Culture

Blue holes bring forgotten chemical element back on stage

image: The origin of the pnictogen catalysis: The large empty space, the "blue hole," on antimony, inside the molecule. Example: molecular model of Sb(C6F5)3, empty space in the molecule in blue. Sb = antimony.

Image: 
© UNIGE

About a third of all Swiss exports result from fundamental discoveries in synthetic chemistry. Certain drugs and perfumes, as well as food and agricultural products -- and even Ferrari's famous red colour - are derived from new molecular structures invented by Swiss scientists. Chemists at the University of Geneva (UNIGE), Switzerland, have just discovered that chemical bonds based on antimony -- a forgotten element at the very bottom of the periodic table -- yield powerful new catalysts that can be used to accurately stimulate the transformation of a molecule from within. These bonds complement existing interactions such as conventional hydrogen bonds or the more recent chalcogen bonds with sulfur. This finding, published in the journal Angewandte Chemie, will lead to the creation of innovative materials that will become part of our daily lives. It has triggered a small revolution in the world of synthetic chemistry, which had always believed that there was a limit to the number of possible bonds to build new catalysts.

Basic research in chemistry requires creativity. But the chemist, a true sculptor of molecular structures, needs specific tools. To induce a molecular transformation, the molecule that the scientist wants to alter -- the substrate -- must enter into contact with an element from the periodic table in the catalyst. Under normal conditions, the contact -- or bond -- used is with hydrogen. But the creative possibilities are reduced when restricted to this single element. Finding new ways to initiate contact between molecules would make it possible to transform them differently, thereby enabling chemists to create new materials. "That's why my team is constantly looking for new bonds for catalysis," explains Stefan Matile, a professor in the Department of Organic Chemistry in UNIGE's Faculty of Science. "After discovering the sulfur-based bond for catalysis, called the chalcogen, two years ago, we decided to look at another category in the periodic table, pnictogen elements, which are distinguished by their metallic components." Nitrogen, phosphorus, arsenic, antimony and bismuth all belong to this category.

Elements revealed using empty space

Unearthing new bonds for the catalysis requires innovation. "Research usually focuses on studying the electrons of the elements. We took the opposite approach: we only examined the empty spaces left by the electrons, which are essential for molecular construction, so we could look for possible new interactions", continues professor Matile. And rightly so, since heavy pnictogen elements, like ripe fruits, are more flexible and deformable than, for instance, hydrogen, which is very compact. In this way, the empty spaces become more accessible and intelligible for the chemists.

Seven elements were chosen by the UNIGE scientists. "Theoretical calculations make for a better visualisation of the empty spaces," says Amalia I. Poblador-Bahamonde, a researcher in the Organic Chemistry Department in the Faculty of Science. "That's why we first carried out computer modeling of the seven elements alone so we could visualise where both the electrons and the empty spaces were located. We then did it again with the molecules to be tested in order to measure the strength of the new bond." The more visible the molecule's empty spaces became, the better the bond works, and the element is a better catalyst. At this theoretical stage, antimony turned out to be the best of the seven elements tested. The findings encouraged the chemists to focus on elements at the bottom of the periodic table, an area that is little explored in organic chemistry.

An element that has been ignored since ancient Egypt

Basing their work on the theoretical modeling, the chemists studied the bonds using nuclear magnetic resonance, which makes it possible to visualise the molecules and the transformations in their structure. "Our results were perfectly consistent with the theoretical predictions," points out Sebastian Benz, a PhD student in professor Matile's team. "Antimony proved to be ultra-efficient once more, up to 4,000 times faster than the other elements tested in creating a new structure!"

Antimony turned out to be a surprise for the UNIGE researchers. It was used as eye makeup in ancient Egypt before falling into oblivion. This research puts the element firmly back into the spotlight, all thanks to the exceptional qualities it showed for molecular transformation. "Antimony is not only ultra-fast but also - unlike other catalysts that act on the molecule's surface - it works from within. This impacts on the material's entire environment and enables the chemist to be more precise when undertaking the transformations," continues professor Matile.

The pnictogen bonds with antimony are the third bonds for catalysis discovered by the UNIGE chemists, following anion-π bonds and chalcogen bonds with sulfur. All three introduce new ways of looking at molecular transformations and open up untried prospects. "We don't intend to stop there, of course: we're going to keep on looking for new bonds and ways in which we can make use of them!" says professor Matile. Illustrative examples for these bright perspectives are the first enzymes that work with anion-π bonds, made in the National Centre of Competence in Research (NCCR) Molecular Systems Engineering, and the first fluorescent probes that can visualise mechanical forces in living cells thanks to chalcogen bonds with sulfur, made in the NCCR Chemical Biology at UNIGE.

Credit: 
Université de Genève

Drinking sugary drinks may be associated with greater risk of death

NEW ORLEANS, March 21, 2018 -- Adults over the age of 45 who consume large amounts of sugary beverages including soft drinks, fruit drinks and fruit juices may have a higher risk of dying from heart disease or other causes, compared to those who drink fewer sugary drinks, according to preliminary research presented at the American Heart Association's Epidemiology and Prevention | Lifestyle and Cardiometabolic Health Scientific Sessions 2018, a premier global exchange of the latest advances in population based cardiovascular science for researchers and clinicians.

The researchers found a graded association between consuming more sugary beverages and an increased risk of death from heart disease or any cause. Study participants in the top 25 percent of consumers, those who tended to drink 24 ounces or more of sugary beverages each day, had twice the risk of death from coronary heart disease compared to those in the lowest 25 percent of people who drank less than 1 ounce. In addition, there was an increased risk of death from all causes, including other cardiovascular conditions. The study, however, found no link between the consumption of sugary foods and increased risk of death, a distinction the researchers said may be related to how sugary drinks and foods are processed by the body.

Several studies have shown an association between added sugar and obesity and various chronic diseases. However, few have been able to look at the association between increased sugar consumption and death. It is important to note that this study does not prove cause and effect, rather it identifies a trend.

"There were two parts of this question we wanted to understand," said Jean Welsh, Ph.D., M.P.H., study author, assistant professor at Emory University and a research director with Children's Healthcare of Atlanta. "Do added sugars increase risk of death from heart disease or other causes, and, if so, is there a difference in risk between sugar-sweetened beverages and sugary foods? We believe this study adds strong data to what already exists highlighting the importance of minimizing sugary beverages in our diet."

This study used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a U.S.-based longitudinal study of 30,183 black and white adults over age 45. The final study population was 17,930 after excluding those with a self-reported history of heart disease, as well as stroke and Type 2 diabetes. This type of study is designed to find an association or trend, not to prove cause and effect.

The researchers estimated sugary food and beverage consumption using a food frequency questionnaire. Sugar-sweetened beverages included those pre-sweetened, such as sodas and fruit drinks. Sugar-sweetened foods included desserts, candy and sweetened breakfast foods as well as foods to which calorie-containing sweeteners such as sugars or syrups had been added.

The participants were followed for an average of about 6 years, and researchers used death records to look at the cause of death, focusing on deaths from heart disease, such as heart attack, heart failure and deaths from all other causes.

The researchers observed this effect when they statistically made the participants equal with respect to income, race, education, smoking history and physical activity. When they controlled for known heart disease risk factors such as total calorie consumption, high blood pressure, abnormalities in blood lipids or body weight, the effect remained. Researchers did not see any increased risk with consumption of sugary foods.

The quantity and frequency of consumption of sugary beverages, coupled with the fact that they contain few, if any other nutrients, results in a flood of sugars that need to be metabolized, Welsh said. When people consume sugars in foods there are often other nutrients such as fats or proteins which slow down metabolism and may explain the different effect seen between the two.

The study's finding should encourage healthcare providers to ask patients about sugary beverage consumption during well visits to open the door to a conversation about a dietary change that could be made to reduce risk, Welsh said.

"We know that if healthcare providers don't ask patients about lifestyle practices linked to obesity and chronic disease, patients tend to think they're not important," Welsh said. "Simply asking patients about their sugary beverage consumption is valuable."

Credit: 
American Heart Association

Hunting squid slowed by rising carbon levels

image: This is a close up of adult bigfin reef squid, Sepioteuthis lessoniana.

Image: 
Blake Spady, Coral CoE

Scientists have found that high carbon dioxide levels cause squid to bungle attacks on their prey.

PhD candidate Blake Spady from the ARC Centre of Excellence for Coral Reef Studies (Coral CoE) at James Cook University (JCU) led the investigation. He said that the oceans absorb more than one-quarter of all the excess carbon dioxide (CO2) released into the atmosphere by humans and this uptake of additional CO2 causes seawater to become more acidic.

"Climate models project that unless there is a serious commitment to reducing emissions, CO2 levels will continue increasing this century to reach levels that will have far-reaching effects on sea life," he said.

Mr Spady said the team chose to study cephalopods (a group that includes squid, cuttlefish and octopuses) because while most previous behavioural studies have focused on fishes, the effects of elevated CO2 on highly active invertebrates is largely unknown.

"Cephalopods also prey on just about anything they can wrap their arms around and are themselves preyed upon by a wide range of predator species, so they occupy an important place within marine food webs."

The scientists tested the effects of elevated CO2 on the hunting behaviours of pygmy squid and bigfin reef squid.

"For pygmy squid, there was a 20% decrease in the proportion of squid that attacked their prey after exposure to elevated CO2 levels. They were also slower to attack, attacked from further away, and often chose more conspicuous body pattern displays at elevated CO2 conditions.

Bigfin reef squid showed no difference in the proportion of individuals that attacked prey, but, like the pygmy squid, they were slower to attack and used different body patterns more often."

Mr Spady said both species showed increased activity at elevated CO2 conditions when they weren't hunting, which suggests that they could also be adversely altering their 'energy budgets'.

"Overall, we found similar behavioural effects of elevated v on two separate cephalopod orders that occupy largely distinct niches. This means a variety of cephalopods may be adversely affected by rising CO2 in the oceans, and that could have significant consequences in marine ecosystems," said co-author Dr Sue-Ann Watson.

"However, because squid have short lifespans, large populations, and a high rate of population increase, they may have the potential to adapt to rapid changes in the physical environment," Mr Spady added.

"The fast lifestyle of squid could mean they are more likely to adapt to future ocean conditions than some other marine species, and this is the next question we intend to investigate."

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ARC Centre of Excellence for Coral Reef Studies

Three-dimensional printing and bioprinting for tissue engineering

Alexandria, VA, USA - 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), featured a symposium titled "Three-dimensional Printing and Bioprinting for Tissue Engineering." The AADR/CADR Annual Meeting is in Fort Lauderdale, Fla., USA from March 21-24, 2018.

Dental, oral and craniofacial tissues are complex structures requiring simultaneous regeneration of various tissues. This, in turn, causes major limitations in relation to conventional regenerative procedures.

3-D printing technologies have been introduced into both clinical dentistry and dental/craniofacial research with claims to eliminate these limitations. This symposium aims to review current developments and challenges in research related to 3-D printing and bioprinting technologies for regeneration of dental, craniofacial and oral structures.

The symposium featured the topics "Guided Self-assembly and Coding of Three-dimensional Living Architectures" by Utkan Demirci, Stanford University School of Medicine, Palo Alto, Calif., "3D-printing Constructs for Treatment of Critically-Sized Oral and Craniofacial Defects" by Lobat Tayebi, Marquette University School of Dentistry, Milwaukee, Wis., "Geometric Controls of Periodontal Tissue Regeneration Using 3-D Printing Technology" by Chan Ho Park, Seoul National University Dental Research Institute, Republic of Korea and "3-D Printing Technology for Periodontal/Peri-implant Regeneration" by Sophia Pilipchuk, University of Michigan, Ann Arbor, Mich.

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International Association for Dental, Oral, and Craniofacial Research

The curse of zombie fossils

image: Zombie fossil? This is an artist's impression of an undead T. rex. The missing parts are the result of degradation of the body after death.

Image: 
Herschel Hoffmeyer

New research has revealed how the history of life can be distorted by the ways animals decompose and lose body parts as they decay - and the ways in which decayed bodies ultimately become fossilised.

In a new study published in the journal Palaeontology, a group of palaeontologists from the UK and Ireland, led by the University of Leicester, has followed a macabre, and nasally-challenging road to knowledge - watching carefully as animal carcasses decompose in order to better understand the process.

Like on-screen zombies in popular TV programmes such as The Walking Dead that gradually deteriorate through time, fossils preserve only incomplete remains of the living body.

A key part of palaeontological research involves reconstructing long-extinct creatures to understand what they were like when they were alive. This knowledge allows us to answer fundamental questions - how did they move and interact with their environment? How did they feed and reproduce? Which of today's organisms are they most like and most closely related to?

Understanding how much of a fossil is missing, and what has been changed by decay and fossilisation, helps to create a more accurate picture of ancient animals and ecosystems. This is particularly important for things lacking hard skeletons and shells - including crucial fossil evidence of early animal life on Earth.

"As soon as an organism dies, it starts to decay, and this process of decomposition inevitably involves changes in how features or body parts look: they may collapse, alter their shape or position; all too soon they liquefy and are eaten by bacteria until nothing remains," says Professor Sarah Gabbott from the University of Leicester's School of Geography, Geology and the Environment.

Professor Mark Purnell, lead author of the study adds: "The more a body deteriorates over time, the more body-parts are missing - rather like modern representations of zombies in Game of Thrones and The Walking Dead.

"One consequence of this decay is that palaeontologists have to work with incomplete fossils. Some of the features that are present don't look anything like they did when the animal was alive, and many features are missing completely. The trick is to be able to recognise partially-decomposed features, and where body parts have rotted away completely."

The approach used in the UK-Irish collaboration involves 'laboratory decay experiments': keeping careful records of every body part as it decays away.

The results of rotting a whole range of dead animals, from hagfish and lampreys (primitive eel-like creatures) to insects and various worms, show that carefully designed experiments provide unique insights into the processes of decomposition and fossilisation.

In the new paper they highlight the importance of understanding how a fossil is formed before trying to reconstruct it - how the processes of decay that lead to loss of body parts interact with the processes that cause them to become preserved and fossilised.

Dr Maria McNamara, collaborator in the study, adds: "If we understand this we are better able to avoid producing incomplete restorations of animals with crucial parts missing or decayed, and to recognize and be aware of the gaps in our knowledge,".

Credit: 
University of Leicester

Seizures may be detected through sound

A new Epilepsia study indicates that individuals without electroencephalogram (EEG) training can detect ongoing seizures in comatose patients through a novel method by which patients' brain waves are converted to sound.

The traditional approach to interpreting EEGs requires physicians with formal training to visually assess the waveforms. This approach may not be practical in critical settings where a trained EEG specialist is not readily available.

Although sonification of EEG cannot replace the traditional approaches to EEG interpretation, it provides a potential tool for quickly assessing patients with suspected subclinical seizures such as nonconvulsive status epilepticus.

"The majority of seizures in critically ill patients are non-convulsive and many comatose patients do not recover because their brains keep seizing. Kids with these silent seizures, if they survive, will leave the hospitals with major cognitive impairment," said the lead author, Dr. Josef Parvizi, Professor of Neurology and Neurological Sciences at Stanford University Medical Center. "If detected in time, however, these seizures can be treated quickly and patients can recover without major harm to their brain. So it is time to think about alternative methods by which everyone, including even medical students, can detect such seizures."

Credit: 
Wiley

Does menopausal hormone therapy maintain the brain?

MINNEAPOLIS - Taking menopausal hormone therapy soon after menopause to relieve symptoms may also benefit the brain, according to a study published in the March 21, 2018, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"We found that one form of menopausal hormone therapy taken soon after menopause may preserve brain structure in the portion of the brain responsible for memory and thinking skills," said study author Kejal Kantarci, MD, MS, of the Mayo Clinic in Rochester, Minn., and a member of the American Academy of Neurology. "It may also reduce the development of amyloid plaques that can build up and lead to memory loss."

For the study, researchers identified 75 healthy women with an average age of 53 who were between five months to three years past menopause. Of those, 20 women took conjugated equine estrogen in pill form, 22 received estradiol via skin patches and 33 received a placebo of either the pills or patches. In addition, the women taking active hormone were also given progesterone pills for the first 12 days each month. Placebo pills were given to those in the placebo group.

Study participants were given memory and thinking tests as well as MRI scans at the start of the study, at 18 months, at three years and at the end of four years of hormone treatment, and then again three years after therapy ended. Researchers measured overall brain volume and the accumulation of brain lesions and compared scores on thinking and memory tests. A total of 68 women also had positron emission tomography (PET) scans to detect plaques in the brain that are related to memory loss and Alzheimer's disease.

Researchers found that participants who took estradiol via skin patches maintained brain volume in the dorsolateral prefrontal cortex, an area of the brain that assists with memory, thinking, planning and reasoning, over the seven years of the study. Women who maintained volume in this area of the brain were also more likely to have a lower amount of the amyloid plaque deposits that are related to memory loss and Alzheimer's disease. This suggests that estradiol therapy may have long-term effects on the brain.

Researchers also found that for those taking estrogen pills, there were greater structural changes in the brain during therapy, but those changes stopped when participants stopped taking the pills.

Scores on thinking and memory tests were similar for women in the hormone therapy groups and those taking placebo.

"More research is needed to determine the biological reasons behind brain changes during menopausal hormone therapy," said Kantarci. "Future research is also need to better define just how the different hormonal products, pills versus skin patches, affect the brain."

A limitation of the study is that the women were all in good cardiovascular health, so the results may not be similar for those with heart problems, diabetes or other health issues. However, Kantarci noted that not including those with heart issues may have made it easier to observe the effects of hormone therapy on the brain, since there was no interference from contributing heart problems.

Credit: 
American Academy of Neurology

Surpassing critical blood pressure threshold could signal hypertension regardless of age

Boston, MA-- Hypertension, abnormally high blood pressure, is associated with an increased risk of heart attack and stroke. Many healthcare professionals still believe that incremental changes in blood pressure are normal, and expected, with aging. A new study by investigators at Brigham and Women's Hospital, published in the journal of JAMA Cardiology, found that a systolic (top) blood pressure that regularly exceeds 120-125 mmHg could signal impending hypertension, regardless of age. These results are in line with the recently updated American College of Cardiology and American Heart Association high blood pressure guidelines, which categorize high blood pressure as greater than 130/80 mmHg.

"There used to be a widespread belief that a gradual increase in blood pressure over time is part of normal aging," says Susan Cheng, MD, a cardiologist at BWH and senior author on the paper. "But, if you look at native communities, where people live without the lifestyle exposures usually seen in industrialized societies, this trend is hard to find. And so, we wondered if blood pressure is supposed to very gradually increase over time or instead remain stable. We also wanted to find out, for people in whom blood pressure does rise, is there a tipping point at which hypertension starts to develop. In other words, if hypertension does develop, when does the change start to happen, what does it look like, and how might we prevent it?"

In the study, researchers examined data from 1,252 participants from the Framingham Heart Study, which contains one of the few existing cohorts with standardized blood pressure (BP) measurements performed at frequent intervals (every two years) over an extended period of time (1948 to 2005). The team defined hypertension onset as a blood pressure over or equal to 140/90 mmHg. Participants were categorized based on the age at which their hypertension was diagnosed (age 40-49, 50-59, 60-69, 70-79 years, or no onset).

The research team found that, among the patients who developed hypertension, blood pressure trajectories leading up to the onset of hypertension appeared similar in pattern. In fact, their blood pressure levels were generally stable until they approached the range of ~120-125 mmHg, above which their blood pressure rose rapidly and into the range of hypertension. This finding was consistent whether the hypertension developed in middle or older age, suggesting that blood pressures above this level could represent a critical threshold of vascular remodeling occurring in the body. Interestingly, this blood pressure range is in line with recently published guidelines that lowered the definition of high systolic blood pressure to 130 mmHg.

"Although our findings suggest the potential importance of working to keep your top blood pressure number below 120 mmHg, they also offer a hope for healthy aging - our results demonstrated that some individuals are able to maintain a very normal range of blood pressure throughout life," says Niiranen Teemu, MD, first author and a research associate at Brigham and Women's Hospital.

The researchers found that many people in the study were able maintain a systolic blood pressure below 120-125 mmHg and, in effect, delay the uptick of blood pressure elevation until much later in life and, in some cases, avoid it altogether. This new way of understanding life course trends in blood pressure could affect clinical practice by motivating physicians to be more vigilant when encountering blood pressure at or approaching uptick levels. Further investigations are needed to unravel the sequence of changes in the body that occur before hypertension sets in and to determine the potential benefits of interventions in preventing progressive rises in blood pressure, at any age.

Credit: 
Brigham and Women's Hospital

How often do medical problems lead to bankruptcy?

CAMBRDIGE, MASS.--A team of researchers led by an MIT economist has found that medical expenses account for roughly 4 percent of bankruptcy filings among nonelderly adults in the U.S.

The scholars combined medical records and financial data for hundreds of thousands of people to pinpoint the percentage of bankruptcies caused by medical costs, thus giving new empirical precision to a topic of considerable policy importance.

The 4 percent figure is lower than some commonly cited estimates, but the new statistic comes with a twist: It is part of a larger research project that found multiple negative economic consequences of having medical problems, including a 20 percent drop in earnings and an 11 percent drop in employment for adults between ages 50 and 59 who had been hospitalized.

This combination of effects - fewer medically rooted bankruptcies but pervasive workplace troubles for people with health issues - underscores the need to understand the full range of financial challenges people face due to their medical needs, the researchers say.

"It doesn't mean there aren't really adverse economic consequences from adverse health," says MIT economist Amy Finkelstein, co-author of a new paper outlining the findings. "It just turns out they're not [strictly] about bankruptcy. They're much more about lost employment and earnings."

The article, "Myth and Measurement - The Case of Medical Bankruptcies," appears today in the New England Journal of Medicine. The co-authors are Finkelstein, who is the John and Jennie S. MacDonald Professor of Economics at MIT; Carlos Dobkin, a professor of economics at the University of California at Santa Cruz; Raymond Kluender, a PhD student in economics at MIT; and Matthew Notowidigdo, an associate professor of economics at Northwestern University.

The study's main source of data consists of hospitalization records from the years 2003-2007 and credit reports from 2002-2011, from the state of California, for people over age 25. The study included about 780,000 people with health insurance and roughly 150,000 people without health insurance. That information was available to the research team only under particular conditions that preserved the anonymity of the people being studied.

By examining cases where previously healthy people were hospitalized, then tracking the finances of those people in subsequent years, the researchers were able to study the issue in a way that delivers a solid link between cause and effect - namely, how often medical events themselves are the principal cause of changes in financial status.

Some of the previous research on the frequency of medically caused bankruptcies used survey data to produce estimates; one commonly cited figure is that 60 percent of bankruptcies have medical causes. However, those estimates used self-reported data about health issues, among those who filed for bankruptcy, without establishing that medical costs were the principal cause of those bankruptcies.

"The approach of the prior literature was just conceptually not right," Finkelstein says.

The current study found that poor health has a larger impact on the uninsured than the insured: For instance, as a related, recently published paper by the research team shows, four years after being admitted to the hospital, people with insurance owe $300 more in unpaid medical bills, on average, while people without insurance have an average increase of $6,000 in unpaid medical bills.

The researchers also found that medically caused bankruptcies are minimal among the elderly - those over age 64 - who are likely to have Medicare and who tend to be retired, thus not suffering the earnings reductions that ill people in the workforce experience.

"We suspect what's driving the [level of] bankruptcy we find is the fact that some people lose their job because of adverse health, and in turn that causes them to go bankrupt," Finkelstein says. "That's just not going to [apply to] the elderly, because they're not working, so they don't have the labor market risk from poor health."

To be sure, Finkelstein acknowledges, the current study has some aspects that may need additional scrutiny. By focusing on examples involving hospitalization, the researchers could be missing some cases in which accumulated medical costs of other kinds drive people to bankruptcy - including medical costs incurred by children, parents, or other relatives.

"We're not going to go to the mat over the idea that [the rate of medically caused bankruptcies] is always going to be 4 percent in every context and by every measurement," Finkelstein says. Still, she notes, the accurate figure is likely to be much lower than other recent estimates imply.

To Finkelstein, the findings also have a clear upshot for policymakers and legislators. Grasping the full breadth of the economic consequences of poor health might affect the priorities of lawmakers, directing them to seek solutions for the lost income that many people endure after a serious medical event.

"Focusing on bankruptcy might lead you to think about bankruptcy protection reform," Finkelstein says, "and while that may or may not be useful in its own right, if you're interested in the economic consequences of poor health, you're missing a main issue and potential policy responses - thinking about how we might want to structure sick pay and disability insurance."

Credit: 
Massachusetts Institute of Technology

Systems approaches to optimizing deep brain stimulation therapies in Parkinson's disease

Systems biologists, physicists, and engineers have intensively worked at computational tools to analyze, predict, and optimize the effects of Deep Brain Stimulation (DBS) to treat chronic neurological diseases. These efforts often have overlapping objectives and closely-related methods, but they are rarely compared, combined, or jointly discussed, perhaps because they often target different research communities.

A new WIREs Systems Biology and Medicine review systematically brings this information together to identify the major milestones in the development of systems approaches to the modeling and study of Parkinson's disease and DBS. These approaches acknowledge the interactive nature and interdependence of various factors to optimize the therapeutic effects of DBS in individual patients.

"Although effective and generally safe, DBS remains a fascinating puzzle to scientists, physicians, and engineers. The therapeutic mechanisms of DBS, in fact, are still elusive and the current, semi-permanent stimulation protocols have often motivated the investigation of ways to make DBS less invasive and more efficient," said lead author Dr. Sabato Santaniello, of the University of Connecticut. "In this review article, we show how different strides in medical imaging, computer modeling, and control strategies have paved the way towards a truly patient-specific optimization of DBS therapy.

Credit: 
Wiley

Mat baits, hooks and destroys pollutants in water

image: Specks of titanium dioxide adhere to polyvinyl fibers in a mat developed at the Rice University-led NEWT Center to capture and destroy pollutants from wastewater or drinking water. After the mat attracts and binds pollutants, the titanium dioxide photocatalyst releases reactive oxygen species that destroy them.

Image: 
Rice University/NEWT

HOUSTON - (March 21, 2018) - A polymer mat developed at Rice University has the ability to fish biologically harmful contaminants from water through a strategy known as "bait, hook and destroy."

Tests with wastewater showed the mat can efficiently remove targeted pollutants, in this case a pair of biologically harmful endocrine disruptors, using a fraction of the energy required by other technology. The technique can also be used to treat drinking water.

The mat was developed by scientists with the Rice-led Nanotechnology-Enabled Water Treatment (NEWT) Center. The research is available online in the American Chemical Society journal Environmental Science and Technology.

The mat depends on the ability of a common material, titanium dioxide, to capture pollutants and, upon exposure to light, degrade them through oxidation into harmless byproducts.

Titanium dioxide is already used in some wastewater treatment systems. It is usually turned into a slurry, combined with wastewater and exposed to ultraviolet light to destroy contaminants. The slurry must then be filtered from the water.

The NEWT mat simplifies the process. The mat is made of spun polyvinyl fibers. The researchers made it highly porous by adding small plastic beads that were later dissolved with chemicals. The pores offer plenty of surface area for titanium oxide particles to inhabit and await their prey.

The mat's hydrophobic (water-avoiding) fibers naturally attract hydrophobic contaminants like the endocrine disruptors used in the tests. Once bound to the mat, exposure to light activates the photocatalytic titanium dioxide, which produces reactive oxygen species (ROS) that destroy the contaminants.

Established by the National Science Foundation in 2015, NEWT is a national research center that aims to develop compact, mobile, off-grid water-treatment systems that can provide clean water to millions of people who lack it and make U.S. energy production more sustainable and cost-effective.

NEWT researchers said their mat can be cleaned and reused, scaled to any size, and its chemistry can be tuned for various pollutants.

"Current photocatalytic treatment suffers from two limitations," said Rice environmental engineer and NEWT Center Director Pedro Alvarez. "One is inefficiency because the oxidants produced are scavenged by things that are much more abundant than the target pollutant, so they don't destroy the pollutant.

"Second, it costs a lot of money to retain and separate slurry photocatalysts and prevent them from leaking into the treated water," he said. "In some cases, the energy cost of filtering that slurry is more than what's needed to power the UV lights.

"We solved both limitations by immobilizing the catalyst to make it very easy to reuse and retain," Alvarez said. "We don't allow it to leach out of the mat and impact the water."

Alvarez said the porous polymer mat plays an important role because it attracts the target pollutants. "That's the bait and hook," he said. "Then the photocatalyst destroys the pollutant by producing hydroxyl radicals."

"The nanoscale pores are introduced by dissolving a sacrificial polymer on the electrospun fibers," lead author and former Rice postdoctoral researcher Chang-Gu Lee said. "The pores enhance the contaminants' access to titanium dioxide."

The experiments showed dramatic energy reduction compared to wastewater treatment using slurry.

"Not only do we destroy the pollutants faster, but we also significantly decrease our electrical energy per order of reaction," Alvarez said. "This is a measure of how much energy you need to remove one order of magnitude of the pollutant, how many kilowatt hours you need to remove 90 percent or 99 percent or 99.9 percent.

"We show that for the slurry, as you move from treating distilled water to wastewater treatment plant effluent, the amount of energy required increases 11-fold. But when you do this with our immobilized bait-and-hook photocatalyst, the comparable increase is only two-fold. It's a significant savings."

The mat also would allow treatment plants to perform pollutant removal and destruction in two discrete steps, which isn't possible with the slurry, Alvarez said. "It can be desirable to do that if the water is murky and light penetration is a challenge. You can fish out the contaminants adsorbed by the mat and transfer it to another reactor with clearer water. There, you can destroy the pollutants, clean out the mat and then return it so it can fish for more."

Tuning the mat would involve changing its hydrophobic or hydrophilic properties to match target pollutants. "That way you could treat more water with a smaller reactor that is more selective, and therefore miniaturize these reactors and reduce their carbon footprints," he said. "It's an opportunity not only to reduce energy requirements, but also space requirements for photocatalytic water treatment."

Alvarez said collaboration by NEWT's research partners helped the project come together in a matter of months. "NEWT allowed us to do something that separately would have been very difficult to accomplish in this short amount of time," he said.

"I think the mat will significantly enhance the menu from which we select solutions to our water purification challenges," Alvarez said.

Credit: 
Rice University

Fixing soybean's need for nitrogen

image: A soybean root with nodules, These nodules house bacteria that "fix," or extract, nitrogen from the atmosphere for the plant's use.

Image: 
Luiz G. Moretti.

Soybean is rich in protein, which is great for the humans and animals eating it. But this high protein content comes at a cost.

To make protein, soybean plants need a lot of nitrogen. The plants get some of the nitrogen they need by working with specialized bacteria in the soil. These bacteria live in root nodules. They pull nitrogen from the atmosphere and convert it to a form the plants can use.

But this process-biological nitrogen fixation-may not provide all the nitrogen soybean crops need. Farmers may have to apply nitrogen fertilizer as well.

A new study, however, shows it's possible to increase the number of soybean root nodules--and the bacteria that live there--to increase crop yields. This could remove the need to apply additional nitrogen fertilizers.

"That opens the possibility of achieving higher yields of soybean based exclusively on biological fixation," says Mariangela Hungria, a researcher at Embrapa Soja, Brazil.

Hungria, lead author of the study, and her colleagues coated soybean seeds with the bacteria (the usual method used by growers). They supplied additional bacteria by spraying it on the plants during other stages of growth. Soybean plants that received the additional spray inoculation developed more root nodules. And more nodules led to higher yields.

In fact, adding bacteria to seeds increased yields by 27% and 28%. Spraying bacteria on the soy fields during growth pushed up yields even further.

The increase in root nodules after additional spray inoculation surprised Hungria and her colleagues. Previous research indicated that each nodule makes it more difficult for soybean plants to develop subsequent ones. But in this study, soybean plants were able to form new nodules when researchers provided more bacteria.

"To discover that nodules aren't regulated as strictly as previously thought is an important finding," says Hungria. "The limitation happens particularly at the beginning of soybean growth when the first nodules appear." After that initial stage, more nodule growth is possible.

More biological nitrogen fixation, and less nitrogen through fertilizer, can also increase sustainability. First, it reduces carbon emissions. Nitrogen fertilizers are usually produced using fossil fuels. "For every pound of nitrogen fertilizer manufactured, at least 10 pounds of carbon dioxide may be released," Hungria states.

The second improvement in sustainability is on the field. Excess nitrogen fertilizers from the field can flow into bodies of water. Too much in an aquatic ecosystem can cause algal blooms. These deplete the water of oxygen and lead to "dead zones" devoid of life. Biological fixation using bacteria, however, means more of the nitrogen is used by the crop.

Less fertilizer use also has an economic impact. Nitrogen fertilizer costs can add up quickly, both for farmers and for countries. Brazil imports about 70% of the nitrogen fertilizers used in the country.

Several farms in Brazil began using the study's strategy in October 2016 (the summer crop in Brazil). Initial results have been promising, says Hungria. The higher soybean yields seen in the study are sustained on these larger scales.

Hungria thinks these results will extend beyond Brazil as well. "But they have to be verified because the genetic background of soybean is different in each country," she says. Collaborations with Kansas State University, to verify if the results can be extended to the U.S., have just started.

Researching bacteria and nitrogen fixation may just be the beginning. "I think microorganisms can be the 'stars' of a new era of agriculture, in which we consider not only food security but also sustainability," she says.

Credit: 
American Society of Agronomy

Researchers explore enzymetic activities based on nanocomplex sensors

image: This is the Nano journal cover.

Image: 
World Scientific

A team of researchers from Ludong University compared the susceptibility of different triangle silver nanoprisms (TSNPRs) towards H2O2 and elucidated the influence of capping agents and structural size on the etching process, with the aim of optimizing TSNPRs for H2O2 etching-based biosensors, such as glucose and glucose oxidase. The result of their research was recently published in a paper in NANO.

As a characteristic two-dimensional plasmonic nanostructure, triangular silver nanoprisms (TSNPRs) possess an extreme degree of anisotropy since their lateral dimension is larger than the thickness, giving highly sensitive surface plasmon resonance (SPR) responses. Many strategies have been developed for the biosensors based on target analytes induced morphologies changes and plasmonic peak shifts. A typical approach is to etch TSNPRs by an oxidative hydrogen peroxide, also known as catalytic product of glucose oxidase (GOx). Relative TSNPRs etching-based plasmonic biosensors have been used for detecting glucose, antigen and DNA. However, synthesis of TSNPRs with well-defined tips needs the assistance of appropriate capping ligands, such as citrate, polyvinylpyrrolidone (PVP) and so on. To date, there has not been a systematic study on the influences of the capping agents on H2O2 etching of TSNPRs. Besides, the analysis of structural size could also provide valuable information since size parameter is essential for the efficacy and performance of TSNPRs for sensing and detection.

The team of researchers from the School of Life Sciences at Ludong University performed a study to compare the susceptibility of different TSNPRs towards H2O2 and elucidated the influence of capping agents and structural size on the etching process, aiming to optimize TSNPRs for glucose oxidase etching-based biosensor. Detail analysis revealed that the small sized TSNPRs capping with citrate alone have been expected to be of great interest in the trace of glucose and glucose oxidase. This research work appears in the latest issue of the journal NANO.

This work performs systematic studies on nanoprisms for glucose oxidase etching-based biosensor. Nanoprisms with a small size and citrate capping were served as a substitute for big nanoprisms to sense glucose, offering a number of advantages such as high sensitivity, improved calibration, time-saving and extend detection ranges. and These sensing assays have been expected to be of great interest in the trace of glucose, providing an ultrahigh sensitive glucose etching-based analytical platform for point-of-care diagnostics of diabetics.

Credit: 
World Scientific

In drawing tests, US children draw female scientists more today than in previous decades

The participation of women in science has risen significantly in the United States since the 1960s. A new meta-analysis reviewed five decades of "Draw a Scientist" tests to determine whether children's drawings have mirrored that change. The study found that U.S. children and adolescents today draw female scientists more often than in earlier decades, but overall, female scientists are still depicted much less frequently than males in children's and youths' drawings.

The study, conducted by researchers at Northwestern University, appears in the journal Child Development, a publication of the Society for Research in Child Development.

In the 1960s and 1970s, less than 1% of U.S. children's drawings depicted a female scientist. In the 1980s and later, that percentage had risen to 28. "These findings shed light on how children learn to associate science with men and how they respond to changes in their cultural environment such as increases in women's representation in science," says David I. Miller, Ph.D. candidate in psychology at Northwestern University, who led the study.

The researchers used literature databases such as Google Scholar to identify 78 studies of U.S. "Draw a Scientist" tests over the last 50 years. The studies included more than 20,000 children in kindergarten through 12th grade. While the first study included in the analysis collected data from 1966 to 1977, all of the other studies collected data from 1985 to 2016.

In conducting their meta-analysis of U.S. children's gender-science stereotypes linking science with men, the researchers hypothesized that these stereotypes would weaken over time as women's representation in science grew stronger and media increasingly depicted females as scientists. They found that children depicted female scientists more often in later decades.

The study also found that children did not draw significantly more male than female scientists until ages 7-8; in kindergarten, they drew approximately equal percentages of male and female scientists. During elementary and middle school, the tendency to draw male scientists increased rapidly with children's age. These developmental differences suggest a growing awareness of gender differences and greater exposure to male than female science role models in school and mass media.

"Given these results, girls today may develop interests in science more freely than before because children's stereotypes of scientists have become less masculine over time," explains Alice H. Eagly, professor of psychology at Northwestern University, who coauthored the study. "But because stereotypes remain, teachers and parents should present children with multiple examples of female as well as male scientists across many contexts such as in science courses, on television shows, and in informal conversations."

Credit: 
Society for Research in Child Development

Specific gene region in hypertension revealed

image: Renin-angiotensin.

Image: 
University of Tsukuba

Tsukuba, Japan - Genes encode proteins and proteins dictate cell function. Therefore, the thousands of genes expressed in a cell determine what that cell can do. Among the multiple elements that are involved in the precise regulation of gene expression are enhancers, which are short region of DNA that can be bound by proteins (activators) to increase the likelihood of transcription of a particular gene.

One notable regulatory cascade that involves enhancers is the renin-angiotensin system (RAS) that plays a major role in blood pressure regulation and electrolyte homeostasis. Because increased expression of the protein renin leads to a rise in blood pressure, its transcription must be finely regulated.

While upregulation of the gene renin in the promoter and enhancer elements is relatively well established, the mechanisms controlling its feedback transcriptional suppression are poorly understood. This knowledge gap prompted a team of researchers from the University of Tsukuba to delve deeper into understanding this important regulatory cascade.

"We deleted either 5? or 3? regions of the endogenous mouse renin (mRen) in mice, and placed the animals in a hypertensive environment. While the mRen gene bearing the 3? deletion was appropriately downregulated, the one bearing the 5? deletion (-5E) lost hypertension responsiveness," explains Aki Ushiki, lead author of the study, which was recently reported in Molecular and Cellular Biology. "This means the -5E region is essential for the basal expression of the mRen gene."

Based on their findings, they proposed the -5E element functions as an enhancer under normal conditions and is involved in full activation of mRen gene transcription. Conversely, in the hypertensive state, the enhancer activity somehow becomes attenuated by the hormone angiotensin signaling, which leads to suppression of mRen gene transcription.

"Understanding of this enhancer-mediated transcriptional modulatory mechanism for mRen gene has a broad impact on not only the RAS field but also enhancer biology in general," corresponding author Keiji Tanimoto says. "Also, as the mRen enhancer core sequence is fairly conserved in humans, our findings shed light on the unexplored distal regulatory region of renin genes and provide a novel mechanistic insight into renin gene regulation."

Credit: 
University of Tsukuba