Culture

Antibiotics from the sea

image: Divers collect leaves of Posidonia oceanica in the bay of Calvi (Corsica). On this plant many planctomycetes have been found.

Image: 
Christian Jogler

Nearly three-quarters of all clinically relevant antibiotics are natural substances, produced by bacteria. However, the antibiotics that are currently available are losing their effectiveness and increasing numbers of pathogens are becoming resistant. This means there is an urgent need for new antibiotics, but at present fewer than one per cent of known species of bacteria are available for the search for active substances. The remaining 99 per cent are considered ‚impossible to cultivate' and are therefore hardly studied.

In addition, the ability to produce antibiotics is not evenly distributed among bacteria. "Talented producers are primarily microorganisms with complex lifestyles, an unusual cell biology and large genomes," explains microbiologist Christian Jogler of Friedrich Schiller University, Jena. "Such organisms produce antibiotic compounds and deploy them in the fight against other bacteria for nutrients and habitats," he adds. Anywhere that such microbiological battles over resources take place and nutrients are scarce is a promising place to search for potential producers of antibiotics.

Targeted cultivation of potential antibiotics producers

That is exactly what Jogler and his team have done. With the help of diving robots and scientific divers, they looked for Planctomycetes in a total of 10 marine locations. "We know that Planctomycetes live in communities with other microorganisms and compete with them for habitat and nutrients," says Jogler, explaining what makes this group of bacteria of interest to the researchers.

With samples from the Mediterranean, the North Sea, the Baltic Sea and the Black Sea, as well as the Atlantic, the Pacific and the Arctic Ocean, the scientists succeeded in creating pure cultures of 79 new Planctomycetes. "These pure cultures together represent 31 new genera and 65 new species," adds lead author Dr Sandra Wiegand.

Unknown cell division and antibiotic potential

Bioinformatic and microscopic methods were used to characterise the newly obtained pure cultures. "The bioinformatic analysis was holistic in its approach," says Wiegand. The potential to produce small molecules such as antibiotics was studied, as were the processes of cellular signal transduction. The latter are a measure of the complexity of the microbial lifestyle and therefore a further pointer towards antibiotic production. "The results of these analyses show that the newly obtained Planctomycetes have extraordinarily complex lifestyles and have the potential to produce new antibiotics," she added.

The researchers were able to provide experimental confirmation of some of their bioinformatic analyses in this study. Among other things, they investigated the cell biology of the Planctomycetes that had been isolated. "They divide in a very different way from all other important pathogenic bacteria," says Jogler. Furthermore, the research shows unexpected new mechanisms of bacterial cell division. Above all, however, the study provides impressive evidence that supposedly ‚non-cultivable' bacteria can be obtained and characterised in pure culture.

According to the authors of the study, many aspects of their current work can be transferred to other potential antibiotic producers. "Hypothesis-driven cultivation and holistic characterisation are essential for discovering something really new and opening up new therapeutic avenues," stresses Jogler, who only moved to Jena a few weeks ago. The Professor for Microbial Interactions is pleased that he has found an ideal environment for his research at Friedrich Schiller University, with its Cluster of Excellence ‚Balance of the Microverse'.

Credit: 
Friedrich-Schiller-Universitaet Jena

Disparities in care, mortality among hospitalized homeless adults with cardiovascular conditions

What The Study Did: Disparities in hospital care as measured by procedure rates and in-hospital death rates between homeless and nonhomeless adults hospitalized for cardiovascular conditions in New York, Massachusetts and Florida were examined in this observational analysis.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Rishi K. Wadhera, M.D., M.P.P., M.Phil., of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, is the corresponding author.

(doi:10.1001/jamainternmed.2019.6010)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Media advisory: The full study is linked to this news release. This study is being released to coincide with presentation at the American Heart Association's Scientific Sessions 2019.

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JAMA Network

Heart pumps associated with complications in some patients after heart stent procedure

In critically ill patients who require a heart pump to support blood circulation as part of stent procedures, specific heart pumps have been associated with serious complications, according to a new study led by cardiologists at Washington University School of Medicine in St. Louis.

Though the observational study does not prove that the heart pumps -- ventricular assist devices -- are the cause of complications, it suggests that with current practice patterns, there is an association between the use of the pumps and an increased risk of bleeding, kidney problems, stroke and death in patients undergoing stent procedures. The study authors are calling for more research evaluating the heart pumps marketed under the brand name Impella.

Results from the study were presented Nov. 17 at the American Heart Association's Scientific Sessions 2019 in Philadelphia and published simultaneously in the journal Circulation.

After statistically adjusting for certain variables, the researchers found an increased risk of death, bleeding, acute kidney injury and stroke among patients while they were still hospitalized after receiving Impella pumps versus balloon pumps. In particular, the Impella pump was associated with a 24% higher risk of death than seen with balloon pumps and a 34% increased risk of stroke compared with the balloon pump. Both of these differences are statistically significant. In no category was the Impella pump associated with improved outcomes.

"These results deserve a closer look to try to better understand the link between the device and its complications," said lead author Amit P. Amin, MD, a Washington University cardiologist and associate professor of medicine, who is presenting the data. "They suggest that perhaps a more measured approach -- one that balances risks and benefits -- is needed in this critically ill population. These data are observational, so they can't prove causation. But they underscore the need for large, randomized clinical trials and prospective registries to better understand and guide the use of cardiac support devices."

The researchers analyzed data from the Premier Healthcare Database that included information from 48,000 patients treated at 432 U.S. hospitals. Each patient in the study underwent a heart stent procedure, which involves opening a blocked artery in the heart to improve blood flow. Some patients undergoing the stent procedure are seriously ill, often having other medical conditions including heart failure, low blood pressure, complex blockages and other cardiac problems that might lead doctors to decide to add a mechanical assist device during the procedure to help the heart pump a greater volume of blood. Of the patients in this study, just under 10% (4,782 patients) received an Impella heart pump. The remaining 90% (43,524 patients) received an intra-aortic balloon pump.

Most patients undergoing stent procedures don't need a ventricular assist device. This study is focused on the small segment (roughly 3% to 5%) of patients undergoing stent procedures for more advanced heart problems -- such as complex blockages or heart failure or cardiogenic shock, in which the heart loses its capacity to pump sufficient blood -- and need a ventricular assist device. Most patients receive an intra-aortic balloon pump, which rhythmically inflates and deflates in coordination with the heart's natural rhythm, to help push blood through the vessels. These pumps have been in use since the 1960s. But since 2008, a steadily increasing proportion of patients receive the more recently approved Impella pumps, which have small rotors that create a continuous flow of blood.

The data came from patients treated from 2004 to 2016. The Impella pump was introduced into clinical practice in 2008, allowing for comparisons from the time periods before and after this type of pump came into use. Impella use increased steadily from about 1% of patients receiving a pump in 2008 to almost 32% of all patients in 2016 undergoing stent procedures with support devices.

The researchers also found large variations in how often hospitals used Impella pumps. The hospitals that used Impella pumps more frequently had higher adverse outcomes, as well as higher costs associated with caring for these patients, despite controlling for clinical factors. The researchers analyzed the possibility that sicker patients were more likely to receive the Impella pump, perhaps explaining at least part of that association. Instead, they found a trend showing lower Impella use among more critically ill patients.

The authors caution that there are limitations to this observational study, such as physician preference for use of Impella or balloon pumps, or inability to account for factors that were not measured in the observational study. But since the majority of the data suggest no improvement in outcomes linked to the use of the Impella pump as well as serious complications, Amin and his colleagues call for more definitive research to better understand the appropriate role for circulatory support devices in clinical practice.

"These mechanical support devices are innovative and can efficiently pump blood to the body, but in this study, we found no association with improved outcomes with the Impella pumps," Amin said. "This warrants more study so we can understand which patients are likely to benefit from these cardiac assist devices and which are more likely to develop problems."

Credit: 
Washington University School of Medicine

Fertilization discovery could lead to new male contraceptive, help infertile couples

image: Claudia Rival, PhD, (from left) shares notes with Kodi Ravichandran, PhD, and Jeffrey J. Lysiak, PhD. The researchers have made a surprising discovery about fertilization and the egg's role in it, potentially paving the way for a new contraceptive.

Image: 
Dan Addison | UVA Communications

An unexpected discovery about fertilization from the University of Virginia School of Medicine reveals new insights on how sperm and egg fuse and could have major implications for couples battling infertility - and may lead to a future male contraceptive.

The finding has the potential both to boost the success rate of in-vitro fertilization and reduce its cost. "The infertility experts here at UVA are very excited about this," said researcher Jeffrey J. Lysiak, PhD. "This tells us a lot about fundamental biology, but we think it could also have important clinical applications."

The finding recasts the role of the egg in the fertilization process. The old notion of the egg as a passive partner for sperm entry is out. Instead, the researchers found, there are molecular players on the surface of the egg that bind with a corresponding substance on the sperm to facilitate the fusion of the two. "High school biology taught us a very sperm-centric version of fertilization," said UVA researcher Kodi Ravichandran, PhD. "And now it's very clear that it is a dynamic process where both the sperm and egg are equally and actively involved in the ultimate biological goal of achieving fertilization."

Not Dead Yet

Ravichandran and Lysiak's laboratories started collaborating few years back on how immature sperm go through developmental stages in the testes. During their studies, they noticed something unusual. Some immature sperm that appeared to be dying weren't dying at all - they were alive and healthy. These sperm had a molecular marker on their surface suggestive of a dying cell, and this marker grew stronger as the sperm matured. "This initially made no sense," Lysiak said. "We had to do a lot of experiments to show that, indeed, these were live, motile sperm."

It turned out that this marker on the sperm that often tells the body to remove dying cells is used differently and in an important way during fertilization. This marker, phosphatidylserine (PS), is normally held inside cells until they die, but it is also exposed, quite deliberately, on healthy, live sperm.

The egg, meanwhile, expresses protein partners that specifically and actively engage the PS on the sperm. This PS-based recognition, along with other interactions, promotes sperm-egg fusion. Masking the PS on the sperm, or preventing the receptors on egg from recognizing the sperm, block fertilization quite efficiently.

That has several intriguing implications. First, for couples struggling with infertility, doctors one day might try to enhance the exposure of PS on the sperm to promote the chance of conception. They also could examine a man's sperm before in-vitro fertilization to select sperm that are most likely to result in pregnancy. This could help prevent the need for multiple attempts and reduce the cost couples must bear.

"When men go in for infertility tests, they do a basic semen analysis, and the current analysis primarily looks at the number of sperm, can it swim and how does it look," Lysiak said. "It doesn't provide much of an idea of the sperm's fitness to fertilize." As part of this work, the Ravichandran and Lysiak groups have also designed a new test to determine the fertilization fitness of the sperm based on exposure of PS.

Second, the researchers believe that finding a way to mask phosphatidylserine on the sperm head could be a potential form of contraception. "It is a very likely possibility," Ravichandran said. "We blocked phosphatidylserine by three or four different ways [in lab dishes], and we are pleasantly surprised how well it blocks sperm-egg fusion."

Understanding Fertilization

Ravichandran, chairman of UVA's Department of Microbiology, Immunology and Cancer Biology, and Lysiak, of the Department of Urology, plan to explore the basic-science questions related to fertilization in their laboratories and the potential therapeutic applications through a company they have formed called PS-Fertility.

They noted that the exciting possibilities are very much a testament to the importance of fundamental scientific research into basic biological questions. "Fertilization has been studied for 100 years. One would think we would have figured out something as fundamental as fertilization," Ravichandran said. "But the answers is, although surprising, not really. There are still many black boxes we don't understand, and this opens up several new avenues to pursue."

Credit: 
University of Virginia Health System

Mantis shrimp vs. disco clams: Colorful sea creatures do more than dazzle

image: A peacock mantis shrimp guards its eggs.

Image: 
Lindsey Dougherty

When Lindsey Dougherty was an undergraduate student at CU Boulder in 2011, she got the chance to visit North Sulawesi, Indonesia, on a research trip. There, in the clear tropical waters off the coast, she encountered an animal that would change the course of her career.

It was the disco clam (Ctenoides ales). And it caught Dougherty's eye for good reason: Even in a coral reef, these tropical bivalves are explosions of color. They have bright-red appendages that dangle out of their shells and thin strips of tissue that pulse with sparkly light like a disco ball--hence their name.

In that moment, she found her research calling.

"How do they flash?'" Dougherty remembered thinking as she dove through the reef with scuba gear.

As a graduate student at the University of California, Berkeley, the young scientist solved that first puzzle: the clams, she discovered, carry tiny, silica spheres in their tissue.

Now back in Colorado as an instructor in the Department of Ecology and Evolutionary Biology (EBIO), Dougherty is pursuing an even trickier mystery: Why are these bivalves so colorful in the first place?

The answer could reveal new clues to how the interaction between species drives the evolution of ocean animals over millions of years.

It's a pursuit that has expanded to include several high school students and introduced Dougherty to an animal that may be even more groovy-looking than the disco clam--a fierce predator on the same coral reefs called the peacock mantis shrimp (Odontodactylus scyllarus).

And in a recently published paper in the journal Royal Society Open Science, she and her colleagues report that they may be finally getting close to solving that puzzle.

"It's a long time to spend on one organism," Dougherty said. "But I think it also shows how many questions there are about one seemingly simple clam."

Clams vs. mantis shrimp

To grasp Dougherty's obsession with this shelled organism, it helps to understand the weirdness of the disco clam.

Jingchun Li is a curator of invertebrates at the CU Museum of Natural History and advised Dougherty during her postdoctoral studies at CU Boulder. Li has spent her career exploring the diversity of the world's bivalves--a class of aquatic mollusks that include animals like clams, scallops and mussels.

"Normally, if you think about clams like the ones in clam chowder--they're little white things," said Li, also an assistant EBIO professor. "But these clams are so colorful. One hypothesis we had is this might be some sort of warning signal to predators saying, 'Don't eat me.'"

In other words, disco clams might taste really bad, and they advertise that to the world using their bright colors. Kind of like a coral reef version of poison dart frogs in the Amazon.

To test that idea, Li and Dougherty recruited several peacock mantis shrimp--which, despite their names, aren't actually shrimp--and kept them in tanks on the CU Boulder campus.

Like disco clams, these animals are pretty wild to look at. They come in a rainbow of colors, from blues and greens to neon orange and yellow. But don't let their appearance fool you. Known for their powerful punches, mantis shrimp can extend their front claws at speeds of nearly 75 miles per hour--fast enough to generate an underwater shock wave that can shatter aquarium glass on impact.

The researchers, in other words, set up an ecological contest between the colorful mantis shrimp and flashing clams.

They offered their mantis shrimp a choice between two types of disco clam tissue. The mantis shrimp could either eat bright-red meat from the clams' exterior or normal, white meat from their inner muscles.

The mantis shrimp didn't even hesitate. They went for the white meat.

"It turns out they really hate the red tissue," Li said.

That, along with chemical analyses of the two types of meat, certainly seemed to suggest that the team's poison dart frog hypothesis had been spot on.

But another wrinkle emerged: When the group offered the mantis shrimp white meat that was dyed to look red, the invertebrates still chowed down.

As Dougherty put it, "Whether or not the red color is a warning needs more research."

Vinegar vs. Sriracha

It's work that's happening now in Li's lab. She's hoping to discover whether the same mantis shrimp can learn to fear the color red--a key step in determining whether that shade may act as a warning signal.

Aiding Li in that effort are two seniors from Monarch High School in Louisville, Colorado, who are helping out in her lab through the Science Research Seminar program in the Boulder Valley School District. They're tackling a pretty basic question: What kinds of food taste gross to a mantis shrimp?

The students, Grateful Beckers and Elysse DeBarros, have spent their semester trying out different flavor combinations, which they add to chunks of supermarket shrimp meat. Once they find a suitably yucky taste, they'll mix it with meat dyed red to see if mantis shrimp will become wary of that hue over time.

Early results suggest that mantis shrimp can't stand the taste of vinegar but, like many people, don't seem to mind Sriracha sauce.

"They're so unique," Beckers said. "They're a large, interesting shrimp with a lot of interesting adaptations."

Dougherty herself may still have a way to go before she resolves the mystery that first caught her attention on the Indonesian reef all those years ago. But it's been a fascinating road of discovery for this Colorado native who first learned to scuba dive in the Pueblo Reservoir.

"I love the mountains, and I love diving. I don't think they should ever be mutually exclusive," Dougherty said. "Everyone is connected to the ocean whether they realize it or not."

Credit: 
University of Colorado at Boulder

Majority US parents cite socioeconomic factors negatively impact their families' health

WASHINGTON (November 18, 2019) - Nearly two-thirds of American parents of children under 18 (65%) report at least one economic, environmental, or lifestyle factor that limits their family's ability to live a healthy life, according to a new nationwide survey conducted by The Harris Poll on behalf of Nemours Children's Health System. Eighty percent of parents believe that they have sufficient resources to raise healthy children, but a majority also cite serious obstacles to staying healthy.

Sixty-eight percent of parents cite experiencing at least one of these factors in the past 12 months:

Being unable to pay one or more of their bills (32%)

Skipping a doctor/dentist appointment because they couldn't afford to pay for visits, or find transportation (32%)

Having trouble paying for or getting to a doctor/dentist appointment or medicine (30%)

Worrying about running out of food (23%)

Worrying about their/their family's personal safety (17%)

Trouble finding work or affordable child care (17% each)

Being unable to access a grocery store with healthy food options (10%).

And 65 percent say non-medical factors, like these, limit their family's ability to live a healthy life.

"Decades of research has shown that medical care is responsible for about 15 percent of health, but the other 85 percent is largely due to other factors such as education, food security, and safety," said R. Lawrence Moss, MD, FACS, FAAP, president and CEO of Nemours Children's Health System. "Our survey shows how shockingly normal it is for families to struggle to meet these needs that are crucial for children's health. By making smarter investments in the health of our nation's children, we can achieve massive returns, not only to a child's health, but of the next generation of adults."

The online survey of more than 1,000 U.S. parents of children under the age of 18, conducted for Nemours by the Harris Poll in October 2019, also found that more than half of parents (55%) report that a healthcare provider/insurer has not asked them about these issues, even though 69 percent of parents say they would like their healthcare provider to connect them with community resources. Only one-third (33%) say a healthcare provider/insurer asked them about these important non-medical factors in the past 12 months. Among those parents, most (68%) say they did receive a social service referral, but roughly one-third (33%) were unable to get help because of waiting lists (33%), an inability to pay for services (32%), a lack of transportation (27%), or similar challenges.

"Let's start by redefining 'health' and becoming the stewards of children's health that enable parents to get the support they need to help their children grow up healthy," added Moss. "Hospitals and health systems are well-positioned in the community to meet families' needs to stave off the long-term negative consequences these factors can have on a child's health, but only if we're able to realign financial incentives of health systems and build trusting partnerships with social service agencies, government, and commercial payers."

The survey also found most parents can be made better aware of how much chronic disease is influenced by socioeconomic factors compared to medical treatment. The vast majority (70 percent) mistakenly believe that prescription drugs have the biggest impact on preventing chronic conditions such as asthma and Type 2 diabetes.

These survey findings are part of a larger report, Redefining Health for the Well-Being of Children. Nemours released the report today to bring attention to the issue and provide vital resources for health care professionals and families.

Credit: 
Nemours

Researchers clear the path for 'designer' plants

Athens, Ga. - A team of researchers at the University of Georgia has found a way to identify gene regulatory elements that could help produce "designer" plants and lead to improvements in food crops at a critical time. They published their findings in two separate papers in Nature Plants.

With the world population projected to reach 9.1 billion by 2050, world food production will need to rise by 70% and food production in the developing world will need to double, according to estimates from the Food and Agricultural Organization of the United Nations. Improvements in crop plants could play a key role in that effort.

The team, led by Bob Schmitz, demonstrated an ability to identify cis-regulatory elements, or CREs, in 13 plant species, including maize, rice, green beans and barley.

Cis-regulatory elements are regions of noncoding DNA that regulate neighboring genes. If a gene and its CRE can be identified, they can be treated as a modular unit, sometimes called a biobrick. Targeting CREs for editing offers a more refined tool than editing genes, according to Schmitz, associate professor of genetics in the Franklin College of Arts and Sciences.

"Gene editing can be like a hammer. If you target the gene, you pretty much break it," he said. "Targeting CREs, which are involved in controlling gene expression--how a particular characteristic appears--allows you to turn gene expression up or down, similar to a dial. It gives us a tool to create a whole range of variation in expression of a gene."

Controlling a gene for leaf architecture, for example, might allow a plant breeder to choose the angle at which a leaf grows from a plant, which can play a significant role in the plant's light absorption and growth. Targeting the gene itself would provide two options: "on," where the leaf might grow at a 90-degree angle, and "off," where the leaf might grow straight down. But targeting the CRE instead of the gene would allow the grower to target a range of possibilities in between--a 10-degree angle, a 25-degree angle, a 45-degree angle, etc.

Once biobricks have been created and screened for the desired output, they could be used to produce "designer" plants that possess desirable characteristics--for example, salt-tolerant plants that can grow in a landscape with high salinity. The ability to design plants to grow in less-than-ideal landscapes will become more and more important as food growers strive to produce more in an environment facing increasing challenges, like drought and flooding.

Based on their success, the research team recently received a $3.5 million grant from the National Science Foundation to investigate the role of CREs in legumes, including peanuts and soybeans.

Underlying the grant proposal and the papers are technological breakthroughs developed by Zefu Lu, Bill Ricci and Lexiang Ji.

"Zefu took a high-throughput method for identifying specific elements that was developed for animal cells and found a way to apply it to plant cells. It took a long time to address the significant barrier of plant organellar genomes, but now we're able to do what the animal field has been doing for a few years," Schmitz said.

"When people try to find trait/disease associations, they look for mutations in genes, but the work in animals has shown that these non-gene regions also possess mutations that affect the way in which a gene is expressed. The regions we're identifying with this method are revealing regulatory information for gene expression control, which traditionally has been challenging to detect compared to genes."

One of Ricci's contributions was developing a technique that shows the link between CREs and the gene they control.

"Typically CREs are located right next to the gene they control, but in plants with larger genomes--soybeans, maize--it's become clear that these controlling elements can appear very far away," Schmitz said. "In two-dimensional space something may appear far away, over many thousands of base pairs, but Bill's method shows that in three dimensions, it's actually positioned right next to the gene."

This work--the first time it has been applied to plants--provided the foundation for the two papers published in Nature Plants, and Schmitz paid tribute to his team members' contributions.

"This is a group effort," he said. "Zefu, Bill and Lexiang were major drivers of this research."

"Widespread Long-range Cis-Regulatory Elements in the Maize Genome" provides genetic, epigenomic and functional molecular evidence supporting the widespread existence of long-distance loci that act as long-range CREs influencing if and how a gene in the maize genome is expressed.

In "The prevalence, evolution and chromatin signatures of plant regulatory elements," the researchers identified thousands of CREs and revealed that long-distance CREs are prevalent in plants, especially in species with large and complex genomes. Additional results suggest that CREs function with distinct chromatin pathways to regulate gene expression.

The team's work will be shared via publicly available epigenome browsers that were developed by Brigitte Hofmeister, a recent Ph.D. graduate from the Schmitz Lab.

"Our studies are genome wide, and we do a lot of technique and technology development, but it's not useful if people can't access it," Schmitz said. "We provide epigenome browsers that allow people studying leaf architecture, for example, to access information on the specific genes or traits they're interested in."

Industry is also interested in CREs, according to Schmitz. Their editing pipeline is well established for genes, and the next obvious target for editing is CREs once they are located.

"It's not just academia using this for basic science," he said. "The applications of this approach to identify CREs will become commonplace in industry to improve crop performance."

Credit: 
University of Georgia

Quantum light improves sensitivity of biological measurements

image: A multidisciplinary group of researchers has demonstrated that quantum light controlled can be used to make accurate measurements in real time without disrupting enzymatic activity.

Image: 
Simonetta Pieroni

WASHINGTON -- In a new study, researchers showed that quantum light can be used to track enzyme reactions in real time. The work brings together quantum physics and biology in an important step toward the development of quantum sensors for biomedical applications.

The complex molecules known as enzymes are responsible for many processes inside our bodies. However, they can be difficult to study with optical approaches because too much light will reduce their activity or even stop it altogether.

In The Optical Society (OSA) journal Optics Express, a multidisciplinary group of researchers showed that light controlled at the single-photon, or quantum, level can allow accurate measurements without disrupting enzymatic activity.

"Although it might be a few years before practical quantum sensors are achieved, this type of proof-of-principle experiment is important," said research team leader Ilaria Gianani from Università degli Studi Roma Tre in Italy. "It helps pinpoint the areas where we can start building shared knowledge with other fields and reveals where technological advancement is needed to make progress."

Single-photon control

When investigating biomolecules it is important to avoid using levels of light that might alter their properties or behavior. Achieving this can be challenging because low levels of light may not provide very much information and noise can easily overcome the faint signal. Today, enzymes are studied with measurements performed on assays collected from the main sample to avoid damaging the sample with light. This procedure not only takes time but also prevents direct observation of the enzymes in real time.

The researchers overcame this problem by developing a setup that allowed them to control the light extremely precisely -- at the level of a single photon. This made it possible to use low illumination without disrupting the enzymes, with the potential to achieve a better sensitivity. The capability to address the sample directly also allowed dynamic tracking with higher resolution.

"Key to our success was a collaboration between quantum physicists, who know how to deal with photons, and biologists, who know how to deal with biological systems." said Gianani. "Although it was difficult to exchange ideas at first, the team eventually grew together and developed a shared language that helped the work progress smoothly. This collaboration wouldn't have been possible without the supervision of Prof. M. Barbieri, principal investigator of the Quantum Optics Group."

Tracking enzyme activity

The researchers used their new technique to track changes in the chirality of a sucrose solution due to activity of an enzyme known as invertase. Tracking the chirality -- the ability of a given molecule to rotate the polarization of light -- provides information that can be used to determine how many molecules of sucrose have been processed by the enzymes. The experiments showed that quantum light can be used to probe enzyme activities in real time without perturbing the sample.

"This work is just one example of what quantum sensors could do," said Gianani. "Quantum sensors could be used to optimally use light for countless applications, including biological imaging, magnetic field sensing and even detection of gravitational waves."

The researchers say that there are some technological aspects to address before their approach could become a go-to method for tracking enzymatic reactions. For example, light losses are a strong limiting factor, but they hope their work will help spur technology development that could address this problem.

Credit: 
Optica

New 3D printing technique produces 'living' 4D materials

video: UNSW Sydney researchers have successfully merged 3D/4D printing with a chemical process to produce 'living' resin, which has huge potential for fields as diverse as recycling and biomedicine. This time-lapse video shows the printed 4D plastic material transforming over time. The research, led by Professor Cyrille Boyer, has been published in Angewandte Chemie International Edition.

Image: 
UNSW Sydney

Repairing and reusing plastics and delivering cancer drugs more effectively are only two of many of the potential applications a new 3D/4D printing technology might have, thanks to the pioneering work of a research collaboration between UNSW Sydney and The University of Auckland.

The researchers have revealed the successful merging of 3D/4D printing and photo-controlled/living polymerisation - a chemical process to create polymers - in a paper published in Angewandte Chemie International Edition on Friday.

4D printing is a subset of 3D printing where the printed object can transform its shape in response to certain conditions.

The new controlled polymerisation method, where the researchers used visible light to create an environmentally friendly "living" plastic or polymer, opens a new world of possibilities for the manufacture of advanced solid materials.

Polymers can be synthetic, such as plastic, as well as biological, for example, DNA.

The research built upon the UNSW Sydney Boyer Lab's 2014 discovery of PET-RAFT polymerisation (Photoinduced Electron/energy Transfer-Reversible Addition Fragmentation Chain Transfer polymerisation), a new way to make controlled polymers using visible light, using the Reversible Addition Fragmentation Chain Transfer (RAFT) polymerisation technique discovered by the CSIRO (Graeme Moad, San Thang and Enzo Rizzard).

Such polymers can be reactivated for further growth, unlike traditional polymers which are "dead" after being made.

Since this development, the technology has expanded and has proven useful for making well-controlled molecules for many applications, including drug delivery and other biomaterials.

World-first discovery

Lead author Cyrille Boyer said his team's latest breakthrough was a world first in the development of a new 3D printing system using PET-RAFT polymerisation, to allow 3D printed materials to be easily modified after printing.

"Controlled polymerisation has never been used in 3D and 4D printing before, because the rates of typical controlled polymerisation processes are too slow for 3D/4D printing, where the reaction must be fast for practical printing speeds," Prof Boyer said.

"After two years of research and hundreds of experiments, we developed a rapid process compatible with 3D printing.

"In contrast to conventional 3D printing, our new method of using visible light allows us to control the architecture of the polymers and tune the mechanical properties of the materials prepared by our process.

"This new process also gives us access to 4D printing and allows the material to be transformed or functionalised, which was not previously possible."

UNSW's Nathaniel Corrigan, co-first author with UNSW PhD candidate Zhiheng Zhang, said a bonus advantage of their new system was the ability to finely control all molecules in the 3D-printed material.

"4D printing is a subset of 3D printing. But with 4D printing, the 3D-printed object can change its shape and chemical or physical properties and adapt to its environment," Dr Corrigan said.

"In our work, the 3D-printed material could reversibly change its shape when it was exposed to water and then dried.

"For example, the 3D object starts as a flat plane and when exposed to certain conditions, it will start to fold - that's a 4D material. So, the fourth dimension is time."

From reducing waste to biomedical applications

The researchers are hopeful that their new 3D/4D printing process using PET-RAFT polymerisation will lead to the production of functional materials to solve many of the problems facing society today.

Prof Boyer said the new method had a multitude of applications for everyday items - particularly if a deformed or broken object needed to be repaired or modified.

"The main application is of course recycling, because instead of using a plastic object once, it can be repaired and reused," he said.

"For ordinary recycling you take the materials away and have to reconstruct them, but for the new 'living' material it will be able to repair itself.

"For example, if you want to put the UNSW logo on a mug, you can modify the surface of the object and grow the polymers to show UNSW because the object is not dead; it's a living object and can continue to grow and expand."

Dr Corrigan said another major benefit of the new process was its compatibility with biomedicine, because extreme conditions were unnecessary.

"Current 3D printing approaches are typically limited by the harsh conditions required, such as strong UV light and toxic chemicals, which limits their use in making biomaterials," he said.

"But with the application of PET-RAFT polymerisation to 3D printing, we can produce long polymer molecules using visible light rather than heat, which is the typical polymerisation method.

"Using heat above 40 degrees kills cells, but for visible light polymerisation we can use room temperature, so the viability of the cells is much higher."

Prof Boyer said objects made through this new process could more easily be used in advanced bio-applications, such as tissue engineering, for example, where a tissue structure is used to form new, viable tissue for medical purposes.

"Our new method targets small scale, niche applications in fields like microelectronics and biomedicine - a huge area for us - that require very advanced polymers," he said.

3D and 4D printing for everyone

Prof Boyer said their new technique would allow commercial and non-expert operators to produce materials with seemingly endless properties and applications.

"We want to explore our system to find and address any limitations to allow for better uptake and implementation of this technology," he said.

"There is so much we can do by combining 3D and 4D printing with controlled polymerisation to make advanced and functional materials for many applications to benefit society."

Credit: 
University of New South Wales

Uncovering the pathway to wine's acidity

image: Uncovering the pathway to wine's acidity

Image: 
Jill Wellington / Pixabay

University of Adelaide wine researchers say their latest discovery may one day lead to winemakers being able to manipulate the acidity of wines without the costly addition of tartaric acid.

The team of researchers has uncovered a key step in the synthesis of natural tartaric acid in wine grapes - identifying and determining the structure of an enzyme that helps make tartaric acid in the grapes.

"Tartaric acid is important in all wines - red, white and sparkling - providing the finished wine with the vital acid taste to balance the sweetness of alcohol," says project leader Associate Professor Chris Ford, Interim Head of the University of Adelaide's School of Agriculture, Food and Wine.

"For example, in white wines such as a dry Riesling from the Eden Valley, the liveliness of the wine on the palate and the delicate balance of fruit flavours is due to careful management of acid levels in the grapes and during winemaking.

"However, it is often the case that natural levels of acidity in grapes are not enough for winemakers' requirements, requiring the addition of more tartaric acid."

Estimates have suggested that this costs over $10 million to the Australian wine industry each vintage, so understanding what controls the natural levels of acids like tartaric in the grape berry has the potential to save the industry significant sums of money.

"For this to become a reality, we need first to understand the details of the biochemical pathway that produces tartaric acid in the grape," says Associate Professor Ford.

This recent discovery follows an earlier collaboration with University of California Davis, when in 2006 the first enzyme in the six-step pathway that leads from vitamin C (ascorbic acid) to tartaric acid was discovered. Now a second enzyme has been identified and its structure determined and results published in the Journal of Biological Chemistry.

Associate Professor Chris Ford and Dr John Bruning, a protein crystallographer and enzymologist from the School of Biological Sciences and Institute for Photonics and Advanced Sensing, worked with researchers at Flinders University, the James Hutton Institute, Dundee, and postgraduate students Crista Burbidge, Emi Schutz and Yong Jia. They identified the enzyme based on its similarity to a bacterial enzyme with the same properties.

The enzyme was confirmed on the basis of its biochemical activity, and crystals of the enzyme grown so that its structure could be determined to atomic resolution using high-powered X-rays.

"Now that we understanding the 3D structure of this enzyme we can define its function and therefore its chemical mechanism and how it carries out its job in the grape," says Dr Bruning.

"That means we can modify the structure for biotechnological purposes down the line, such as altering the protein to change tartaric acid levels in the plant, instead of directly adding the acid at huge cost to winemakers."

Associate Professor Ford says: "As each piece of this intriguing puzzle falls in to place, our understanding of the metabolism of this critical grape acid increases. We now need to get to grips with the genetic, environmental and viticultural factors we may be able to manipulate to modulate the natural levels of tartaric acid in the grape."

Credit: 
University of Adelaide

New finding on origin of avian predentary in Mesozoic birds

image: The pink arrow points to the predentary and the blue arrow points to the upper portion of the jaw, which has no teeth. Together, they may have been covered by a keratinous beak, and the predentary was most likely mobile

Image: 
IVPP

The predentary bone is one of the most enigmatic skeletal elements in avian evolution. Located at the tip of the lower jaw, this bone is absent in more primitive birds and in living birds; it is thought to have been lost during evolution. For over 30 years, the origin and function of the avian predentary has remained mysterious.

Now, however, Alida Bailleul, LI Zhiheng, Jingmai O'Connor and ZHOU Zhonghe from the Institute of Vertebrate Paleontology and Paleoanthropology (IVPP) of the Chinese Academy of Sciences have made significant progress towards solving this long-standing mystery. Their findings were published in Proceedings of the National Academy of Sciences of the United States of America (PNAS) on November 18.

Using a battery of analytical methods, the team, led by Dr. Bailleul, presents strong evidence that the avian predentary was covered by a keratinous beak - a horny sheath that covers the bones of the rostrum in all living birds, all of which are edentulous and have beaks. It also provides evidence the predentary was proprioceptive, i.e., it was able to detect external mechanical stimuli; and was mobile - thus representing a now extinct form of cranial kinesis.

Cranial kinesis occurs when joints are able to move within the skull - mainly between the upper jaw and the braincase. This feature is widespread in living birds; however, it is thought to be mostly absent in Mesozoic birds.

Based on her examination of the fossilized tissues of the predentary and other jaw elements of Yanornis martini from the Jehol Biota, Dr. Bailleul identified a specific type of cartilage inside the joint between the predentary and dentary that strongly suggests some movement between these elements.

The team noticed that the predentary is only found in ornithuromorphs that have teeth. However, the tip of the premaxilla - the bone of the upper bill that would have occluded with the predentary - is without teeth. This suggests that the tip of the upper jaw, like the predentary, was also covered with a keratinous beak.

The tiny beak at the tip of the skull, combined with the sensitive and mobile predentary bone and teeth that were most likely also proprioceptive, represents a unique feeding adaptation that allowed greater dexterity when manipulating food. Although bizarre and now extinct, this unique feeding apparatus persisted in the ornithuromorph clade for at least 58 million years, from the Early to the Late Cretaceous.

Using information from the fossilized tissues and preexisting data on the embryology of living birds, the team also formulated a hypothesis regarding the origin of this bone, suggesting it is a sesamoid, similar to the human knee cap. Identification as a sesamoid means this bone is a novel skeletal innovation unique to one lineage of ornithuromorphs, and that it did not arise from a preexisting skull bone.

Although additional research on fossils birds (and also extant birds) is required to confirm some of these hypotheses, the predentary is such a small bone that it is only rarely preserved, thus making it very difficult - if not impossible - to find specimens that can shed light on the remaining pieces of this mystery.

Credit: 
Chinese Academy of Sciences Headquarters

How religion can heighten or help with financial stress

Researcher contact:

Ashley LeBaron
Norton School of Family and Consumer Sciences
,801-404-8292
ash222@email.arizona.edu

Churchgoers who are strapped for cash may experience a spike in anxiety when the donation plate is passed. However, knowing they have a church family to support them in times of need may help ease their money worries.

A new study by University of Arizona researcher Ashley LeBaron illuminates the ways in which religious involvement can alleviate or exacerbate financial stress.

The study, published in the journal Psychology of Religion and Spirituality, draws upon 134 interviews with religious leaders and parents in Ireland and the United Kingdom who consider themselves to be "highly involved" in their religion.

The results suggest that religion's effects on financial stress are not black and white, said LeBaron, a doctoral student who studies family finance in the Norton School of Family and Consumer Sciences in the College of Agriculture and Life Sciences.

"There's an effort to view research on religion and family with a more balanced perspective - to acknowledge that in some ways, in some circumstances, religion can harm families, and in some circumstances, it can help families," LeBaron said. "That was a natural perspective to take with this paper because the data clearly showed that when families were talking about religion and how it impacted their finances, sometimes they talked about how religion was really beneficial to their finances and their family, and sometimes it made their financial stress worse."

The data was originally gathered for a different research project, not involving LeBaron, on religion's impact on families. Study participants were not specifically asked about their finances in the interviews. However, financial themes frequently emerged in their responses, which led a colleague at Brigham Young University to share the data with LeBaron for further analysis.

LeBaron and her co-authors, who include that colleague from BYU and two others, identified five ways in which religious involvement may relieve financial stress and four ways in which it may make financial stress worse.

How it can help

--Some of the study participants interviewed said that because religion reduced materialism and de-emphasized the importance of material objects, it made them less likely to be pressured to spend money to accumulate more things or "keep up with the Joneses."

--Some said they felt religion brought monetary blessings. They felt they were directly financially blessed because they donated money to the church, and they felt like their religious community was a source they could turn to if they needed financial support.

--More than half of those interviewed said religious giving brought them satisfaction and gave them a sense of purpose and meaning in their lives, which helped alleviate financial stress.

--Some said religion improved their perspectives on work. Even at times in which they didn't particularly enjoy their jobs, they said they were able to see their job is their calling and something bigger than themselves. Some also expressed a belief that God would provide for them as long as they worked hard, and that idea helped reduce financial stress.

--Religion fostered a positive outlook on financial struggles for many participants. In short, their belief in a higher power gave them hope that any financial challenges would ultimately turn out OK.

How it can hurt

--Some people reported feeling their religious involvement came with increased financial obligations and, as a result, increased financial stress. Some talked about the strain of making faith-based charitable donations or contributions to the church. Others talked about the financial cost associated with certain religion-driven lifestyle choices, such as not cohabitating before marriage, which means unmarried couples must pay for two residences instead of one. Some also talked about participating in financially demanding religious experiences, such as missions, pilgrimages or enrolling children in religious schools.

--Several interviewees talked about the fact that religion requires time sacrifice. They said commitments to church activities, such as volunteering or doing mission work, sometimes cut into their payable work hours.

--In about two-thirds of interviews, respondents said religious values clashed with their work. Some made career decisions based on their religious beliefs or family values. For example, one Catholic woman talked about giving up her job to stay home with her children, which was a significant financial sacrifice.

--Some talked about the fact that their religious values clashed with materialism and said the tension between the two could result in stress. An Amish Menonite woman, for instance, talked about the stress of feeling disconnected from other women because she doesn't dress like them or care about money and status in the same way.

A few participants talked about both positive and negative impacts of religion on their financial stress, LeBaron said. Differences were not observed between respondents' religious affiliations, which were: 34% from various Protestant denominations; 28% Catholic; 12% nondenominational Christian; 10% Islamic; 5% Hindu, Buddhist or Baha'i; 4% Jewish; 3% Mormon; and 3% other Christian denominations.

LeBaron said she hopes her findings will help provide a better understanding - for both religious and non-religious people - of how religion can interact with family finance.

"The take-home message for people who are religious or people who work with religious people - like counselors, therapists or religious leaders - is to be open to the idea that religion can have benefits and also drawbacks," LeBaron said. "It's good to understand both because then you're in a better place to mitigate the drawbacks and optimize the positive aspects."

LeBaron said future studies should continue to explore the relationship between religion and financial stress, and why that relationship might differ from person to person.

"Religion and finance are an interesting combination of things to look at because they are two things that are very salient to some families," she said. "Religion and money both impact their daily life, so hopefully more studies will take both into account in the future."

Credit: 
University of Arizona

CEOs' political leanings skew firms' logic in structuring initial pay package

video: Prior research has shown that political affiliation is an indicator of a CEOs willingness to take risk-- liberal CEOs are bigger risk takers than their conservative counterparts. Timothy Hubbard, assistant professor of management in the University of Notre Dame's Mendoza College of Business, set out to find evidence that conservative CEOs, consequently, receive more performance based pay to incentivize them to take more risks for the firm, but instead, he found the opposite is true in "The influence of CEO risk tolerance on initial pay packages," forthcoming in Strategic Management Journal.

Image: 
University of Notre Dame

When firms design the initial pay package for a new CEO, they focus on that person's tolerance or aversion to risk-taking. Research and corporate governance practices generally recommend compensating a risk-averse CEO with more performance-based pay to incentivize risk taking.

Prior research has shown that political affiliation is an indicator of a CEO's willingness to take risk -- liberal CEOs are bigger risk-takers than their conservative counterparts. New research from the University of Notre Dame set out to examine whether conservative CEOs receive more performance-based pay to incentivize them to take more risks for the firm, but instead, they found the opposite is true.

Newly appointed, conservative CEOs who are naturally more risk averse receive less performance-based pay than those who are more willing to take risks, and more liberal CEOs get more performance-based pay, according to "The influence of CEO risk tolerance on initial pay packages," forthcoming in Strategic Management Journal from Timothy Hubbard, assistant professor of management in Notre Dame's Mendoza College of Business, along with Scott Graffin and Eric Lee from the University of Georgia and Dane Christensen from the University of Oregon.

It happens, Hubbard explains, through a process of matching (CEOs join firms that compensate the way they prefer) and tailoring (boards tailor pay to the individual CEO).

"Our study shows new CEO compensation mirrors their existing risk preferences," he says. "CEOs are attracted to firms that offered the prior CEO a pay package that is similar to what they would naturally want to have -- or appeals to their risk tolerance. And there's a little bit of tailoring happening where the new CEO is receiving a different pay package based on their personal risk preferences as measured through their political orientation."

In an effort to understand how CEOs might change a firm after their appointment, the team challenged the traditional wisdom that if you want change within a firm, the board should load up the CEO with incentive-based pay. Instead, they incorporated into their research the differences between individual CEOs.

"This is really important," Hubbard says, "because when we look at how CEOs change the strategy of their firms, we find that conservative CEOs don't react to performance-based pay, whereas with liberal CEOs, as you increase the performance-based pay, they end up changing the firm a lot more. This leaves open the question for boards and shareholders: How do you encourage more conservative-leaning CEOs to enact strategic change? This study shows that increasing performance-based pay does not result in conservatives enacting strategic change."

The team looked at 739 CEOs at 485 companies in the S&P 500 between 1995 and 2011 and measured CEOs' political orientation based on their political giving. Their performance-based pay was determined by how much of their salary was conditional on firm performance -- stock options, bonuses -- compared to their salaries. To investigate the effect of political orientation and initial pay on change, they looked at changes in resource allocation patterns at firms, their level of merger activity and changes in research and development.

Credit: 
University of Notre Dame

How LISA pathfinder detected dozens of 'comet crumbs'

image: Illustration of LISA Pathfinder

Image: 
NASA's Goddard Space Flight Center

LISA Pathfinder, a mission led by ESA (the European Space Agency) that included NASA contributions, successfully demonstrated technologies needed to build a future space-based gravitational wave observatory, a tool for detecting ripples in space-time produced by, among other things, merging black holes. A team of NASA scientists leveraged LISA Pathfinder's record-setting sensitivity for a different purpose much closer to home -- mapping microscopic dust shed by comets and asteroids.

Most of these particles, known as micrometeroids, have masses measured in micrograms, similar to a small grain of sand. But at speeds reaching 40,000 mph (64,000 kph), even micrometeoroids pack a punch.

The NASA team, led by Ira Thorpe at NASA's Goddard Space Flight Center in Greenbelt, Maryland, detected 54 impacts during the mission, which lasted from 2015 to 2017. Modeling the strikes allowed the researchers to determine what kinds of objects shed the dust. The findings are broadly consistent with existing ideas of what generates micrometeroids found near Earth. The dusty culprits are mostly short-period comets whose orbits are determined by Jupiter. Comets with longer periods, like Halley's comet, also contributed dust that LISA Pathfinder sensed.

The new measurements could help refine dust models used by researchers in a variety of studies, from understanding the physics of planet formation to estimating impact risks for current and future spacecraft.

Credit: 
NASA/Goddard Space Flight Center

Superbug battle: Bacteria structure may be key to new antibiotics

ITHACA, N.Y. - Cornell researchers have uncovered the structure of a regulatory mechanism unique to bacteria, opening the door for designing new antibiotics targeted to pathogens.

As the threat of antibiotic-resistant germs grows, this discovery offers hope for finding an alternative way to target disease-causing bacteria.

In the study, researchers used X-ray crystallography to reveal the structure of so-called "T-box" elements in the pathogen Mycobacterium tuberculosis, the model bacterium in the study.

T-boxes are structures that recognize when a cell is deficient in a specific amino acid, the building blocks of cells. T-boxes allow bacteria to respond to this deficiency by initiating a process that generates more of that amino acid. In this way, T-boxes facilitate basic functioning in bacteria, including many pathogens such as M. tuberculosis and Bacillus anthracis, which causes the deadly anthrax disease.

"The T-boxes are only found in bacteria and they control essential genes," said study first author Robert Battaglia. "This makes them an attractive target because they are also essential for a lot of these bacteria to respond to starvation conditions."

Battaglia is a graduate student in the lab of senior author Ailong Ke, professor of molecular biology and genetics at Cornell University.

T-boxes bind to an essential macromolecule called tRNA, which exists in uncharged and charged forms. Different types of tRNA are each fitted to a specific type of amino acid. When the amount of an amino acid is low in the bacteria cell, the corresponding tRNA will be uncharged and will bind to a T-box, which in turn recognizes what type of amino acid that tRNA requires and facilitates a process of generating more of that amino acid. When the amount of an amino acid goes up, the tRNA will couple with it, thereby charging that tRNA. The amino acids are then used in all kinds of basic bacteria cell functions.

In the study, the researchers described the structure of the full T-box and tRNA complex.

"By solving our structure, we're able to see how different parts of the T-box are positioned to allow the T-box to have this specific interaction with a tRNA," Battaglia said. "If we can develop some sort of drug to target these T-box elements to mess with their ability to bind with the tRNA, they could be a really good choice for an antibiotic because we don't have [T-boxes] ourselves, so we don't have to worry about side effects or toxicity."

Credit: 
Cornell University