Culture

Getting a better look at living cells

image: Tolou Shokuhfar, associate professor of bioengineering at the University of Illinois at Chicago College of Engineering.

Image: 
UIC

Nanoscale-level imaging of living cells has become a reality in the past few years using transmission electron microscopy and sealed sample holders that keep cells alive in a liquid environment. But do the high-resolution images obtained using these tools truly reflect the structures and functions of cells, or do they show cells damaged by the high-intensity electron beam used in transmission electron microscopy?

"We really have had no way of knowing if what we see in images obtained through liquid cell transmission electron microscopy show the natural state of cells, or if the morphological changes we see are actually the result of radiation damage," said Tolou Shokuhfar, associate professor of bioengineering at the University of Illinois at Chicago College of Engineering.

Shokuhfar and colleagues describe a device that works with most transmission electron microscopes that would significantly reduce the exposure of live samples to the electron beam used in transmission electron microscopy. They report their results in the journal Science Advances.

Transmission electron microscopy produces incredibly detailed images of cells that can show structures as small as one or two nanometers across. But for a long time, samples used in transmission electron microscopy had to be dead or frozen because the sample chamber of a transmission electron microscope is a vacuum.

The new field of liquid cell transmission electron microscopy emerged in recent years enabling scientists to study biological, chemical and materials science samples in their near-native environments. This is achieved by placing the sample in liquid inside a tiny sealed chamber that protects it from the high vacuum environment to allow dynamic imaging.

However, currently-available devices that hold samples only allow for a single chamber to be placed under the microscope at a time. "Because you place just one sample at a time under the microscope, you need to perform your pre-imaging focus and setting adjustment on that one sample," said Trevor Moser, a graduate student at Pacific Northwest National Laboratory in Richland, Washington and a co-author on the paper. "By the time you are ready to take pictures, the sample has already been exposed to significant amounts of radiation, so you just never know if the pictures you get show the unaltered cell, or if what you see on the pictures is because of damage from the electron beam," continued Moser, who has previously worked in Shokuhfar's lab.

The research team solved this problem by developing a device with 25 transparent windows rather than the single window sample holders currently provide. With more windows, the researchers expose samples to less radiation by getting closer to the settings and focus they need using one of the windows and then switching to another window where cells haven't yet been exposed to the radiation from the microscope's electron beam. Researchers still need to focus on samples in the 'fresh' window, but they don't have as many adjustments to make, significantly limiting total exposure to the electron beam before images are taken.

Next, the researchers proved that their device could prevent alteration of samples caused by overexposure to electron radiation. They imaged a bacterium called Cupriavidus metallidurans, a small single-celled organism that produces solid gold nanoparticles from aqueous gold tetrachloride, a potent heavy metal toxin to most organisms.

First, they imaged the bacteria by exposing it to increasing levels of radiation over the course of focusing and adjusting their settings before taking pictures. Then, they imaged a second batch of bacteria using their novel 25-window device. The images they produced showed significant differences.

"The images of cells exposed to higher levels of radiation were clearly different from cells imaged with no previous radiation exposure," said James Evans, a senior scientist at Pacific Northwest National Laboratory and a co-author on the paper. "This proves that damage caused by being in the electron beam too long can cause artifacts that can yield false information. We saw much more pristine, undamaged cells using our multi-chamber device."

Shokuhfar, a corresponding author on the paper, said the new device will also enable higher-fidelity imaging of nanoparticles using transmission electron microscopy. "Nanoparticles are also susceptible to damage from radiation, so this device will let us observe more accurately, how nanoparticles grow and change under different conditions, which has application in areas of new materials, nanoparticle interactions and medicine," she said.

Credit: 
University of Illinois Chicago

Rhythm crucial in drummed speech

image: The Amazonian Bora people mimic the rhythm of their language using drums.

Image: 
GAIAMEDIA/AEXCRAM

The human voice can produce rich and varied acoustic signals to transmit information. Normally, this transmission only has a reach of about 200 metres. The Boras, an indigenous group of about 1,500 members residing in small communities in the Amazonian rainforest of Colombia and Peru, can extend this range by a factor of 100 by emulating Bora phrases in sequences of drumbeats. The Boras do this with manguaré drums pairs of wooden slit drums traditionally carved from single logs (each about two metres) through burning. Each drum can produce two pitches, a pair four in total.

Public announcement

The Boras use manguaré drums in two ways. One is the "musical mode", which is used to perform memorised drum sequences with little or no variation as part of rituals and festivals. The other is the "talking mode", which is used to transmit relatively informal messages and public announcements. "For example, the manguaré is used to ask someone to bring something or to come do something, to announce the outcome of non-alcoholic drinking competitions or the arrival of visitors", says Seifart of the former Department of Linguistics at the Max Planck Institute for Evolutionary Anthropology where the major part of the now published work was done. "In this model, only two pitches are used and each beat corresponds to a syllable of a corresponding phrase of spoken Bora. The announcements contain on average 15 words and 60 drum beats."

Rhythm essential

The Boras use drummed Bora to mimic the tone and rhythm of their spoken language and to elaborate Bora phrases in order to overcome remaining ambiguities. "Rhythm turns out to be crucial for distinguishing words in drummed Bora", says Seifart. "There are four rhythmic units encoded in the length of pauses between beats. These units correspond to vowel-to-vowel intervals with different numbers of consonants and vowel lengths. The two phonological tones represented in drummed speech encode only a few lexical contrasts. Rhythm therefore appears to crucially contribute to the intelligibility of drummed Bora."

This, the researchers argue, provides novel evidence for the role of rhythmic structures composed of vowel-to-vowel intervals in the complex puzzle concerning the redundancy and distinctiveness of acoustic features embedded in speech.

Credit: 
Max Planck Institute for Evolutionary Anthropology

Landmark paper finds light at end of the tunnel for world's wildlife and wild places

image: A new paper finds that trends toward population stabilization, poverty alleviation, and urbanization are rewriting the future of biodiversity conservation in the 21st century, offering new hope for the world's wildlife.

Image: 
Cristian Samper

NEW YORK (April 23, 2018) - A new WCS paper published in the journal BioScience finds that the enormous trends toward population stabilization, poverty alleviation, and urbanization are rewriting the future of biodiversity conservation in the 21st century, offering new hope for the world's wildlife and wild places.

The paper, written by Eric Sanderson, WCS Senior Conservation Ecologist; Joe Walston, WCS Vice President for Field Conservation; and John Robinson, WCS Executive Vice President for Global Conservation, says that for the first time in the Anthropocene, the global demographic and economic trends that have resulted in unprecedented destruction of the environment are now creating the necessary conditions for a possible renaissance of nature.

Most people think that the population of people on Earth will always rise, but these authors point out that the demographic transition is already well underway. The rate of growth in global population has been dropping since the 1960s. They cite new demographic research that suggests the world population in 2100 could be as high as 12 billion or as low as 7 billion, fewer people than are alive today. The difference depends on actions we take today.

Good urbanization is key. Cities lead people to choose to have smaller families, and the increased income urbanites derive from working in town mean that people can choose to conserve nature, not destroy it, through choices about what they buy and how they live.

These considerations lead the authors to suggest that within our generation, or the generation to follow, if society makes the right moves now, there could be possibilities for rewilding unimaginable to previous generations of conservationists.

They call their thinking "From Bottleneck to Breakthrough." Recognition of the massive demographic, economic and urbanization trends suggest that conservation will best succeed if we protect the world's threatened wildlife and wild places through the bottleneck; create safe, attractive, sustainable cities; encourage better consumer choices by costing in the environmental benefits or harms of different resources and pollutants; and by inspiring all people and all institutions of the world to care for, rather than destroy, the natural bases of life on Earth.

Said lead author Eric Sanderson: "A light is appearing at the end of the tunnel, but for that light to be sunshine and not a train, it is critical that the world's nations act now."

Credit: 
Wildlife Conservation Society

Scientists generate an atlas of the human genome using stem cells

image: This photo shows haploid human embryonic stem cells created at the Hebrew University's Azrieli Center for Stem Cells and Genetic Research.

Image: 
Azrieli Center for Stem Cells and Genetic Research, Hebrew University of Jerusalem

Scientists from the Hebrew University of Jerusalem have generated an atlas of the human genome using a state-of-the-art gene editing technology and human embryonic stem cells, illuminating the roles that our genes play in health and disease. The scientists have reported their findings in the journal Nature Cell Biology.

Embryonic stem cells are a unique resource as they can turn into any adult cell in our bodies. Their versatile nature puts them at the center of attention in the fields of regenerative medicine, disease modeling and drug discovery. In parallel to the discovery of human embryonic stem cells, another milestone in biology was completed with the sequencing of the human genome, and the identification of the entire set of genes responsible for our genetic identity. This finding has led to a new challenge of understanding the function of the genes in the human genome. Now, the new study by scientists at the Hebrew University provides a novel tool to map the function of all human genes using human embryonic stem cells.

The researchers analyzed virtually all human genes in the human genome by generating more than 180,000 distinct mutations. To produce such a vast array of mutations, they combined a sophisticated gene-editing technology (CRISPR-Cas9 screening) with a new type of embryonic stem cells that was recently isolated by the same research group. This new type of stem cells harbors only a single copy of the human genome, instead of two copies from the mother and father, making gene editing easier thanks to the need of mutating only one copy for each gene (see: 'Scientists generate a new type of human stem cell that has half a genome,' March 17, 2016, https://new.huji.ac.il/en/article/29863).

The researchers show that a mere 9% of all the genes in the human genome are essential for the growth and survival of human embryonic stem cells, whereas 5% of them actually limit the growth of these cells. They could also analyze the role of genes responsible for all hereditary disorders in early human development and growth. Furthermore, they showed how cancer-causing genes could affect the growth of the human embryo.

"This gene atlas enables a new functional view on how we study the human genome and provides a tool that will change the fashion by which we analyze and treat cancer and genetic disorders," said Prof. Nissim Benvenisty, MD, PhD, Director of the Azrieli Center for Stem Cells and Genetic Research and the Herbert Cohn Chair in Cancer Research at the Hebrew University of Jerusalem, and the senior author of the study.

Another key finding of the study was the identification of a small group of genes that are uniquely essential for the survival of human embryonic stem cells but not to other cell types. These genes are thought to maintain the identity of embryonic stem cells and prevent them from becoming cancerous or turning into adult cell types.

"This study creates a new framework for the understanding of what it means to be an embryonic stem cell at the genetic level," said Dr. Atilgan Yilmaz, PhD, postdoctoral fellow and a lead author on the paper. "The more complete a picture we have of the nature of these cells, the better chances we have for successful therapies in the clinic."

Credit: 
The Hebrew University of Jerusalem

Upswings in older-age cognitive ability may not be universal

A growing body of evidence indicates that rates of dementia may be declining, in part because older adults' cognitive abilities, such as learning and memory functions, are better than those of older adults in the past. But most data have come from almost entirely white cohorts living in high-income countries, calling into question the universality of the trend.

Now, a study of a majority-black cohort, led by a Boston University School of Public Health (BUSPH) researcher, finds no clear upward trend in cognitive abilities among older adults.

Published in a special supplement to the Journal of Gerontology aiming to broaden the understanding of dementia trends in the United States, the study found trends in cognitive performance differed by race and cognitive function. Although the highest scores in cognitive performance rose in each consecutive round of the study, the lowest scores dropped precipitously. Black participants also scored consistently lower than their white counterparts.

"Our findings suggest that the previously observed upswings in cognitive abilities in older age might not be shared by all groups," says lead author Jennifer Weuve, associate professor of epidemiology at BUSPH.

"What we had expected to see was that, for example, a 75-year-old in 2010 would perform better than a 75-year-old in 2005, who would perform better than a 75-year-old in 2000, and so on," she says. "But overall, there were few clear and consistent signals of secular improvement."

The study used data from the Chicago Health and Aging Project (CHAP), which has followed a total of 10,802 individuals 65 years old or older living on the south side of Chicago since 1993. The cohort is 60 percent black and 40 percent white by self-identification, meaning it has the greatest number of black participants--often by an order of magnitude--than any previous comparison of cognitive decline and dementia in black and white older adults.

CHAP participants underwent cognitive assessments in six three-year study cycles from 1993-1996 through 2010-2012. The researchers computed three measures of cognitive performance: episodic memory, perceptual speed, and a "global" measure of cognition that summarized performance on the entire battery of four tests.

The researchers found a modest decline in mean global cognitive scores over the 18-year period. They found a steeper drop in perceptual speed than in episodic memory, with a more pronounced difference in the rate of decline of the two measures among white participants than black participants. The researchers also saw different trends in the top-scoring and bottom-scoring quartiles of participants, with scores for the top quartile rising slightly over the study period and scores for the bottom quartile dropping dramatically.

The disparity between black and white participants' mean scores narrowed over the first five of the three-year cycles, from 1993 to 2009, but widened again between 2009 and 2012, especially in the perceptual speed score. (Read about previous CHAP research on possible causes of the racial disparity in cognitive performance here.)

"Our study is among the few to include non-white participants, and among the few to examine secular trends among the highest- and lowest-performing older adults," Weuve says. "If the goal is to understand the full burden of cognitive aging on society, monitoring cognitive and dementia trends in all segments of the population is fundamental."

Credit: 
Boston University School of Medicine

How your brain learns to expect mud puddles in the park (and other things)

Updated expectations are vital for making decisions

Your midbrain encodes the expectation error and relays it to the frontal lobe to revise

Dopamine neurons are likely involved in encoding identity errors and new expectations in brain

CHICAGO --- When scientist Thorsten Kahnt was a high school student in Nuremberg, Germany, his friend Christian sported chin-length, curly brown hair. Then one day Christian appeared with newly buzzed hair, only half an inch long.

When Kahnt saw his newly shorn friend, his midbrain blinked, "Error! Error!"

At least, that's what Kahnt knows now, based on his new Northwestern Medicine study about how neurons in the midbrain encode errors in our identity expectations and how the orbitofrontal cortex updates them.

"This happens all the time in our lives," said Kahnt, an assistant professor of neurology at Northwestern University Feinberg School of Medicine. "Whenever there's a mismatch between what we expect to experience and what we actually experience, our brain has to register the error and update our expectation. These changing expectations are fundamental for making decisions. Now we know how this happens in the brain."

"It could be as basic as taking your kid to the park and expecting green grass, but instead the ground is a big, muddy puddle," Kahnt said. "Your midbrain responds to the error, and the orbitofrontal cortex updates the information, so you know what to expect tomorrow."

The paper describing the human midbrain's role in identity expectations will be published April 23 in Nature Communications.

Previous research has identified the midbrain's role in learning about preferences. This is the first paper to show its role in encoding identity errors and how those are used to update expectations in the orbitofrontal cortex.

Kahnt believes these identity errors are encoded by dopamine neurons because these neurons also encode errors that relate to our preferences. Presumably, dopamine is released at the neuron's axon terminal in the orbitofrontal cortex where it updates the identity information.

In addition, a recent paper reporting a similar experiment in rodents showed dopamine neurons in the midbrain encode errors in identity expectations.

How the study worked

To create different identities of outcomes, the scientists used odors corresponding to sweet and savory foods. Hungry participants learned associations between visual stimuli and these food odors by observing pairs repeatedly. Unexpectedly to the participant, after some time researchers changed the identity of the expected odor. They presented a different food odor (e.g., pot roast), after participants saw a visual stimulus that was previously paired with a different odor (e.g., caramel).

Functional magnetic resonance imaging (fMRI) data showed that when an unexpected odor was presented, activity in the midbrain increased. Moreover, the study showed that at the time when the visual stimulus was presented, patterns of fMRI activity in the orbitofrontal cortex encoded the identity of the odor that was expected.

Once the association between the stimulus and the odor was changed, these "identity expectations" changed accordingly. Further analyses showed that identity expectations in the orbitofrontal cortex changed proportionally to the size of responses in the midbrain.

Credit: 
Northwestern University

Antibiotic resistance can be caused by small amounts of antibiotics

Antibiotic-resistant bacteria are a global and growing problem in health care. To be able to prevent further development of resistance developing, it is important to understand where and how antibiotic resistance in bacteria arises. New research from Uppsala University shows that low concentrations of antibiotics, too, can cause high antibiotic resistance to develop in bacteria.

In the present study in question, published in Nature Communications, the researchers have investigated how prolonged exposure to low levels of antibiotics contributes to the development of bacterial antibiotic resistance. During a course of antibiotics, a high proportion of the antibiotic dose is excreted in the urine in unchanged, active form, and can then spread into watercourses, lakes and soil in the wastewater. Consequently, these environments may contain low levels of antibiotics. In some parts of the world, large quantities of antibiotics are used in meat production and aquaculture, where small doses of antibiotics are added to the animal feed to make the animals grow faster. This means that the bacteria in their intestines are exposed to low levels of antibiotics over long periods and these bacteria can then, in turn, infect people via food, for example.

In the paper, the researchers show that low concentrations of antibiotics, too, play a major part in the development of resistance. The study showed that, over time, bacteria exposed to low doses of antibiotics developed resistance to antibiotic levels that were more than a thousand times higher than the initial level to which the bacteria were subjected. It was also found that the mutations in the bacterial DNA that cause resistance are of a different type than if they have been exposed to high doses. During the experiment, the bacteria eventually acquired several mutations. Each of these yielded low resistance, but together they brought about very high resistance. In addition, the mutations took place mainly in genes that have not previously been regarded as typical resistance genes, suggesting that the number of genes capable of promoting development of resistance has been greatly underestimated.

"The results are interesting because they show that the very low antibiotic concentrations present in many environments, too, can lead to a high degree of resistance and contribute to the problem of resistance," says Professor Dan I Andersson, who headed the study.

Credit: 
Uppsala University

Why have all Western-owned digital firms failed in China?

A new study from Cass Business School examines the failures of Western Internet Firms (WIFs) in China and why this phenomenon is singularly prevalent in this region.

"Government censorship and control, plus cultural differences between China and the West are often cited as the main reasons for such failures," said Professor Feng Li, the study's author. "But similar conditions existed in other countries such as Indonesia, Thailand and Saudi Arabia, that did not prevent western internet firms such as Google from dominating 90 per cent of the search market in these regions."

What is a Western Internet Firm?

By definition Western Internet Firms (WIFs), also known as digital firms, are organisations that from inception focus on digital services enabled by the Internet and related technologies including mobile.

These firms were born digital, particularly the so-called dot.com and e-Commerce firms, such as search engines, online content providers and retail platforms. Typical examples include Google, eBay and Amazon. It does not include traditional IT firms, such as Microsoft, Intel or IBM, which rely on sales of hardware and software as their main sources of revenue.

Why digital firms fail in China

The reasons for these systematic failures are complex, and existing international business theory could not fully explain why the perceived competitive advantages for western multinational firms failed to translate into sustainable operational success for WIFs in China.

In answer to this, Professor Li took a different approach by using phenomenon-based research looking at a broad spectrum of participants such as senior executives from WIFs and their Chinese competitors, and a large number of business, political, and professional groups with a deep knowledge of China.

1. Perceptions of aggressive competition

Most WIFs entered China to dominate the Chinese market. However, competition is relative. What is considered aggressive by western standards is often seen as mild in China. Due to the sheer number of internet firms and the huge size of the Chinese market, competition is often extremely fierce, and to survive, all Chinese Internet Firms (CIFs) have to compete with a far greater pool of local competitors than any WIFs have ever encountered.

Professor Li said, "This is known as the 'huge crowd strategy' (???? - Ren hai zhan shu), which gives CIFs an implicit advantage. If western internet behemoths such as Amazon and Google succeeded in the US by beating hundreds of competitors, then Alibaba and Baidu would have to beat tens of thousands of competitors in China to get where they are."

2. Failure to follow cultural strategies

CIFs have, explicitly and implicitly, drawn inspirations from ancient Chinese military strategies and tactics to change the nature of competition. Such strategies, taken from texts like the 'The Art of War' to 'The Thirty Six Stratagems', are deeply ingrained in Chinese history and culture and widely used in everyday language, which enables more effective strategy making and communication by CIFs.

3. Beaten by more determined competitors

All WIFs acquired, or made attempts to acquire the market leaders in China. However, in subsequent competitions, CIFs simply showed stronger determination to survive at any costs.

"In the case of Uber, it was not simply a matter of what Uber did wrong, but what Didi Chuxing did better," said Professor Li.

When Uber entered China, Didi already had a head start. Despite the perceived competitive advantages for Uber, Didi was simply more determined, with more cash reserves than Uber for a prolonged price war. In many ways, the competition between them was reminiscent of the reckless land grabbing during the early dot.com era, but the difference is that both firms have the resources and long term visions to capture market shares first before making profits. In the end, Uber blinked first and lost.

4. New digital rules: differences between internet and traditional businesses

Some fundamental differences between internet and traditional businesses contributed to the failure of WIFs in China, and this factor was only identified by the outside view. Internet services usually have a much shorter lifecycle compared with traditional industries; and WIFs only have 2-3 years rather than decades to fine-tune their business models and educate customers. This limited the build-up of any sustainable advantages by WIFs and gives Chinese internet firms a much better chance to compete with them than in traditional industries.

"Car engines are far more difficult to imitate than search engines," commented Professor Li.

Unlike aerospace or pharmaceuticals, most internet firms do not rely on cutting edge technologies so the entry barriers are relatively low. Ancillary assets and tacit knowledge embedded in production processes and supply chains in traditional industries also serve as major entry barriers. As a result, WIFs have fewer competitive advantages and face far more competitors than western firms from other sectors.

5. Failing to be embedded in China

All the WIFs studied showed a lack of deep understanding of the Chinese market. They found it difficult to compete with Chinese entrepreneurs in serving the local market. This is not only reflected in understanding users and customers, but also internally within the firms. Senior expatriates sent from the western head office often lacked cultural sensitivity, thus damaging relations without realising it.

6. Innovating by experimenting

Unlike WIFs which have established procedures for developing and implementing innovations, Chinese Internet Firms (CIFs) are often more result-oriented and more prepared to innovate by experimenting. Li added, "If a new idea works, then scale it up rapidly; if not, move onto other ideas".

Chinese consumers are generally more tolerant of such product development processes than in the West, which enable CIFs to test and refine many new ideas very quickly at low cost, with significant cumulative effects.

Success in the future?

WIFs have underperformed compared to their Chinese competitors in nearly every aspect in
China, but their disadvantages are not insurmountable. To succeed in China, WIFs need to bring
genuine technological and other advantages in order to overcome, or compensate for, their disadvantages.

Professor Li concluded, "As CIFs grow bigger and more confident, they are actively pursuing new opportunities in other markets - from India, South East Asia, Africa to the USA and Europe - so the clashes between digital firms in each market are likely to escalate both in China and internationally."

'Why have all western internet firms (WIFS) failed in china? A phenomenon-based research' and has been published in the Academy of Management Discoveries.

Credit: 
City St George’s, University of London

Epidemiologists link acetaminophen use during pregnancy to autism and ADHD risk

A study from the Hebrew University of Jerusalem sheds new light on the possible relationship between prolonged use of acetaminophen (paracetamol) during pregnancy and the risk of neurodevelopmental disorders in childhood.

Acetaminophen is one of the most common medications used for treatment of pain and fever reduction during pregnancy and is considered safe in humans. However, evidence of neuro-disruptive properties is accumulating: past studies have shown that long-term administration of low doses of acetaminophen may affect the development of the fetal nervous system, and that this effect is often seen years after exposure during childhood.

Now, researchers led by Dr. Ilan Matok at the Institute for Drug Research in the School of Pharmacy at the Hebrew University's Faculty of Medicine, together with doctoral student Reem Masarwa, have conducted a systematic review and meta-analysis to assess the possible association between prolonged exposure to acetaminophen during pregnancy and the risk for attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD).

The analysis, which appears in the American Journal of Epidemiology, shows that prolonged exposure to acetaminophen during pregnancy is associated with a 30% increase in relative risk for ADHD (compared to those who did not take acetaminophen during pregnancy) and a 20% increase in relative risk for ASD.

This is the first meta-analysis and the most comprehensive study ever conducted on the possible association between prolonged use of acetaminophen during pregnancy and risk of autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD). The research data covered 132,738 mother and child pairs with a follow-up period of 3-11 years.

Given the significant limitations of existing studies, the researchers believe the results should be interpreted with caution, as they may cause unnecessary anxiety among pregnant women. It is important to understand that pain and fever during pregnancy can have a detrimental effect on the developing fetus and that acetaminophen is still considered a safe drug for use during pregnancy. Therefore, if a pregnant woman has fever and/or pain, acetaminophen can be taken for a short period, and if the fever or pain continue beyond that, she should consult her physician regarding further treatment

Dr. Amichai Perlman and Dr. Hagai Levine of the Hebrew University of Jerusalem and Hadassah Medical Center participated in the research.

"Our study provides the first comprehensive overview of developmental outcomes following prolonged acetaminophen use during pregnancy," said Dr. Ilan Matok, Head of the Pharmacoepidemiology Research Lab, Institute for Drug Research, School of Pharmacy, Hebrew University Faculty of Medicine. "Our findings suggest an association between prolonged acetaminophen use and an increase in the risk of autism and ADHD. However, the observed increase in risk was small, and the existing studies have significant limitations. While unnecessary use of any medication should be avoided in pregnancy, we believe our findings should not alter current practice and women should not avoid use of short term acetaminophen when clinically needed."

Credit: 
The Hebrew University of Jerusalem

How do you get teens to stop cellphone use while driving? Survey says, show them the money

PHILADELPHIA - Teens who admit to texting while driving may be convinced to reduce risky cellphone use behind the wheel when presented with financial incentives such as auto-insurance apps that monitor driving behavior, according to a new survey conducted by researchers at the Perelman School of Medicine at the University of Pennsylvania and Children's Hospital of Philadelphia (CHOP). However, while more than 90 percent of teens surveyed said they were willing to give up sending or reading text messages, almost half indicated that they would want to retain some control over phone functions such as music and navigation. Results of the survey are published in the journal Traffic Injury Prevention.

"More than half of teens in the United States admit to texting while driving, and this has become a significant public health issue leading to preventable deaths and disabling injuries," said study lead author Kit Delgado, MD, an assistant professor of Emergency Medicine at Penn. "Our study suggests a promising strategy to curb this epidemic would include enabling a phone setting or third party app with automatic responses to incoming texts, but with navigation and music functions accessible, combined with financial incentives to sustain use."

For example, Delgado suggests this could be accomplished by enabling the 'Do Not Disturb While Driving' setting on an iPhone to automatically turn on while the car is in motion and enrolling in an auto insurance program that offers financial incentives for using apps to track driving behavior, which have begun to emerge in the past year.

Car crashes are the leading cause of death for American teens, and as cellphone use has become ubiquitous over the past two decades, texting while driving has become a significant factor in these accidents. Today, drivers 15- to 19-years-old are more likely than any other age group to die in crashes caused by cellphone-related distractions.

The National Highway Traffic Safety Administration (NHTSA) has recommended a "Driver Mode" on smartphones--similar to the existing "Airplane Mode"--to limit use while driving. Since last year, the operating system for iPhones, iOS, has had a "Do Not Disturb While Driving" mode that locks the phone screen, blocks incoming texts and sends automatic text responses, and limits incoming phone calls. But, the settings are optional. To better understand the barriers to widespread teen adoption of cellphone-limiting strategies, he and his colleagues decided to ask some teens.

"Apps and settings aimed at reducing cellphone distraction while driving can only be effective from a population health standpoint if they are widely adopted," Delgado said.

The researchers contacted the parents of adolescents who had previously been seen across the CHOP Care Network, and invited them to sign up their 16- and 17-year olds for a survey. The investigators ultimately received survey responses from 153 teens who met the study criteria, which included texting while driving in the past month and driving their own car.

The vast majority of the teens indicated that they were "willing" or "somewhat willing" to give up reading emails (99 percent), social media apps (99 percent), sending texts (96 percent), reading texts (91 percent), and making or receiving non-hands-free calls (94 and 91 percent, respectively) while driving. Far fewer of them were willing or somewhat willing to give up music apps (55 percent) or navigation apps (40 percent).

About half of the teens in the sample reported "high frequency" texting while driving - defined as more than six days per month. These teens showed markedly less willingness to give up cellphone uses while driving. For example, 73 percent indicated they were unwilling to give up navigation apps compared with just 44 percent of the overall sample.

The researchers asked the survey participants to consider several possible factors or strategies that could discourage them from texting while driving, such as an annual insurance premium discount, or a cash reward for every week in which they don't text and drive. Most of the teens indicated that financial incentives would be "very effective," but many (54 percent) also indicated that automatic phone locking while driving would work.

All in all, the findings suggest that teens might widely and voluntarily adopt a "Driver Mode" app or phone setting that automatically blocks or limits text and call functions while allowing navigation and music functions, especially if combined with a financial incentive.

"One scalable way to provide a financial incentive would be to offer teens auto insurance discounts, based on actual driving performance and phone use as measured by in-vehicle devices or smartphone apps, which are becoming more common and hold tremendous promise with the shift to usage-based insurance (UBI)," Delgado said. "These programs adjust insurance premiums and provide financial incentives based on directly observed driving behaviors. Our research team is currently conducting studies aimed at figuring out how to design UBI programs to sustainably reduce handheld cellphone use while driving."

It's estimated that there are 16 million UBI subscribers currently in the U.S., which will increase to 60 million by 2023. Furthermore, Delgado says the industry is shifting from in-vehicle devices to smartphone apps that can now directly measure cellphone use while driving.

When asked why they wouldn't want to use cellphone apps that monitor driving behavior, the survey participants cited an aversion to letting parents monitor their behavior - which they believed such apps would facilitate - as their top reason. A modest financial incentive may be enough to outweigh such concerns, Delgado said, though he noted that "we need a better understanding of how to design interventions that optimally balance parental
engagement and acceptance by teens."

Credit: 
University of Pennsylvania School of Medicine

New vaccine could help people overcome bath salts abuse

Researchers have developed a vaccine for one of the most dangerous types of synthetic cathinones, or bath salts. The vaccine blunts the illegal stimulant's effects on the brain, which could help recovering drug users who experience a relapse.

Samantha McClenahan, a doctoral student at the University of Arkansas for Medical Sciences, will present test results for the new vaccine at the American Society for Pharmacology and Experimental Therapeutics annual meeting during the 2018 Experimental Biology meeting to be held April 21-25 in San Diego.

Synthetic cathinones are stimulants made to mimic the stimulate effects found in the khat plant. The most powerful compounds in this drug class can produce deadly overdoses as well as life-threatening side effects such as organ failure.

The new vaccine targets two very potent synthetic cathinones known as methylenedioxypyrovalerone (MDPV) and alpha-pyrrolidinovalerophenone (alpha-PVP). "Because the chemical structures of these illegal drugs are often changed to evade drug laws, we decided it was important to develop a single vaccine that will be effective against more than one medically dangerous synthetic cathinone," said McClenahan. Results from the new study showed that rodents receiving the vaccine produced high amounts of antibodies that attached tightly to MDPV and alpha-PVP in the blood stream. This immune response was able to decrease the stimulant effects of MDPV for months. The researchers observed that vaccinated rats exhibited significantly less MDPV-induced movement and significantly shortened MDPV-induced activity compared to untreated rats.

"Our goal is to develop a vaccine that would be effective for at least 6 to 12 months so that it could be used as a long-lasting aid to the rehabilitation process," said McClenahan. "It would likely help reduce drug concentrations in critical organs and reduce or eliminate the rewarding effect of the drug. This could improve the chances of an individual remaining in rehabilitation treatment, which might increase the likelihood of a successful outcome."

The researchers plan to continue to test the vaccine's ability to prevent the entry of MDPV into the brain and heart, which causes the rewarding effects of the drug and is a leading cause of the drug's dangerous side effects. This research was supported by National Institute on Drug Abuse grant RO1DA039195 and NIH training grant T32GM106999. Samantha McClenahan will present this research at 12:30-2:30 p.m. Sunday, April 22, Exhibit Halls A-D, San Diego Convention Center (poster C20 550.7) (abstract) and at 11:50 a.m. Tuesday, April 24 during the Simulants I Session (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

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Experimental Biology

Growing evidence that probiotics are good for your liver

Increased awareness of the importance of the microbes that live in our gut has spurred a great deal of research on the microbiome and fueled a booming probiotics industry. A new study suggests probiotics can improve not only the health of our gut but liver health, as well.

"Probiotics have been studied most intensely in the context of the gastrointestinal tract," said Bejan Saeedi, a doctoral candidate at Emory University who conducted the research. "This study provides evidence that the effects of probiotics extend beyond the gastrointestinal tract. What makes this study unique is that it suggests a discreet molecular mechanism by which these effects are elicited."

Saeedi will present the research at the American Society for Investigative Pathology annual meeting during the 2018 Experimental Biology meeting, held April 21-25 in San Diego.

The vast populations of microbes that reside on and inside of our bodies have been shown to play a role in numerous functions that keep our bodies healthy. Probiotics are bacteria that are consumed or administered in an effort to boost the populations of these beneficial microbes.

Saeedi and his colleagues focused their study on the probiotic Lactobacillus rhamnosus GG (known as LGG), a species common in many over-the-counter probiotic formulations. They gave mice food laced with LGG for two weeks and then examined how they responded to a high dose of acetaminophen (the active ingredient in Tylenol®).

Taking too much acetaminophen can cause serious liver damage and even death by increasing the abundance of a form of oxygen called free radicals, a process known as oxidative stress. However, the researchers found that mice receiving the probiotic treatment suffered less liver damage when presented with an overdose of acetaminophen compared with mice that did not receive probiotics.

"Administration of the probiotic LGG to mice improves the antioxidant response of the liver, protecting it from oxidative damage produced by drugs such as acetaminophen," explained Saeedi.

The liver is a hub for removing toxins from the blood and plays an important role in the body's processes for converting food into energy. Since it is "downstream" of the gastrointestinal tract in the digestive process, it makes sense that the composition of bacteria in the gut could affect the functioning of the liver.

Previous research by Saeedi's colleagues has traced the molecular process by which LGG appears to protect against oxidative liver injury. That research points to the role of a protein called Nrf2, which regulates the expression of genes involved in fighting free radicals.

Other studies in mice have previously shown that LGG can protect against alcoholic liver disease and non-alcoholic fatty liver disease. Saeedi said studies in human volunteers would be needed to definitively test the potential clinical benefits of LGG in humans.

Bejan Saeedi will present this research on Sunday, April 22, from 2:45-3 p.m. in Room 4, San Diego Convention Center (abstract) and on Tuesday, April 24, from 5:30-7:30 p.m. in Ballroom 20BC (poster 150.4). Contact the media team for more information or to obtain a free press pass to attend the meeting.

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Experimental Biology

Researchers report four new insights into diet and health

What we eat plays a significant role in our health. The Experimental Biology 2018 meeting (EB 2018) will showcase new research into how diet could be used to fight cancer and how specific eating patterns can encourage weight loss.

Time-restricted eating reduces tumor growth in mice

Obesity is known to increase the risk for breast cancer, particularly in postmenopausal women. With a long-term goal of developing practical strategies to curb breast cancer risk, researchers from the University of California, in San Diego, examined how restricting eating to a certain number of hours each day might affect cancer. For the study, obese mice modeling the postmenopausal life stage were either given access to high-fat food 24 hours a day or restricted to eating the high-fat food during 8 active hours, simulating daytime eating in people. After 3 weeks, the mice were injected with breast cancer cells. Although the overall quantity of food consumed differed little between the two groups, the time-restricted eating group showed reduced tumor growth as well as better glucose tolerance and insulin resistance, which are both linked to blood sugar control. Additional experiments showed that tumor growth was insulin-dependent, suggesting that time-restricted feeding may act by lowering insulin signaling.

Manasi Das will present this research at the American Society for Biochemistry and Molecular Biology annual meeting during the Obesity, Metabolism and Immune Cells in Cancer session at 4:30 p.m. Monday, April 23, in Room 31A (abstract) and at 12:45 p.m. Tuesday, April 24, in Exhibit Halls A-D (poster B491 811.19).

Adults who eat breakfast gain less weight

Although studies have shown an association between eating breakfast and healthy body weight in children and teenagers, less research has focused on this relationship in adults. In an analysis involving 347 healthy adults, researchers from the Mayo Clinic found that study participants who skipped breakfast were more likely to be obese than those who ate it frequently, defined as five to seven times a week. Participants who skipped breakfast also had larger waists than those who ate breakfast frequently or infrequently (one to four times a week). The link between skipping breakfast and weight gain remained even after the researchers took into account age, gender and body mass index. People who did not eat breakfast reported the most weight gain over the past year, and those who consumed breakfast on most days reported the lowest weight gain. The researchers conclude that regularly consuming breakfast is important for maintaining a healthy weight at all ages.

Kevin Smith will present this research at the American Physiological Society (APS) annual meeting from 10 a.m.-12 p.m. Sunday, April 22, in Exhibit Halls A-D (poster A324) (abstract).

Alternate-day fasting enhances weight loss in obesity-prone rats

When a person is losing or maintaining recently lost weight, energy expenditure during rest and activity tends to decrease as the body's metabolism gradually slows. In a new study, Kent State University researchers examined how alternate-day fasting -- a diet that restricts calories every other day -- affects energy expenditure. They placed lean and obese-prone mice on every-day calorie restriction or alternate-day fasting aimed at equivalent weight loss and then measured energy expenditure during treadmill walking. Although the obesity-prone and lean mice on both diets showed a similar decrease in activity-associated energy expenditure, the obesity-prone mice on the alternate-day fasting diet lost significantly more weight than the lean mice. There was also no difference in activity-associated energy expenditure on fasting and non-fasting days. The results suggest that weight loss effects from alternate-day fasting might also vary in people.

Amber Titus will present this research at the APS annual meeting at 10 a.m.-noon Sunday, April 22, in Exhibit Halls A-D (poster A323 604.1) (abstract).

New insights into taste perception

Conditions inside the mouth such as temperature can affect our perception of taste. Interactions between taste and the general sensitivity of the mouth to pungency, irritation or heat were thought to result from indirect interactions between taste cells and neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P. In a new mouse study, researchers from the Southern Illinois University School of Medicine used a combination of functional imaging and cellular biosensors to show that neuropeptides play a more direct regulatory role in processing taste signals. The study results suggest that substance P and CGRP act as inhibitory neurotransmitters that shape the signals traveling from taste buds to the brain. The discovery of this unanticipated route of taste sensory information flow could aid in the development of taste modifiers for potential use in managing obesity or new treatments for taste problems that develop as a side effect of chemotherapy drugs.

Anthony Huang will present this research at the American Association of Anatomists annual meeting during the Role of Neuropeptides in Peripheral Taste Signaling session at 9:15 a.m. Tuesday, April 24, in Room 11B (abstract).

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Experimental Biology

Endangered salamander offers clues on healing spinal cord injury

image: The axolotl, also known as the Mexican salamander, shows a remarkable ability to regenerate nerves after damage.

Image: 
Karen Echeverri, University of Minnesota.

One of the most vexing problems with spinal cord injuries is that the human body does not rebuild nerves once they have been damaged. Other animals, on the other hand, seem to have no problem repairing broken neurons.

A new study takes a comparative approach to pinpoint what happens differently in humans versus other animals to explain why they can successfully regenerate neurons while we instead form scar tissue. By learning from the similarities and differences, researchers hope to find new leads in the treatment of spinal cord injury.

"Humans have very limited capacity for regeneration, while other species like salamanders have the remarkable ability to functionally regenerate limbs, heart tissue and even the spinal cord after injury," said lead researcher Karen Echeverri, PhD, assistant professor in the department of genetics, cell biology and development at the University of Minnesota. "We have discovered that despite this difference in response to injury, these animals share many of the same genes with humans. This knowledge could be used to design new therapeutic targets for treating spinal cord injury or other neurodegenerative diseases."

Echeverri will present the research at the American Association of Anatomists annual meeting during the 2018 Experimental Biology meeting, held April 21-25 in San Diego.

Echeverri and her colleagues study an amphibian known as the axolotl or Mexican salamander. Native to lakes near Mexico City, the axolotl has become endangered in the wild as human activities have encroached on its habitat. Captive-bred axolotls are frequently used in biological research, both to learn from the animal's remarkable ability to regenerate body parts and to help inform conservation efforts.

When an axolotl suffers a spinal cord injury, nearby cells called glial cells kick into high gear, proliferating rapidly and repositioning themselves to rebuild the connections between nerves and reconnect the injured spinal cord. By contrast, when a human suffers a spinal cord injury, the glial cells form scar tissue, which blocks nerves from ever reconnecting with each other.

Echeverri's team traced the molecular mechanisms at work in each case. They found a particular protein called c-Fos, which affects gene expression, is essential to the processes axolotls use to repair injured nerves. While humans also have c-Fos, in humans the protein functions in concert with other proteins, in the JUN family, that cause cells to undergo reactive gliosis, which leads to scar formation. In axolotls, this molecular circuitry is carefully regulated to direct axolotl glial cells toward a regenerative response instead.

"Our approach allows us to identify not just the mechanisms necessary to drive regeneration in salamanders but what is happening differently in humans in reposes to injury," said Echeverri, adding that the work has implications for other types of injury, as well. "In addition to spinal cord regeneration, our work also focuses on other forms of regeneration including scar-free wound healing and limb regeneration."

Karen Echeverri will present this research on Sunday, April 22, from 3-3:30 p.m. in Room 11B, San Diego Convention Center (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

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Experimental Biology

Brainy new approaches to autism, chronic pain, concussion and more

Technological advances have ushered in a new era of discovery in neuroscience. The Experimental Biology 2018 meeting (EB 2018) will feature an array of research findings on the brain and nervous system. The studies shed new light on the intricate circuitry behind our thought processes, feelings and behaviors and offer leads for both high-tech and low-tech treatment approaches.

Innovative nanocapsules could improve delivery of drug for Autism Spectrum Disorder

The hormone oxytocin has been shown to be helpful for improving social interactions in people with Autism Spectrum Disorder and other neurological conditions. However, its effects are very short term because the hormone breaks down quickly in the bloodstream and cannot cross the blood-brain barrier to enter the brain. A team of scientists at Mercer University have developed tiny capsules to shuttle oxytocin across the blood-brain barrier and slow its degradation. In experiments conducted in cells and mice, the nanocapsules appear to last longer and engender stronger prosocial effects than oxytocin alone. If successful in humans, the technology could improve autism treatment and potentially be applied to other drugs aimed at treating seizures, inflammation and other neurological problems.

Kevin Murnane will present this research at the American Society for Pharmacology and Experimental Therapeutics annual meeting at EB on Tuesday, April 24, from 12:30-2:30 p.m. in the Exhibit Hall (poster C121) (abstract).

Rabies and herpes viruses harnessed for new brain circuit mapping

Researchers from the University of California, Irvine are using a surprising technique to make new discoveries about the layout of the brain's center for learning, memory and spatial navigation. Although the hippocampus has been well studied, traditional mapping techniques do not provide information about specific cell types or the relative strengths of the connections between neurons. To take a closer look at how different areas of the hippocampus interact, the researchers injected the brains of live mice with viruses including rabies and herpes simplex virus. The scientists then traced the viruses as they replicated within neurons and spread from cell to cell, typically by jumping across the synapses that link neurons to each other. The researchers also induced specific neurons to fire and analyzed behavioral changes in the mice. Taken together, the experiments provide new insights about the hippocampus and, in particular, how two segments of it interact to regulate learning and memory.

Xiangmin Xu will present this research at the American Association of Anatomists annual meeting at EB on Sunday, April 22, from 4-4:30 p.m. in Room 11A (abstract). Images available.

Fighting pain by tracking it back to its place of origin

There is still much scientists do not understand about how the body transmits and regulates pain signals. Researchers at Texas A&M are taking a detailed look at the thalamus, a part of the brain where most pain signals are processed, in hopes of finding new treatments for chronic pain that do not have the side effects or addiction potential of existing therapies like opioids and other drugs. The team has engineered mice that produce glowing proteins when pain-activated neurons fire and used genetically modified rabies virus as a tracer to mark how pain signals travel from neuron to neuron. By combining these techniques, the team has been able to create a brain-wide map of the neurons that feed pain signals into the thalamus, illuminating specific areas that might be targeted with new therapeutics.

Mikhail Umorin will present this research at the American Association of Anatomists annual meeting at EB on Sunday, April 22, from 5-5:30 p.m. in Room 11A (abstract).

Exercise after concussion appears to aid recovery

Doctors generally recommend refraining from exercise after a concussion (a type of brain injury typically caused by a blow to the head) in order to let the brain heal. However, a new study from the University of Western Ontario suggests that moderate aerobic exercise can be helpful for patient recovery and "return-to-sport" decisions. Among other symptoms, concussions can have effects on the heart rate, including increased heart rate and reduced heart rate variability, meaning that the heart rate stays high and doesn't rise and fall as it normally would in response to exertion. In the study, researchers randomly assigned seven teenage participants to three sessions of moderate exercise over the course of a week following a concussion, stopping short of a level of exertion that would exacerbate their headache or other symptoms. Eight other concussed teens were assigned to refrain from exercise for the week. Before-and-after tests revealed those who had exercised showed significant improvements in measures of heart rate and variability, indicating a quicker recovery, compared to those who had simply rested.

Alexandra Harriss will present this research at the American Physiological Society annual meeting at EB on Tuesday, April 24, from 10 a.m.-noon in the Exhibit Hall (poster A505) (abstract).

EB 2018 is the premier annual meeting of five scientific societies to be held April 21-25 at the San Diego Convention Center. Contact the media team for abstracts, images and interviews, or to obtain a free press pass to attend the meeting.

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Experimental Biology