Brain

Optimistic Latinos have healthier hearts, study finds

image: Latinos who are the most optimistic are more likely to have healthy hearts, suggests a new study led by University of Illinois social work professor Rosalba Hernandez.

Image: 
Photo by L. Brian Stauffer

CHAMPAIGN, Ill. -- Latinos who are the most optimistic are more likely to have healthy hearts, suggests a new study of more than 4,900 people of Latino/Hispanic ancestry living in the U.S.

"Each unit increase in a Latino adult's level of optimism was associated with 3 percent higher odds of meeting the criteria for ideal cardiovascular health across four or more metrics," said principal investigator Rosalba Hernandez, a professor of social work at the University of Illinois. "The correlation between optimism and cardiovascular health was consistent across heritage groups, regardless of age, sex, nativity status or level of acculturation."

Few of the individuals who scored low in optimism met the criteria for ideal heart health, Hernandez and her co-authors found. However, each percentage point increase in optimism was associated with a better cardiovascular health score.

The current study was one of the first to explore associations between emotional well-being and cardiac health in a large diverse sample of Hispanic/Latino adults.

While numerous prior studies -- including a 2015 study by Hernandez -- found links between a positive mental outlook and cardiovascular health, the samples in those studies contained primarily Latinos of Mexican descent, Hernandez said.

To explore whether the effect persisted across heritage groups, Hernandez's study used a sample that was much more diverse.

Latinos of Mexican heritage composed more than 37 percent of the participants, followed by Latinos of Cuban descent (20 percent), Puerto Rican (15.5 percent), Dominican (11.5 percent), Central American (7.4 percent) and South American (4.7 percent) ancestries.

Participants' cardiovascular health was assessed using the American Heart Association's "Life's Simple 7" metrics, which include blood pressure, body mass index, fasting plasma glucose and serum cholesterol levels, dietary intake, physical activity and tobacco use.

Individuals' level of dispositional optimism -- their expectation that good things will happen in the future -- was measured using the Life Orientation Test-Revised. The test asks participants how much they agree with statements such as, "In uncertain times, I usually expect the best." Possible scores range from six (least optimistic) to 30 (most optimistic).

Levels of optimism differed by ancestry, Hernandez and her co-authors found. Latinos of Cuban and Central American heritage were the most optimistic, while Latinos of Mexican and Puerto Rican heritage were the least likely to be positive thinkers.

Latinos with the highest levels of optimism also tended to be older, married or living with a partner, better educated and more affluent, the researchers found.

According to the Centers for Disease Control and Prevention, Latinos born outside the U.S. have 50 percent lower rates of cardiovascular disease compared with Latinos who are born in the U.S. Tapping into psychological assets such as optimism may provide effective, low-cost strategies for improving the cardiovascular health of some of these Latino populations, according to the study.

"Problems with access to health care, affordability and the shortage of psychologists and psychiatrists who speak Spanish are significant challenges for Latino populations in the U.S.," Hernandez said. "We need to find accessible, cost-effective ways of utilizing technology to help vulnerable populations."

In a related project, Hernandez is examining whether individuals with high blood pressure can be taught to be more optimistic and if greater optimism in turn moderates participants' hypertension. Both that project and the current study were funded by the National Heart, Lung and Blood Institute.

"We don't know much about the connections between emotional and physical health," Hernandez said. "However, if we can identify certain strengths within a population that can be used to improve their health, that would be fantastic."

The sample for the current study was drawn from the Sociocultural Ancillary Study, which explored socioeconomic, cultural and psychosocial influences on Latinos' health. That study was part of a larger project called the Hispanic Community Health Study/Study of Latinos, conducted from 2008 to 2011, which included more than 16,400 Latinos living in California, Florida, Illinois and New York.

Credit: 
University of Illinois at Urbana-Champaign, News Bureau

Decade of fossil collecting gives new perspective on Triassic period, emergence of dinosaurs

image: The skull of a gorgonopsian, a distant mammal relative and top predator during its pre-dinosaur era about 255 million years ago. This fossil was collected in 2009 in Zambia.

Image: 
Christian Sidor/University of Washington

After a great mass extinction shook the world about 252 million years ago, animal life outside of the ocean began to take hold. The earliest mammals entered the scene, and reptiles -- including early dinosaurs -- lived on Pangea, the name given to the giant landmass in which all of the world's continents were joined as one.

A project spanning countries, years and institutions has attempted to reconstruct what the southern end of this world looked like during this period, known as the Triassic (252 to 199 million years ago). Led by paleontologists and geologists at the University of Washington, the team has uncovered new fossils in Zambia and Tanzania, examined previously collected fossils and analyzed specimens in museums around the world in an attempt to understand life in the Triassic across different geographic areas.

Findings from the past decade of fieldwork and analysis are reported in a publication of the Society of Vertebrate Paleontology, appearing online March 28. In total, 13 research papers detailing new fossils, geologic discoveries and ecological findings in the Triassic make up the society's 2018 special-edition volume, published once a year in a competitive submission process.

"Most of what we know about the major mass extinction is from the South African Karoo Basin. I was always interested in understanding, do we see the exact same pattern around the world, or do we not?" said co-editor Christian Sidor, a UW biology professor and curator of vertebrate paleontology at the Burke Museum of Natural History and Culture.

"The fossil record can be great to understand timing and sequence, but not always great at looking at things in a geographic context."

Since 2007, Sidor and his team of students, postdoctoral researchers, paleontologists and geologists have visited the Ruhuhu Basin of Tanzania five times and the Luangwa and mid-Zambezi basins of Zambia four times. They lived there for about a month at a time, often hiking for miles to find fossil sites and camping in villages and national parks. Once, they were even awakened by the stomping and calls of elephants only feet from their camp.

Each site in Tanzania and Zambia contains its own collection of fossils from the Triassic and other periods, but the goal of this decade-long project was to look across locations hundreds and thousands of miles apart to find similarities in the fossil records. Two papers describe the regional patterns and similarities across much of what used to be Pangea.

"These papers highlight what a regional perspective we now have -- we have the same fossils from Tanzania, Antarctica, Namibia and more," Sidor said. "We're getting a much better Southern Hemisphere perspective of what's going on in the Triassic."

Most of the papers in the special edition discuss new fossil findings from the paleontological digs. One explains the discovery of a new species of lizard-like reptile called a procolophonid. Another details Teleocrater, an early dinosaur relative that walked on four crocodile-like legs. This finding was reported in Nature last year, but the new paper describes the animal's anatomy in fuller detail.

Most of the remaining papers describe other animals that were present in the Triassic besides the early dinosaurs.

"This was a time when dinosaurs were just stepping onto the stage, and they were not very big and not very remarkable animals then," Sidor said. "These papers really round out what dinosaurs were competing with before they became the dominant reptiles on land."

In addition to the 13 papers that make up the special edition, the team has published 24 peer-reviewed papers as part of this project in the past decade.

More than 2,200 fossils were collected across Tanzania and Zambia over the last decade of fieldwork. Of the special edition's 27 authors, many participated in fieldwork with Sidor since 2007, including co-editor Sterling Nesbitt, a former postdoctoral researcher at the UW and now an assistant professor at Virginia Tech.

Fossil hunting is an experience every member of Sidor's lab can have, from undergraduates through postdoctoral researchers. Sidor and a team are going again this August.

"This has been what my lab has done, and all of my students have been involved in some way," he said. Four of Sidor's students and two postdoctoral researchers are co-authors of papers in the new special edition.

Credit: 
University of Washington

Prosthetic memory system successful in humans, study finds

video: Scientists at Wake Forest Baptist Medical Center and the University of Southern California have demonstrated the successful implementation of a prosthetic memory system in humans.

Image: 
Wake Forest Baptist Medical Center

WINSTON-SALEM, N.C. - March 28, 2018 - Scientists at Wake Forest Baptist Medical Center and the University of Southern California (USC) have demonstrated the successful implementation of a prosthetic system that uses a person's own memory patterns to facilitate the brain's ability to encode and recall memory.

In the pilot study, published in today's Journal of Neural Engineering, participants' short-term memory performance showed a 35 to 37 percent improvement over baseline measurements. The research was funded by the U.S. Defense Advanced Research Projects Agency (DARPA).

"This is the first time scientists have been able to identify a patient's own brain cell code or pattern for memory and, in essence, 'write in' that code to make existing memory work better, an important first step in potentially restoring memory loss," said the study's lead author Robert Hampson, Ph.D., professor of physiology/pharmacology and neurology at Wake Forest Baptist.

The study focused on improving episodic memory, which is the most common type of memory loss in people with Alzheimer's disease, stroke and head injury. Episodic memory is information that is new and useful for a short period of time, such as where you parked your car on any given day. Reference memory is information that is held and used for a long time, such as what is learned in school.

The researchers enrolled epilepsy patients at Wake Forest Baptist who were participating in a diagnostic brain-mapping procedure that used surgically implanted electrodes placed in various parts of the brain to pinpoint the origin of the patients' seizures. Using the team's electronic prosthetic system based on a multi-input multi-output (MIMO) nonlinear mathematical model, the researchers influenced the firing patterns of multiple neurons in the hippocampus, a part of the brain involved in making new memories in eight of those patients.

First, they recorded the neural patterns or 'codes' while the study participants were performing a computerized memory task. The patients were shown a simple image, such as a color block, and after a brief delay where the screen was blanked, were then asked to identify the initial image out of four or five on the screen.

The USC team led by biomedical engineers Theodore Berger, Ph.D., and Dong Song, Ph.D., analyzed the recordings from the correct responses and synthesized a MIMO-based code for correct memory performance. The Wake Forest Baptist team played back that code to the patients while they performed the image recall task. In this test, the patients' episodic memory performance showed a 37 percent improvement over baseline.

In a second test, participants were shown a highly distinctive photographic image, followed by a short delay, and asked to identify the first photo out of four or five others on the screen. The memory trials were repeated with different images while the neural patterns were recorded during the testing process to identify and deliver correct-answer codes.

After another longer delay, Hampson's team showed the participants sets of three pictures at a time with both an original and new photos included in the sets, and asked the patients to identify the original photos, which had been seen up to 75 minutes earlier. When stimulated with the correct-answer codes, study participants showed a 35 percent improvement in memory over baseline.

"We showed that we could tap into a patient's own memory content, reinforce it and feed it back to the patient," Hampson said. "Even when a person's memory is impaired, it is possible to identify the neural firing patterns that indicate correct memory formation and separate them from the patterns that are incorrect. We can then feed in the correct patterns to assist the patient's brain in accurately forming new memories, not as a replacement for innate memory function, but as a boost to it.

"To date we've been trying to determine whether we can improve the memory skill people still have. In the future, we hope to be able to help people hold onto specific memories, such as where they live or what their grandkids look like, when their overall memory begins to fail."

The current study is built on more than 20 years of preclinical research on memory codes led by Sam Deadwyler, Ph.D., professor of physiology and pharmacology at Wake Forest Baptist, along with Hampson, Berger and Song. The preclinical work applied the same type of stimulation to restore and facilitate memory in animal models using the MIMO system, which was developed at USC.

Credit: 
Atrium Health Wake Forest Baptist

On cryptocurrency exchanges, it's better to be a miner than a speculator, study finds

Someone who starts mining a crypto-currency shortly after it is listed on exchanges can potentially earn higher returns than average. But a speculator who enters the market shortly after the currency is listed might potentially earn lower returns.

These are some of the findings from a study where computer scientists estimated the potential profitability of mining versus speculating for 18 crypto-currencies that are not Bitcoin and Litecoin--known under the general label of altcoin. Computer scientists also showed that returns from mining a random altcoin tend to be less risky to earn than returns from speculation.

"It's also important to point out that we show the Altcoin market is highly volatile, whether you're mining or speculating," said Danny Huang, first author of the paper, who earned his Ph.D. in computer science at the University of California San Diego and is now postdoctoral researcher at Princeton.

Researchers used real-world blockchain and trade data for the study. They arrived at these conclusions by comparing mining and speculating for the 18 altcoins against Bitcoin and Litecoin using opportunity cost to estimate potential profits for miners and speculators.

They also designed simulations to estimate the daily returns per $1 of investment, either through mining or speculating, under various conditions. They found that for seven days, expected daily returns ranged from 7 to 18 percent for mining and negative 1 percent to positive 0.5 percent for speculating.

The researchers presented their results at the Financial Crypto 2018 conference Feb. 26 to March 2 in the Caribbean.

For every dollar invested in mining or buying a coin, researchers computed the potential returns under various conditions, such as time of market entry and hold positions. While some coins offer the potential for spectacular returns, many follow a simple bubble-and-crash scenario, which highlights the extreme risks -- and potential gains -- in altcoin markets.

Digital currencies have flourished in recent years, buoyed by the tremendous success of Bitcoin. These blockchain-based currencies are associated with a few thousand to millions of dollars of market capitalization.

"Altcoins have attracted enthusiasts who enter the market by mining or buying them, but the risks and rewards can potentially be significant, especially when the market is volatile," Huang said.

Credit: 
University of California - San Diego

OU study reveals trends of US surface water body area over three decades

image: This is the Lake Thunderbird reservoir in Norman, Oklahoma.

Image: 
University of Oklahoma

A University of Oklahoma research study, led by Professor Xiangming Xiao, reveals the divergent trends of open surface water bodies in the contiguous United States from 1984 to 2016, specifically, a decreasing trend in the water-poor states and an increasing trend in the water-rich states. Surface water resources are critical for public water supply, industry, agriculture, biodiversity and ecosystem services.

"The data, information and knowledge on long-term trends of surface water bodies across the CONUS at high spatial resolution are valuable for planning and management of surface water resources, however, they are not widely available yet," said Xiao, professor of ecology and remote sensing in the Department of Microbiology and Plant Biology, OU College of Arts and Sciences.

Xiao and his team analyzed approximately 370,000 Landsat images and generated annual surface water body frequency maps for 1984 to 2016 at 30-m spatial resolution. Zhenhua Zhou, first author on the study and one of Xiao's graduate students, says, "Google's Earth Engine cloud computing platform, freely available Landsat image data, together with the novel and robust mapping algorithms derived from years of remote sensing studies in the past allowed OU researchers to carry out the continental-scale image data analysis."

The spatial-temporal dynamics and trends of year-long water bodies in the CONUS during 1984 to 2016 were quantified by states and watersheds. During that period, 10 water-poor states in the southwest and northwest United States had statistically significant decreasing trends in surface water area, but 20 water-rich states in the southeast United States and the northern Great Plains had statistically significant increasing trends. Climate was the primary driving factor for such diverse trends in year-long surface water area since 1984.

"According to climate predictions, annual precipitation is likely to decrease in the Southwest but increase in the eastern United States during the 21st century, therefore, the observed diverse trends of surface water body areas since 1984 could continue to occur in the future," said Xiao.

OU researchers combined the surface water area data with the land water storage data from NASA's Gravity Recovery and Climate Experiment during 2002 to 2016 to investigate the data dynamics in severe drought and pluvial years. The detailed analyses in California and the Southern Great Plains (Kansas, Oklahoma and Texas) clearly highlight a large withdrawal of groundwater in those drought years and slow post-drought recovery of surface water area, groundwater and land water storage over years.

A paper on this study by Xiao and his team, "Divergent Trends of Open Surface Water Body Area in the Contiguous United States During 1984 to 2016," has been published by the Proceedings of the National Academy of Sciences of the United States of America. The manuscript, tracking number of 17-19275, can be found online in PNAS Latest Articles.

Credit: 
University of Oklahoma

Let them eat xylose: Yeast engineered to grow efficiently on novel nutrients

image: Saccharomyces cerevisiae is a popular organism for industrial applications for its ethanol and thermo-tolerance, and well studied genetics.

Image: 
Mogana Das Murtey and Patchamuthu Ramasamy (CC BY-SA 3.0)

MEDFORD/SOMERVILLE, Mass. (March 26, 2018) -- Researchers at Tufts University have created a genetically modified yeast that can more efficiently consume a novel nutrient, xylose, enabling the yeast to grow faster and to higher cell densities, raising the prospect of a significantly faster path toward the design of new synthetic organisms for industrial applications, according to a study published today in Nature Communications.

In synthetic biology, organisms such as bacteria or yeast may be transformed into "mini-factories" when fed nutrients to produce a wide range of products, from pharmaceuticals to industrial chemicals and biofuels. However, a central challenge has been the efficient conversion of abundant feedstocks into the final product, particularly when the feedstock is not something the bacteria or yeast normally "eat."

In this study, the researchers noted that conventional approaches to modifying organisms to consume novel nutrients constitutively (i.e. with no "off switch") can lead to inefficiencies when the nutrient metabolic pathways are not linked to downstream pathways for stress-responses, cell growth and other functions important for the health of the organism.

Taking a different approach, the researchers took a set of regulatory genes, called a GAL regulon, that normally processes galactose - a favorite on the yeast menu of nutrients - and replaced some of the genes with those that become activated by, and direct the breakdown of, xylose. All other genes in the GAL regulon were unchanged. In doing so, they preserved a more natural interaction between the genes that govern feeding and those that govern survival. The new synthetic regulon, dubbed XYL, enabled the yeast cells to grow more rapidly and to higher cell densities.

"Instead of building a metabolic framework from the ground up, we can reverse engineer existing regulons to enable an organism to thrive on a novel nutrient," said Nikhil U. Nair, Ph.D., assistant professor of chemical and biological engineering at Tufts and corresponding author of this study. "Adapting native regulons can be a significantly faster path toward the design of new synthetic organisms for industrial applications."

One such application is the production of ethanol as a biofuel. Concerns have been raised that diverting significant portions of crops, such as corn, to biofuel production could have a negative impact on availability and cost of the food supply. However, xylose is a sugar derived from the otherwise indigestible parts of plant material. The ability to ferment xylose can be a path to biofuel production that does not compete with the food supply.

As part of the study, Nair and his team took a closer look at what exactly accounted for the improved survival of the xylose-eating yeast organism. They found numerous genes activated in the XYL regulon-controlled yeast that upregulated pathways involved in growth, such as cell wall maintenance, cell division, mitochondrial biogenesis and adenosine triphosphate (ATP) production. Yeast strains that had constitutive (mostly unregulated) control of xylose metabolism triggered pathways related to cell stress, starvation and DNA damage.

"Our study applied this approach to xylose, but it suggests a broader principle - adapting native regulons for the efficient assimilation of other non-native sugars and nutrients," said Nair. "Nature has already done the work of tuning genes and metabolic pathways to the environment of the organism. Let's make use of that when introducing something new on the menu."

Credit: 
Tufts University

Oxycodone use shifts in Australia after tamper-resistant versions introduced

After the introduction of tamper-resistant oxycodone in Australia, dispensing rates for higher-strength formulations decreased for people younger than 65 years, but there was no change in older adults, according to new research in CMAJ (Canadian Medical Association Journal).

Canada, the United States and Australia are the highest per capita consumers of opioids worldwide. Opioid use has increased 15-fold in Australia over 20 years (1992 to 2012), making it the country with the second highest per capita consumption of oxycodone. In 2014, the country introduced tamper-resistant controlled-release oxycodone.

The study looked at whether reformulation changed use of controlled-release oxycodone and opioid-related harms in a sample cohort of 36 528 adults who had at least one filled prescription for oxycodone during the study period (July 2012 to November 2016). After reformulation, dispensing of oxycodone in both 10-30 mg and 40-80 mg strengths gradually decreased for people under age 65 years, for total decreases of 11% and 31.5%, respectively. People younger than 65 years, especially those younger than 45 years, were more likely to switch to morphine after reformulation, and there was an increase in participants of all ages switching to oxycodone/naloxone.

"The observed decline in dispensing of higher-strength oxycodone controlled-release in participants less than 65 years of age may be due to an increase in switching to other strong opioids, chiefly morphine, rather than an increase in ending use," writes Dr. Andrea Schaffer, University of New South Wales, Sydney, Australia, with coauthors. "This is of concern because it suggests that people may be seeking out opioids without tamper-resistant properties."

The authors note that as the study was observational, the results do not indicate causation between reformulation and changes in behaviour, but rather an association.

Despite reductions in dispensing of stronger oxycodone, poisonings from injected oxycodone did not decrease, as measured by calls to the New South Wales Poison Information Centre, which receives about 50% of all poisoning calls yearly in Australia.

"We did not find an increase in ending use of strong opioids in parallel with an increase in switching to other non-tamper-resistant strong opioids," write the authors.

They note that people under age 65 who were using higher-strength opioids and switched to different types of opioids had been identified as having a higher risk of opioid use problems and should be closely monitored by their physicians.

Credit: 
Canadian Medical Association Journal

E-cigarette aerosol exposure causes craniofacial abnormalities in mice

Alexandria, VA, USA - At the 47th Annual Meeting of the American Association for Dental Research (AADR), held in conjunction with the 42nd Annual Meeting of the Canadian Association for Dental Research (CADR), Suraj Kandalam, Virginia Commonwealth University, Richmond, presented a poster titled "E-cigarette Aerosol Exposure Causes Craniofacial Abnormalities in Mice." The AADR/CADR Annual Meeting is in Fort Lauderdale, Fla., USA from March 21-24, 2018.

E-cigarettes are battery powered nicotine delivery systems that vaporize e-liquids, a solution primarily composed of propylene glycol (PG), glycerol or vegetable glycol (VG), nicotine, flavorant and colorants. While cigarettes are known to affect craniofacial structures in utero, causing diverse congenital abnormalities, little is known about the effects of e-cigs on craniofacial development. This study aimed to determine the effects of e-cig aerosol mixtures (e-cigAM) on shape changes of craniofacial structures in developing murine embryos in vivo.

E-cigAM was produced by bubbling 10 puffs of e-cig aerosol into PBS using a custom made pump device. E-cigAMs were generated for four e-liquids -- research grade and nut flavor with nicotine and research grade and nut flavor without nicotine. Osmotic pumps loaded with e-cigAM were implanted into 10 week-old female mice, which were mated seven days later.

Embryos were harvested and imaged on a high resolution micro-CT scanner. The images were reconstructed and 3D constructs were created. Craniofacial landmarks were analyzed using geometric morphometric analysis and compared to embryos from PBS-treated controls.

"In vivo exposure to e-cigAM during pregnancy decreased embryo number," said Suraj Kandalam." E-cigAM exposure also generated shape changes including narrowing and shortening of the orofacial area in RG and flavored e-cigAMs. "Significant differences in distance between the mandible and premaxilla and of the occipital bone in both research grade with and without nicotine were observed compared to control. The nut flavor with nicotine showed significant differences in all orofacial aspects as compared to control, including length of zygoma, premaxilla, malar process and mandible."

Flavored e-cigAM showed greater detrimental effects than RG in all treatment. The addition of nicotine in flavored groups enhanced these effects. The results indicate that fetal exposure to e-cigAM alters craniofacial development.

Credit: 
International Association for Dental, Oral, and Craniofacial Research

Custom sequences for polymers using visible light

image: This is a custom sequence of different compositions in a single polymer chain, created by simply exposing an ongoing polymerization reaction to different on/off sequences of visible light.

Image: 
Akiko Inagaki

Tokyo, Japan - Researchers from Tokyo Metropolitan University used a light-sensitive iridium-palladium catalyst to make "sequential" polymers, using visible light to change how different building blocks are combined into polymer chains. By simply switching the light on or off, they were able to realize different compositions along the polymer chain, allowing precision control over physical properties and material function. This may drastically simplify existing polymer production methods, and help overcome fundamental limits in creating new polymers.

The world is full of long, chain-like molecules known as polymers. Famous examples of "sequential" copolymers, i.e. polymers made of multiple building blocks (or "monomers") arranged in a specific order, include DNA, RNA and proteins; their specific structure imparts the vast range of molecular functionality that underpins biological activity. However, making sequential polymers from scratch is a tricky business. We can design special monomers that assemble in different ways, but the complex syntheses that are required limit their availability, scope and functionality.

To overcome these limits, a team led by Associate Professor Akiko Inagaki from the Department of Chemistry, Tokyo Metropolitan University, applied a light-sensitive catalyst containing iridium and palladium. By switching a light on and off, they were able to control the speed at which two different monomers, styrene and vinyl ether, become part of a polymer chain. When exposed to light, the styrene monomer was found to be incorporated into the copolymer structure much more rapidly than in the dark, resulting in a single copolymer chain with different compositions along its length. Parts that are rich in styrene are more rigid than those rich in vinyl ether; by using different on/off light sequences, they could create polymers with a range of physical properties e.g. different "glass transition" temperatures, above which the polymer becomes softer.

The newly developed process is significantly simpler than existing methods. The team also found that both types of monomer were built into the polymer via a mechanism known as "non-radical coordination-insertion"; this is a generic mechanism, meaning that this new method might be applied to make polymers using a wide range of catalysts and monomers, with the potential to overcome the limited availability of monomer candidates.

Credit: 
Tokyo Metropolitan University

'Wiggling and jiggling': Study explains how organisms evolve to live at different temperatures

image: An enzyme's dance during the biological reaction it promotes determines at which temperature the enzyme works best.

Image: 
Dr Marc van der Kamp and Michael Connolly

The brilliant physicist Richard Feynman famously said that, in principle, biology can be explained by understanding the wiggling and jiggling of atoms. For the first time, new research from the University of Bristol, UK and the University of Waikoto, New Zealand explains how this 'wiggling and jiggling' of the atoms in enzymes - the proteins that make biological reactions happen - is 'choreographed' to make them work at a particular temperature. Enzyme catalysis is essential to life, and this research sheds light on how enzymes have evolved and adapted, enabling organisms to evolve to live at different temperatures.

This is the first study to link the enzyme's dance (in atomic detail) directly to its optimal temperature. These findings provide new insights into how the structure of enzymes is related to its role as a catalyst and importantly, could provide a route to designing better biocatalysts for use in chemical reactions in industrial processes, such as the production of drugs. It also hints at why proteins were eventually preferred by evolution over nucleic acids as catalysts in biology: proteins offer much more ability to 'tune' their 'jiggling and wiggling' and their response to chemical reactions.

Dr Marc van der Kamp and Professor Adrian Mulholland (Bristol) worked with Professor Vic Arcus (Waikoto, NZ) and colleagues, to find how the 'wiggling and jiggling', or the dynamics of enzymes is 'tuned down' during the reaction they catalyse. As a result, the heat capacity of enzymes* changes during the reaction, and it is the size of this change that is the critical factor in determining the temperature at which the enzyme works best.

So what causes the heat capacity of an enzyme to change during the reaction? And how is this different in different enzymes, so that their catalytic activities are tuned to suit the organism and the temperature of the environment they live in?

Dr Van der Kamp said: "Our computer simulations of the 'wiggling and jiggling' of enzymes at different stages in the reaction tells us how these structural fluctuations give rise to the difference in heat capacity, and thereby can predict the optimum temperature of an enzyme. Our work demonstrated that we can do this accurately for two completely different enzymes, by comparing to experimental data.

"What is fascinating to see is that the whole enzyme structure is important: the 'dance' does not only change close to where the chemical reaction takes place, but also in parts much further away. This has consequences for evolution: the combination of the enzyme structure and the reaction the enzyme catalyses will define its optimal working temperature. A subtle change in structure can change the 'dance'."

The work helps explain how organisms can evolve to live at different temperatures, and hints at why proteins were eventually preferred by evolution over nucleic acids as catalysts in biology: proteins offer much more ability to 'tune' their 'jiggling and wiggling' and their response to chemical reactions.

Enzymes have an optimum temperature at which they are most catalytically active. Above that temperature, they become less active. The textbook explanation is that enzymes unfold (lose their functional shape), but this is not correct. Instead, a basic physical property - the heat capacity - explains and predicts the temperature dependence of enzymes. The heat capacity changes during the reaction and is 'tuned' to give the optimal temperature.

Credit: 
University of Bristol

Two genes likely play key role in extreme nausea and vomiting during pregnancy

image: A new study led by Marlena Fejzo at UCLA has identified two genes associated with hyperemesis gravidarum, a condition that causes extreme nausea and vomitting during pregnancy.

Image: 
UCLA Health

Most women experience some morning sickness during pregnancy, but about 2 percent of pregnant women experience a more severe form of nausea and vomiting.

Sometimes the symptoms are so serious that hospitalization is required. Known as hyperemesis gravidarum, the condition is the same one that Kate Middleton, the Duchess of Cambridge, endured in her pregnancies.

A new study led by researchers at UCLA and published in the journal Nature Communications has identified two genes associated with hyperemesis gravidarum, whose cause has not been determined in previous studies. The genes, known as GDF15 and IGFBP7, are both involved in the development of the placenta and play important roles in early pregnancy and appetite regulation.

"It has long been assumed that the pregnancy hormones, human chorionic gonadotropin or estrogen, were the likely culprits of extreme nausea and vomiting, but our study found no evidence to support this," Marlena Fejzo, the study's first author, said. She is an associate researcher at the David Geffen School of Medicine at UCLA. The two genes, she added, coincidentally are linked to cachexia, a weight loss and muscle wasting condition that leads to death in about 20 percent of cancer patients and has similar symptoms to hyperemesis gravidarum.

Fejzo herself had hyperemesis gravidarum and lost a pregnancy to the condition in 1999. The debilitating symptoms can include rapid weight loss, malnutrition and dehydration due to persistent nausea and/or vomiting.

Current medications to treat the condition are largely ineffective and can lead to serious health consequences for both mother and baby. The condition is the second leading cause of hospitalization during pregnancy. Women often require intravenous fluids and, in the most severe cases, feeding tubes.

Previous research has shown that severe nausea and vomiting during pregnancy often runs in families, suggesting that genetics plays a role. For this study, the team compared the variation in DNA from pregnant women with no nausea and vomiting to those with hyperemesis gravidarum to see what the differences were between the two groups. DNA variation around the genes GDF15 and IGFBP7 was associated with hyperemesis gravidarum. The findings were then confirmed in an independent study of women with hyperemesis gravidarum.

In a separate follow-up study, researchers then proved the proteins GDF15 and IGFBP7 are abnormally high in women with hyperemesis gravidarum. They presented these findings at the International Colloquium on Hyperemesis Gravidarum in 2017.

The next step is to determine whether GDF15 and IGFBP7 protein levels can be altered safely in pregnancy to minimize nausea and vomiting.

The findings help to suggest a new avenue of research into a condition for which treatments have progressed little in the past.

"It is my hope that one day a medication that affects this pathway will be used to successfully treat and possibly cure hyperemesis gravidarum," Fejzo said.

Credit: 
University of California - Los Angeles Health Sciences

Study IDs important role for specific gene in 16p11.2 deletion autism

image: Green staining shows the MVP protein expressed in neurons.

Image: 
Picower Institute for Learning and Memory

In a new study of one of the most common genetic causes of autism, neuroscientists at MIT's Picower Institute for Learning and Memory have identified a specific molecular mechanism that appears to undermine the ability of neurons in affected mice to properly incorporate changes driven by experience. The findings published in the Journal of Neuroscience therefore suggest that a particular gene, MVP, is likely consequential in people with 16p11.2 deletion syndrome.

Accounting for up to 1 percent of autism cases, 16p11.2 deletion occurs in people who are missing a small region of DNA near the center of one copy of chromosome 16. For years, scientists have been working to determine exactly how the reduced presence of 29 protein-encoding genes leads to clinical symptoms of the syndrome such as autism-like behaviors, developmental delay and intellectual disability.

"This has been a major problem for the field," said senior author Mriganka Sur, Newton Professor of Neuroscience in the Picower Institute and director of the Simons Center for the Social Brain at MIT. "People have looked at the entire region in mice. Our strategy was different. We thought, can we make a hypothesis about a critical gene that should play an important role?"

The team led by postdoctoral associate Jacque Pak Kan Ip focused on MVP, which is known for encoding a protein that shuttles RNAs and proteins from the nucleus to the rest of cells - a generally vital function. It is particularly important in the immune system and is known to regulate other genes that are as well. Though MVP is also known to be among the 29 affected in people with 16p11.2 deletion syndrome, its specific function in neurons has barely been investigated. To change that, the researchers devised a series of tests of MVP in a well-understood region in the visual cortex, where the brain processes sight from both eyes.

Keeping an eye open for change

Ip and co-authors employed the time-honored protocol of "monocular deprivation," or temporarily shutting one eye for a week. Normally, responses in visual cortex neurons related to the closed eye become weaker, but responses related to the remaining open eye become stronger, as if to compensate for the change in ability. This neural circuit adjustment to experience is called "homeostatic plasticity."

In the normal mice, closing an eye for a week had the expected effect. But in mice with one copy of MVP missing, the researchers observed a telling difference. Responses related to the closed eye still weakened, but responses from the open eye did not get stronger. Homeostatic plasticity was disrupted.

"After seeing that MVP is responsible, we asked how MVP does it," Ip said.

In those further tests, the team found that neurons in MVP-reduced mice experienced less electrical current across their excitatory synapse connections with other neurons, suggesting reduced functional excitatory synapses. They found other differences, too. MVP-reduced mice overexpressed the gene STAT1, an immune-system gene known to be regulated by MVP.

In 2014 Sur's lab had found that mice without STAT1 have unusually strong open-eye responses after monocular deprivation. Now in the new study, with less MVP than usual and too much STAT1, mice experienced the opposite. Sure enough, when the researchers knocked down STAT1 as well as MVP, they were able to bring back a near-normal open-eye response to monocular deprivation, suggesting that loss of MVP disrupts homeostatic plasticity by allowing for an overabundance of STAT1.

Then Ip, Sur and co-authors dug even deeper. They found that in MVP-reduced mice, neurons weren't producing the expected open-eye responses because they weren't expressing a key receptor, the GluA1 AMPA receptor, on the surface of dendritic spines.

Even though the findings were made, by design, in the visual cortex, the authors said they expect the disruption of homeostatic plasticity to occur elsewhere as well.

"This gene's presence is reduced everywhere in the brain," Sur noted.

Relationship with immune system

In addition to illustrating how a specific gene may contribute to the symptoms of 16p11.2 deletion syndrome, Sur said, the findings also raise an intriguing, broader question about the central nervous system: Is it perhaps not a coincidence that some of its ability to adjust to and incorporate experience comes from genes that are also active in the immune system?

"The immune system is really a system of learning and memory," Sur said. "You get infected and the body makes antibodies and the next time there is a 'memory' of the infection. It is conceptually a very similar idea."

Credit: 
Picower Institute at MIT

Race, pre-pregnancy BMI may help predict maternal weight gain

CHICAGO--Race and pre-pregnancy body mass index (BMI) both affect leptin and adiponectin levels, and leptin levels in mid-pregnancy may be an important predictor of weight gain during pregnancy, new research suggests. The results will be presented on in a poster on Sunday, March 18 at ENDO 2018, the 100th annual meeting of the Endocrine Society in Chicago, Ill.

"Gaining too much or too little weight during pregnancy poses potential health risks. Leptin and adiponectin, hormones released primarily from fat cells, are known to play roles in appetite regulation, insulin resistance, lipid metabolism, blood pressure and the development of metabolic syndrome. During pregnancy, lower levels of adiponectin are associated with higher risk of gestational diabetes and higher leptin levels are observed in women who develop pre-eclampsia," said lead study author Adam Jara, D.O., Ph.D., a clinical instructor at Ohio State University in Columbus, Ohio.

Jara and his co-authors at Ohio State investigated the effects of race and pre-pregnancy BMI on serum adiponectin, leptin, the leptin-to-adiponectin ratio (LAR) throughout pregnancy and postpartum, and their effects on weight gain during pregnancy.

The research team recruited 80 pregnant women--38 African-American and 42 Caucasian women--from the Ohio State University Medical Center Prenatal Clinic. The authors measured adiponectin and leptin levels 3 times during pregnancy--early, middle and late--and again after delivery.

Both race and pre-pregnancy BMI appeared to affect adiponectin and leptin levels during pregnancy and after birth.

After controlling for race and pre-pregnancy BMI, serum levels of adiponectin, leptin and the LAR during pregnancy predicted total maternal weight gain. Leptin levels in mid-pregnancy were the most predictive of weight gain during pregnancy.

Among African-American women with obesity, the LAR increased significantly from early to mid-pregnancy, stayed high in late pregnancy and decreased after birth. By contrast, among Caucasian women with obesity, the LAR did not change significantly over time.

Overall, adiponectin levels decreased from early to late pregnancy, with an increasing trend after birth. Higher pre-pregnancy BMI was associated with lower levels of adiponectin. African-American women had lower serum adiponectin at each time point they were tested, compared to Caucasian women with equivalent pre-pregnancy BMIs.

Overall, serum leptin increased throughout pregnancy and declined after birth. Lower leptin levels were associated with lower pre-pregnancy BMIs.

The National Institute of Nursing Research (NINR), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Center for Advancing Translational Sciences (NCATS), and an Ohio University Transition to Research Independence Award supported the study.

Credit: 
The Endocrine Society

Signaling pathways to the nucleus

image: The hormone auxin controls many processes in plants.

Image: 
Source: Institute of Biology II/University of Freiburg

A team of researchers from the University of Freiburg have discovered how the plant hormone auxin is transported within the cell and how this signaling pathway helps to control gene expression in the nucleus. Auxin regulates many processes in plants: from embryonic development, to the development of organs, all the way to responses to changes in the environment. The team recently published its research in the journal Cell Reports.

According to current scientific models, auxin works with other proteins to fulfill its function. When auxin content in the nucleus rises, receptors bind in the presence of auxin repressors, initiate repressor degradation and enable auxin responsive transcription factors to trigger gene expression. Because it is believed that auxin content in the nucleus is important for this, the researchers focused on how auxin gets into the nucleus and how this process is controlled. The researchers from the University of Freiburg therefore collaborated with colleagues from Munich and Okayama, Japan, to test new, fluorescent, auxin-mimicking molecules in single cells. These molecules allowed them to visualize the accumulation of auxin in the cell without triggering any auxin-related processes. They were thus able to demonstrate that the auxin-mimicking molecules accumulated primarily in the endoplasmic reticulum (ER), which is a system of flat tubules that is a continuation of the nuclear membrane directly connected to the nucleus.

Next, the team studied how the ER, nucleus, and other cell parts work together to absorb auxin in the nucleus. Because there are currently no adequate methods of directly measuring the transport of auxin between the cell's different compartments, the researchers developed a combined experimental-theoretical approach that allows them to use a combination of microscopy, quantitative data analysis, and mathematical modeling to observe how individual plant cells react to different auxin levels. Based on the results of their research, they concluded that the flow of auxin from the ER to the nucleus represents an important signaling pathway within the cell to regulate auxin levels in the nucleus, and hence in supporting processes triggered by auxin.

Credit: 
University of Freiburg

False beliefs about MMR vaccine found to influence acceptance of Zika vaccine

People's willingness to use a Zika vaccine when it's available will be influenced by how they weigh the risks associated with the disease and the vaccine, but also by their misconceptions about other vaccines, a new study has found.

While a Zika vaccine is in development, the study by researchers at the Annenberg Public Policy Center (APPC) of the University of Pennsylvania examined factors that will affect the eventual acceptance or rejection of such a vaccine.

The study, published in the Journal of Public Health, found that people's erroneous beliefs about an association between the measles, mumps, and rubella (MMR) vaccine and autism were a predictor of people's lessened intention to get a Zika vaccine. The study also found that people's perceptions of the severity of the Zika virus as well as their general belief in the power of science to solve problems increased their intention to get the vaccine.

"When a new disease arises, people who lack understanding of the new threat may extrapolate from their knowledge of other diseases," said Yotam Ophir, a Ph.D. candidate at Penn's Annenberg School for Communication who co-authored the study with APPC Director Kathleen Hall Jamieson. "We found that the misbelief about the MMR vaccine's association with autism was more influential on the decision of whether to get vaccinated for Zika than even perceptions of Zika itself, which is worrisome, especially in light of the persistence of that misinformation."

The study analyzes 2016 data from APPC's Annenberg Science Knowledge (ASK) survey gathered during the outbreak of the Zika virus, which is mosquito-borne and can be sexually transmitted. When a pregnant woman is infected, the virus can cause an increased risk of birth defects, including microcephaly. The study includes survey responses from 3,337 individuals between August 25, 2016 and September 26, 2016, which was part of a larger, 34-week survey of U.S. adults on attitudes, behavior, and understanding of the Zika virus.

Key findings of the study include these:

The more likely someone is to believe in the false association between the use of the MMR vaccine and autism, the less likely that person is to use a Zika vaccine;

People who believe in the ability of science to overcome problems were more likely to intend to use a Zika vaccine;

People who believe that Zika causes the birth defect microcephaly (which is accurate) and those who believe Zika is likely to cause death (which is inaccurate) were more likely to intend to vaccinate;

People who were engaged in behaviors to protect against Zika were less likely to intend to get the vaccination - which "may be the result of their confidence that their actions pre-empt the need to be vaccinated," the researchers said.

The researchers said the study has practical and theoretical implications. Once the Zika vaccine exists, health communicators will have to cope with "vaccine hesitancy" and anti-vaccine communications. The research also adds evidence to the need for health communicators "to address a spill-over effect from misbeliefs about one vaccine on intention to use another."

The bogus association between the MMR vaccine and autism has been disproven in numerous studies. However, the argument is still prominent among people who oppose vaccinations. "Scientists often look at the effect of misinformed beliefs about the MMR vaccine on people's intention to vaccinate children with the triple vaccine, but they don't as often look at the dangerous spillover effects that these misbeliefs can have," said Ophir, who will be joining APPC as a postdoctoral fellow.

He said that prior research has shown that it is very hard to completely debunk misinformation, such as the mistaken belief that the MMR vaccine causes autism, but the study results suggest that accurately communicating about the risks of Zika can help lessen the detrimental effects of the misbelief. "Even if we can't change what people think about the MMR vaccine, if we can give them an accurate picture of how vulnerable they are to a disease such as Zika, they can make a more informed decision about it," Ophir said.

The study was funded by the Science of Science Communication endowment of the Annenberg Public Policy Center of the University of Pennsylvania.

Credit: 
Annenberg Public Policy Center of the University of Pennsylvania