and practical method to protect pipelines and keep them operating during significant fault rupture incidents and large ground movements.

Australia's pipeline length of 50,000 km has a critical role in transporting water, gas and oil products, and transferring sewage to treatment plants.

UTS Associate Professor Behzad Fatahi (Head of Geotechnical and Transportation Discipline) supported by Habib Rasouli (PhD Candidate) at the School of Civil and Environmental Engineering developed an advanced three-dimensional computer model to assess the mechanical performance of a pipeline protected by proposed polymer blocks under a strike-slip (horizontal) fault rupture.

While Australia is a relatively stable continental region with low to moderate magnitude earthquakes expected, there are numerous active fault lines such as the Darling fault, extending over 1000 km in the west where most oil products - including 71% of crude oil and condensate - are produced.

"Polymeric geofoam blocks as an inexpensive and light material can offer a safer and cost-effective solution to the challenges faced by Australia engineers passing pipelines through fault lines, increasing Australian competitiveness in international market as well as safety and reliability," said Dr Fatahi.

His findings prove pipes protected with geofoam blocks have a superior performance and remain operational under different strike-slip fault rupture scenarios, while the conventional buried pipelines suffer catastrophic damage. This proposed solution can save lives and reduce the potential environmental disaster due to content leakage.

"We can see how conventional pipelines buried in soil could be severely damaged under a strike-slip fault rupture due to excessive longitudinal compressive and tensile strains in the pipeline, or how the pipe section could be flattened due to bending of the pipeline," he said.

The unacceptable performance of buried water mains, sewage network, and oil and gas pipelines could all lead to environmental disasters due to content leakage.

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University of Technology Sydney

Timing of brain cell death uncovers a new target for Alzheimer's treatment

image: Amyloid hypothesis assumes that extracellular beta-amyloid (Aβ) aggregation is the top of the pathological cascade of Alzheimer's disease, and therefore nothing should occur before extracellular Aβ aggregation. According to the theory, neuronal cell death is the result of this extracellular Aβ aggregation. However, results in this study indicate that intracellular Aβ accumulation induces YAP-dependent necrosis of neurons before formation of extracellular Aβ plaque. Therefore, extracellular Aβ aggregation is not the cause but the result of neuronal death in Alzheimer's disease. Meanwhile, the data do not exclude that extracellular Aβ aggregation is also toxic secondarily.

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Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, TMDU

Researchers led by Tokyo Medical and Dental University find that neuronal necrosis occurs much earlier in Alzheimer's disease progression than originally thought, and uncover a novel target for future treatment strategies

Tokyo, Japan - Alzheimer's remains the leading cause of dementia in Western societies, with some estimates suggesting that as many as 24 million people worldwide are living with the disease. Alzheimer's is characterized by a progressive decline in cognitive ability that eventually affects even basic functions such as walking and swallowing. The exact cause of Alzheimer's is unknown, but pathological changes in the brain, including neuron loss and an accumulation of protein aggregates called beta-amyloid plaques, are a diagnostic hallmark of Alzheimer's disease.

Mild cognitive impairment (MCI) describes the slight but measurable changes in cognitive function that are often a precursor to Alzheimer's disease. However, despite the importance of MCI, very little is known about the changes that occur in the brain during the progression from MCI to Alzheimer's.

In a recent study published in Nature Communications, researchers led by Tokyo Medical and Dental University have now discovered that preventing pathological changes in the brain at the MCI stage could eliminate Alzheimer's disease altogether.

"Neuronal death, is obviously very important in the development of Alzheimer's, but is notoriously difficult to detect in real time because dying cells cannot be stained using chemical or immunohistological methods," says lead author of the study Hikari Tanaka. "Because of this, we used a new biomarker called pSer46-MARCKS to detect degenerative neurites surrounding dying neurons, allowing us to quantify levels of necrosis, a prototype of neuronal death, at different stages of disease."

Surprisingly, the researchers found that neuronal death occurred much earlier than originally thought, with higher levels of necrosis seen in patients with MCI than in patients with full-blown Alzheimer's disease.

The researchers also observed a significant decrease in the levels of a protein known as YAP in Alzheimer's disease model mice and human patients with MCI. YAP positively affects the activity of a second protein called TEAD, a deficiency of which leads to neuronal necrosis. Microscopic examination revealed that the missing YAP was sequestered within beta-amyloid plaques, which have also been linked to neuronal toxicity.

By directly injecting a gene therapy vector expressing YAP analog into the cerebral spinal fluid of mice that were genetically engineered to provide a model of Alzheimer's, the researchers were able to prevent early-stage neuron loss, restore cognitive function, and prevent the development of beta-amyloid plaques.

"Confirming that neuronal necrosis was dependent on YAP was really the pivotal moment for us, but observing the almost transformative effects of YAP supplementation was hugely exciting," says senior author of the study Hitoshi Okazawa. "By showing that neuronal necrosis is YAP-dependent and begins prior to the onset of most symptoms, we predict that novel Alzheimer's disease therapies will be developed to prevent the initiation of Alzheimer's disease."

"Another important issue is that the necrosis of neurons accumulating intracellular beta-amyloid occurs before formation of beta-amyloid plaques," continues Professor Okazawa. "Residual beta-amyloid after neuronal necrosis seems to be the seed for beta-amyloid plaques outside of neurons. This discovery might change the amyloid hypothesis considering that extracellular beta-amyloid plaque is the top of pathological cascade of Alzheimer's disease."

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Tokyo Medical and Dental University

Can beauty be-er ignored?

video: Edge Hill University's Psychology Department has researched the science behind the 'beer goggles' effect, where alcohol consumption can influence whether we find others attractive. We spoke to Dr Rebecca Monk and Professor Derek Heim about their study, including what the 'beer goggles' phenomena means for us.

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Edge Hill University

Dr Rebecca Monk and Professor Derek Heim carried out a computer-based study in bars and pubs local to the University's Ormskirk campus, by asking participants to respond to stimuli while ignoring photos of attractive and unattractive faces.

The findings of the study - published this week in Psychology of Addictive Behaviors - showed that while sober participants were distracted more by attractive faces, the attention of those who were intoxicated was diverted equally by both attractive and unattractive faces.

"Previous research into the beer goggles phenomena yielded inconsistent findings and has been largely limited to asking people directly about how attractive they find others" said Dr Monk, the lead author of the study. "By using an indirect measure of attention, our research was able to overcome some of these limitations.

"We know that attractive faces can pull attention away from the task at hand, but our research suggests that alcohol has the capacity to lessen this effect; to level the playing field."

More than 120 participants - both sober and intoxicated - were asked to indicate on a laptop whether the letter 'T' was the correct way around or inverted, while being told to ignore the series of faces that were shown on the screen at the same time.

Professor Derek Heim added: "Most people have heard of the 'beer goggles' effect, and our research adds to the body of evidence showing that there is some truth to this anecdotal wisdom.

"It's remarkable that in our study participants were only mildly intoxicated, suggesting that it doesn't take much alcohol at all for people to 'put on their beer goggles'."

Credit: 
Edge Hill University

Per-Person Health Care Spending Grew 18% from 2014 to 2018, Driven Mostly by Prices

WASHINGTON D.C. -- Average employer-sponsored insurance (ESI) spending rose to $5,892 per person in 2018, according to the Health Care Cost Institute's annual Health Care Cost and Utilization Report, which analyzes 2.5 billion medical claims to inform the public about trends affecting approximately 160 million U.S. individuals with employer-sponsored insurance. This spending growth outpaced 2017's growth due to continued price growth combined with an uptick in utilization.

"Prices, spending, and out-of-pocket costs continue to rise for the 160 million Americans with employer-sponsored health insurance," said Niall Brennan, president and CEO of HCCI. "Higher prices for medical services continue to drive most spending increases, but in 2018 we also saw an uptick in utilization for the first time in several years. If these price and utilization trends continue, we expect spending growth to stay on an upward trajectory in the coming years."

Despite recent increases in utilization, rising prices were the primary driver of spending growth over the 5-year study period. After adjusting for inflation, spending rose by $610 per person between 2014 and 2018. "Higher prices for medical services were responsible for about three-quarters of overall spending increases between 2014 and 2018, after inflation," said Jean Fuglesten Biniek, report co- author and senior researcher at HCCI.

While utilization changes accounted for a smaller share of spending growth after inflation, about one- fifth, most of the increase in use occurred over just one year. The increase in utilization in 2018 had a greater effect on costs than a similar increase would have had earlier in the period because of price growth between 2014 and 2017.

The report examines four groups of health care services and dozens of sub-categories. Of the four major categories, outpatient visits and procedures saw the highest 2018 spending increase (5.5%).

Other notable trends include:

Inpatient services.

Per-person spending on inpatient admissions rose 11.4% between 2014 and 2018.

Within each sub-category of inpatient admissions, average prices grew steadily between 2014 and 2018 while utilization trends varied. However, the 2.0% price increase in 2018 was lower than the near 4% annual increases from 2014 to 2017.

Outpatient services.

Increases in prices and use led to a 16% increase in spending from 2014 to 2018.

Over that period, ER visit spending increased 32% and spending on observation stays
went up 29%.

Professional services.

Spending increased 16% and growth accelerated over the 5-year period, driven by office visits and administered drugs.

Psychiatry also saw strikingly high spending growth of 43% from 2014 to 2018, which was driven mostly by increased use.

Prescription drugs.

Generic drugs accounted for 88% of all prescriptions.

Out-of-pocket payments for prescriptions for generic drugs was less than one-fifth of out-of-pocket payments on brand drugs.

Out-of-pocket spending grew in each year of the 5-year period. "People with job-based insurance saw their out-of-pocket costs rise 14.5%, or $114, between 2014 and 2018," said John Hargraves, senior researcher and co-author of the report. Study authors stressed that the analysis covers out-of-pocket costs paid for services, such as copays, coinsurance, or deductible payments, but does not include other payments related to health care like insurance premiums.

Methodology. Since 2011, HCCI has tracked, independently analyzed, and reported health care spending, utilization, and prices each year in its Health Care Cost and Utilization Report, using de- identified claims data of people up to age 65 with employer-sponsored health insurance. Data come from four of the largest health insurance providers in the U.S. -- Aetna, Humana, Kaiser Permanente and UnitedHealthcare -- representing about 26 percent of the employer-sponsored insured population. For this year's report utilization and price measures for three of the four service categories (the exception being prescription drugs) were adjusted to account for changes in the mix of services provided in each category, and therefore, facilitate comparisons across years. Further, measures of drug spending reflect discounts negotiated from the wholesale price of drugs but do not include manufacturer rebates that are provided through separate transactions. Thus, drug prices reflect the point-of-sale prices.

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Health Care Cost Institute

Cigarette prices have risen following standardised packaging, despite warnings

The cost of smoking in the UK has risen since the advent of 'plain packs' for cigarettes in 2017, countering claims made by the tobacco industry at the time that the public health measure would lead to discount pricing.

Authors of the new study from the University of Bath's Tobacco Control Research Group (TCRG), argue their findings provide important evidence to policymakers in the UK and around the world of the effectiveness of standardised packaging.

The new paper, published in the journal PLOS One (embargoed 2pm ET / 7pm GMT, Thursday 13 February 2020), highlights the impact of standardised packaging, comparing prices pre- and post-implementation from 2015-18.

During consultation on the introduction of plain packaging for cigarettes in the UK, major tobacco companies claimed smokers would refuse to pay high prices for premium cigarettes in plain packs so the policy would lead to falling prices, which in turn would increase smoking rates.

By analysing tobacco sales data, the researchers from Bath found the reverse: prices were higher one year after standardised packaging legislation was fully adopted, when compared to prices in 2015 when branding was still permitted (by 20p per pack of 20; 60p per RYO 30g pouch).

Principal Investigator and Director of the Tobacco Control Research Group, Professor Anna Gilmore explains: "Like many tobacco industry predictions, their claims did not withstand scrutiny. In fact, we found that prices in most market segments rose faster after the policy than before."

Through their latest analysis, the researchers argue this was achieved partly through the introduction of new requirements under a minimum excise tax (MET). Introduced to coincide with the introduction of plain packs, the MET's objective was to make it harder for the tobacco industry to keep factory made cigarettes cheap.

Cheap tobacco makes it easier for young people to start smoking and harder for smokers to stop. The TCRG's previous work had shown that tobacco companies were gaming the tobacco tax system by over-shifting taxes on their premium products (to maximise profits) and using this to offset minimal revenue on their cheapest products where they absorbed the tax increases to keep these products as cheap as possible.

The MET aims to stops tobacco companies from doing this by forcing them to pay at least £5.88 (currently) to the government every time a pack of 20 cigarettes is sold - it works like a minimum price, but one tobacco companies have to pay in tax.

As the new MET duty was introduced in 2017, prices of the cheapest cigarette brands rose towards the prices of other brands and tax increases were passed on more consistently and quickly to smokers.

Professor Gilmore added: "In short, the MET addressed the industry's cheapest cigarette pricing and reduced its ability to manipulate prices. There is an important message to policymakers around the world here: standardised packaging when introduced within a setting of tax increases, does not appear to result in long term price falls."

Kruti Shrotri, Cancer Research UK's tobacco control manager, said: "Smoking is the biggest cause of health inequalities and raising taxes on tobacco is one of the most effective ways to reduce smoking. "The government should use the next budget to increase taxes above inflation for the sake of public health, and make sure that Stop Smoking Services are properly funded so that people who smoke can get support to quit."

The authors hope these findings can be used in jurisdictions around the world when debating the effectiveness of standardised packaging and to counter tobacco industry claims.

While standardised packs has increased the average price of a pack of RYO tobacco, due to the introduction of a 30g minimum pack size, they suggest more needs to be done. Separate studies from the team, published in recent years suggest HM Treasury officials need to re-evaluate taxation on RYO. Their results from 2018 suggested prices for the most popular brand of RYO should almost double.

Economist and tax expert within the research team at the University of Bath, Dr Rob Branston explained: "Higher taxes need to be levied on Roll Your Own tobacco so that it is on a par with factory made cigarettes when it comes to price. Currently there is a price gap which is encouraging RYO purchasing by smokers - in particular poorer ones - and this measure could help them quit this deadly product."

Credit: 
University of Bath

Transparent human organs allow 3D maps at the cellular level

image: Condensed light travelling end-to-end in a transparent human brain made visible with SHANEL.

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©Helmholtz Zentrum München / Ertürk lab

For the first time, researchers managed to make intact human organs transparent. Using microscopic imaging they could revealed underlying complex structures of the see-through organs at the cellular level. Resulting organ maps can serve as templates for 3D-bioprinting technologies. In the future, this could lead to the creation of on demand artificial organs for many patients in need. The findings published in Cell joined forces from Helmholtz Zentrum München, Ludwig Maximilians University Munich (LMU), and Technical University of Munich (TUM).

In biomedical research, seeing is believing. Deciphering the structural complexity of human organs has always been a major challenge due to the lack of technologies to image them at the cellular level. Recent developments in tissue clearing allowed researchers to obtain first cellular views of intact transparent mouse organs in 3D. These methods, however, were not applicable to human organs.

"We had to change our approach completely"

Human organs are particularly stiff due to accumulation of insoluble molecules including collagen in tissues that have grown for years or even decades. Thus, traditional detergents that are used for making mouse organs transparent do not work on human organs, particularly adult ones. "We had to change our approach completely and start from scratch to find new chemicals which can make human organs transparent," says Shan Zhao, PhD student at Helmholtz Zentrum München and first author of the study. After exhausting trials, the team discovered that a detergent called CHAPS could make small holes throughout the entire stiff human organs. CHAPS allows additional solutions to travel deep into centimeters-thick human organs and convert them into a transparent structure.

After making the human organs transparent, which were obtained post mortem from Prof. Ingo Bechmann's lab at the University of Leipzig, the team had to tackle additional challenges for both organ imaging and the analysis of the large amount of resulting data. First, they developed a new laser-scanning microscope with a large sample holding capacity called "Ultramicroscope Blaze" in collaboration with Miltenyi Biotec. This microscope enabled imaging of human organs as large as the kidney. Next, together with Prof. Bjoern Menze from TUM, the team developed deep learning algorithms to be able to analyze hundreds of millions of cells in 3D.

The researchers named this new technology SHANEL (Small-micelle-mediated Human orgAN Efficient clearing and Labeling). "SHANEL can develop into a key technology for mapping intact human organs in the near future. This would dramatically accelerate our understanding of organs such as the brain, their development and function in health and disease," explains Dr. Ali Ertürk, Director of the Institute for Tissue Engineering and Regenerative Medicine at Helmholtz Zentrum München and also Principal Investigator at the Institute for Stroke and Dementia Research at the hospital of LMU.

Final goal: 3D-bioprinting of artificial organs

Cellular maps of human organs could be used to engineer large scale human tissues and organs with emerging 3D-bioprinting technologies. Towards this goal, Ertürk and his team are currently working on mapping major human organs, starting with the pancreas, heart and kidney.

"There is a huge shortage of organ donors for hundreds of thousands of people," says Ertürk. "The waiting time for patients and the transplantation costs are a real burden. Detailed knowledge about the cellular structure of human organs brings us an important step closer to creating functional organs artificially on demand."

Credit: 
Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH))

Unique organ-specific signature profiles for blood vessel cells

image: Fluorescence microscopy image of the lung with blood vessel endothelial cells shown in green and non-endothelial cells in red.

Image: 
Jalees Rehman

Researchers from the University of Illinois at Chicago have discovered that endothelial cells -- those that create the inner lining of blood vessels -- have unique genetic signatures based on their location in the body.

Their study, which is published in the journal eLife, used a genetic mouse model to compare endothelial cells in their natural organ environment. The researchers first looked at healthy mice and compared how genes were expressed in endothelial cells from heart, lung and brain tissues. Next, they studied the blood vessel endothelial cells of unhealthy mice -- those exposed to a bacterial toxin, which mimicked inflammation in the whole body.

Under both conditions, endothelial cells from various organs expressed distinct genetic signatures.

"One of the most surprising findings of this study is that blood vessel endothelial cells in the brain express genes that were previously thought to be primarily found in neurons -- such as the genes involved in the transport of neurotransmitters and synaptic vesicles," said Dr. Jalees Rehman, UIC professor of medicine, pharmacology and bioengineering at the College of Medicine.

Similar results were found for heart endothelial cells, which expressed the genes known to help heart muscle cells beat and pump blood.

"We have had anecdotal descriptions that blood vessel cells function differently in each organ for some time, but newer genetic tools allowed us to perform a global analysis of thousands of genes in the blood vessels of these vital organs," Rehman said.

Rehman said the results of this study can be used to inform the bioengineering of blood vessels that are specific to different organs and that the findings suggest there are untapped avenues for developing more targeted treatments.

"Our findings provide organ-specific blood vessel 'ZIP codes' for the potential delivery of drugs to specific tissues," Rehman said. "Right now, most treatments for vascular disease target all blood vessels regardless of where they are. Imagine if we could develop more effective treatments to uniquely improve the function of blood vessels in the heart or the brain?"

Rehman said that this research suggests that blood vessels may play previously unrecognized roles in some neurological diseases such as Alzheimer's disease and other forms of dementia because the brain's endothelial cells expressed genes involved in cognitive function.

Credit: 
University of Illinois Chicago

Face-to-face contact with police builds trust in fledgling states

ITHACA, N.Y. - After times of major conflict, such as the civil wars in Liberia from 1980 to 2003, peace often leaves a power vacuum, especially in remote areas not yet reached by a developing government.

"In areas of limited statehood, a country's central authority lacks the ability to implement and enforce rules and decisions," Sabrina Karim, assistant professor of government, wrote in new research published in the American Political Science Review.

The paper, "Relational State Building in Areas of Limited Statehood: Experimental Evidence on the Attitudes of the Police," is based on Karim's research in Liberia. She finds that personal contact between police officers and citizens encourages a positive attitude about the country's central authority because such relationships provide information and facilitate social bonds.

The state earns legitimacy when the public accepts state authority over other sources of authority, including traditional chiefs, criminal groups or external forces such as United Nations peacekeepers.

"As the state expands its enforcement capacity, and as individuals have positive experiences with new state agency personnel, citizens' attitudes toward state authority may change," Karim wrote.

To reach this conclusion, Karim coordinated a study with the Liberian National Police (LNP) to test whether household visits from a pair of police officers - either two male or two female - improved residents' attitudes toward police. Her study also measured whether police officers' gender influenced citizens' acceptance of them.

Building on relationships she's established in Liberia through years of work in the country, Karim collaborated with the LNP to conduct outreach into a rural area, Grand Kru County, as a part of the LNP's community policing expansion.

She prepared four Liberian police officers - teams of two females and two males - to go door to door in randomly selected villages, accompanied by Liberian enumerators. Both teams paid visits of 20-30 minutes each to 375 households; at the end of each visit, officers left a card with the police phone number.

Three weeks later, the 750 households were surveyed about a variety of topics, including perceptions of police. A third set of households, a control group, received no police visits.

The data showed that visits increased citizens' preferences for the police, over alternative sources of security, for a wide range of security issues.

"This could be due to social bonds created with the new state security actor," Karim said. "If citizens did not have personal relationships with a police officer before, the visit put a face to police officers and started a process of trust in the individual police officers who visited them. It led community members to prefer those specific officers to come back and respond if there is a dispute in the community."

There was, however, no added improvement in perceptions of the police among female residents who were visited by female police officers. Karim was surprised at this outcome, but sees it in a positive light.

"Female officers elicit the same response among local men and women as male police officers," she said. "It shows that local men and women are not put off by female police officers."

Based on this study, Karim suggests that building relationships may help a new government earn legitimacy in the eyes of citizens and could help prevent violence in the future.

"The most important kinds of reforms are ones that enable trust-building in the formation of real positive relationships between different groups of people," Karim said, "even more so in a post-conflict country because there's a deficit of trust overall."

Credit: 
Cornell University

Boom and bust for ancient sea dragons

image: The huge ichthyosaur Temnodontosaurus from the Early Jurassic of Germany. This specimen is about 7 m long, but other ichthyosaurs grew up to 21 m.

Image: 
Ben Moon

Ichthyosaurs were fish-like reptiles that first appeared about 250 million years ago and quickly diversified into highly capable swimmers, filling a broad range of sizes and ecologies in the early Mesozoic oceans. However, this rapid pace didn't last long and an evolutionary bottleneck 200 million years ago, through which only one lineage of ichthyosaurs survived, led to much slower evolution in much of their long history.

Dr Ben Moon, who led the research, published in the journal Communications Biology, said: "Ichthyosaurs are a fascinating group of animals to work on because they evolved so many adaptations for living in water very quickly: a fish-like body and tail fin, giving birth to live young rather than laying eggs, and lots of different feeding styles.

"Because of this we expected to see a rapid evolution early after ichthyosaurs first appeared, but we were staggered by just how big this early burst was and how relatively short it was."

There are over 100 known species of ichthyosaur from between 250-90 million years ago in the Mesozoic Era, when the infamous dinosaurs ruled the land and the seas were full of marine reptiles, the top predators that filled comparable roles to dolphins, orcas, and sharks in modern seas.

The study used state-of-the-art computational methods and looked at two types of data, one covering skull size and the other including many features of ichthyosaurs' skeleton. All methods show an 'early burst' of evolution in ichthyosaurs, with high rates and rapid variation soon after the appearance of the group, that quickly diminishes later on.

Co-author Dr Tom Stubbs said: "Ichthyosaurs really dominated early in the Triassic (252-201 million years ago), rapidly evolving in an ocean with few predators soon after the largest known mass extinction in Earth's history. However, the seas quickly became more crowded and competitive, and ichthyosaurs lost their top position in the Jurassic (201-145 million years ago) to other marine reptiles like plesiosaurs and pliosaurs.

"It may well have been the ichthyosaurs' decreasing evolutionary rates which made them less able to adapt quickly, and therefore less diverse and competitive, allowing other marine reptiles to take over as the top predators."

Despite slower evolution and going through a bottleneck at the end of the Triassic period, ichthyosaurs remained a common group but had less variation between them. These are perhaps best known ichthyosaurs, found in several UK locations, including Lyme Regis in Dorset, and first collected by Mary and Joseph Anning.

Dr Ben Moon added: "Even though ichthyosaurs were evolving more slowly in their last 100 million years, they are still known from many species, but with less variety between them.

"It's possible that we might find more ichthyosaurs out there that buck this trend, but it seems that this lack of variety was eventually the cause of their extinction when global conditions became less favourable around 90 million years ago. Ichthyosaurs were simply unable to adapt."

Credit: 
University of Bristol

Huge bacteria-eating viruses found in DNA from gut of pregnant women and Tibetan hot spring

image: Depiction of a huge phage (red, left) and normal phages infecting a bacterial cell.

Image: 
UC Berkeley image courtesy of Jill Banfield lab

Scientists have discovered hundreds of unusually large, bacteria-killing viruses with capabilities normally associated with living organisms.

The huge phages were found by scouring a large database of DNA generated from nearly 30 different environments, ranging from the guts of premature infants and pregnant women to a Tibetan hot spring, a South African bioreactor, hospital rooms, oceans, lakes and deep underground.

The phages -- short for bacteriophage because they "eat" bacteria -- are of a size and complexity considered typical of life, carry numerous genes normally found in bacteria and use these genes against their bacterial hosts.

The findings provide new insight into the constant warfare between phages and bacteria.

The study was done by scientists from the University of Melbourne and the University of California, Berkeley, who identified 351 different huge phages, all with genomes four or more times larger than the average genomes of viruses that prey on bacteria.

Among the discovery was the largest bacteriophage to date: its genome, 735,000 base-pairs long, is nearly 15 times larger than the average phage. This largest known phage genome is much larger than genomes of many bacteria.

"We are exploring Earth's microbiomes and sometimes unexpected things turn up," said Professor Jill Banfield, the senior author of the findings now published in Nature. "These viruses of bacteria are a part of biology, of replicating entities, that we know very little about."

Professor Banfield is now at Berkeley in earth and planetary science and environmental science, policy and management but did a significant portion of her work on the phages when she was in the School of Earth Sciences at the University of Melbourne.

"These huge phages bridge the gap between non-living bacteriophage, on the one hand, and bacteria and Archaea (the diversity of bacteria)," she said. "There definitely seems to be successful strategies of existence that are hybrids between what we think of as traditional viruses and traditional living organisms."

The new findings also have implications for human disease. Viruses in general carry genes between cells, including genes that confer resistance to antibiotics. And since phages occur wherever bacteria and Archaea live, including the human gut microbiome, they can carry damaging genes into the bacteria that colonize humans.

"Some diseases are caused indirectly by phages, because phages move around genes involved in pathogenesis and antibiotic resistance," said Professor Banfield. "And the larger the genome, the larger capacity you have to move around those sorts of genes, and the higher the probability that you will be able to deliver undesirable genes to bacteria in human microbiomes."

Professor Banfield has been studying the diversity of bacteria for more than 15 years.

Credit: 
University of Melbourne

Skyrmions like it hot: Spin structures are controllable even at high temperatures

image: The researchers observed the magnetic skyrmions in an x-ray microscope on a sample of adjustable temperature.

Image: 
ill./©: Kai Litzius

The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated the use of new spin structures for future magnetic storage devices has yet achieved another milestone. The international team is working on structures that could serve as magnetic shift registers, so called racetrack memory devices. This type of storage promises low access times, high information density, and low energy consumption. The new insights published in Nature Electronics shed light on the effects of temperature on the dynamics of skyrmions. According to the researchers' findings, skyrmions move more efficiently at higher temperatures and their trajectories only depend on the speed of the skyrmions. This makes device design significantly easier.

Skyrmions could serve as data bits for racetrack memory devices in the future

The teams at JGU and MIT observed billionfold reproducible motion of skyrmions, a new topologically stabilized spin structure that is a promising candidate to be used as data bits in the racetrack device. The latest experiments were carried out in thin films of magnetic material that stabilize skyrmions at and above room temperature, which is a feature that is required for any application. As it turned out, there currently are limits to the speed of a skyrmion caused by its deformations that will need to be overcome, possibly in antiferromagnetic materials.

"This is a great moment as we have worked for a long time to get this study completed. Now that we know that skyrmions can be moved billionfold and at high temperatures that are typical for the insides of a computer, we can focus on tackling the high-speed regime and get the device from its experimental state to being superior to existing storage technology," said Dr. Kai Litzius, lead author of the article. Litzius conducted this work at Johannes Gutenberg University Mainz, combined with a research stay at MIT. After finishing his PhD, he moved to the United States to work at MIT as a postdoctoral associate.

Cooperation with leading international partners as the cornerstone of successful research

"I am very happy to see the next step taken for using skyrmions as magnetic bits in novel devices. The international collaboration with leading partner universities is crucial to enable such work and such collaborations, and exchanges of people are a cornerstone of our graduate education programs," emphasized Professor Mathias Kläui, corresponding author of the paper. "With funding from the German Academic Exchange Service, the Collaborative Research Center CRC/TRR 173 Spin+X, and the Graduate Programs MAINZ - Materials Science in Mainz and MPGC - Max Planck Graduate Center with Johannes Gutenberg University Mainz, we foster these collaborations and exchanges that can be the stepping stone for the next career step."

Credit: 
Johannes Gutenberg Universitaet Mainz

'Rosetta stone' for urban scaling makes sense of how cities change across time and space

image: Space-shifting reflective sculpture in Chicago, Il.

Image: 
Petr Kratochvil/Public Domain

Cities change as they grow -- not only by adding area or population but also in a variety of other ways, from the length and width of their roads to economic growth to the distribution of elementary schools. Social scientists often clash over the best way to measure change as a city swells. Traditionally, they've taken a cross-sectional approach, which means collecting data on a large number of cities of diverse sizes at the same moment in time. More recently, some researchers have begun studying individual cities over time, in what's called temporal scaling.

"These two dimensions, time and population size, need to be treated separately because they express different phenomena," says Luís Bettencourt, an external professor at the Santa Fe Institute and director of the University of Chicago's Mansueto Institute for Urban Innovation. "We need both of them to make sense of what is happening in a complex system like a city."

New work, led by Bettencourt, maps out the common ground between these two approaches. In a paper published this week in the Journal of the Royal Society Interface, the authors argue that while the two methodologies measure different mixtures of the same phenomena, they can be used together to reveal new insights about a city's behavior.

Each approach can be used to calculate an exponent describing the growth rate of some property. (Cross-sectional analyses suggest, for example, that traffic congestion scales exponentially as the size of the city, with an exponent of 7/6.) Those exponents don't necessarily line up, but they don't have to be at odds.

"Now, we're able to have this way to disentangle the two approaches, and bring these two scaling methods back together," says Vicky Chuqiao Yang, an Omidyar Fellow at the Santa Fe Institute who worked on the paper. "With the formalism we've derived in the paper, we've shown mathematically how these exponents are related between the two approaches."

Scaling behaviors have long been observed and analyzed in physical systems of liquids and gases. Similarly, researchers have long found successful ways to map how properties scale for biological organisms--with the size of animals, for example. "They've compared mice with cows with elephants and found properties that change in a predictable way with size, which spans orders of magnitude," says Yang. But temporal scaling is not obvious in biology, because social systems like cities can grow indefinitely and organisms stop once they reach maturity.

In recent years, as large datasets on urban areas around the world have become available, researchers like Bettencourt and Yang have begun analyzing scaling behaviors that emerge in human systems -- including cities. The field really ignited about a decade ago, she says, when researchers from the Santa Fe Institute first showed that many properties of cities also changed in a predictable way over orders of magnitude in city size.

"There was this mysterious phenomenon that the properties of cities change in systematic ways with its size," says Yang. "That included things like fewer gas stations per capita, and a boost in socioeconomic activity, such as more research and development." Since then, researchers have found that many interesting socioeconomic properties increase disproportionally fast with population, said to be "superlinear." Some others grow disproportionally slowly and are said to be "sublinear."

Such scaling behavior has been found in systems ranging from hunter-gatherer societies to modern companies. The new framework offers a way to better understand and quantify properties with systematic trajectories -- and even understand which ones contribute to the health of human institutions. It could, for example, give researchers a way to analyze how a phenomenon like economic growth changes with time and with population size (but does so along both dimensions in different ways). Bettencourt likens the new work to a Rosetta Stone that allows researchers to translate their findings between the two types of scaling.

Credit: 
Santa Fe Institute