Culture

Why an early start is key to developing musical skill later in life

Among the many holiday traditions scuttled by pandemic restrictions this year are live concerts featuring skilled musicians. These gifted performers can often play with such ease that it is easy to underestimate the countless hours of practice that went into honing their craft.

But could there be more to mastering music? Is there, as some have suggested, a developmental period early in life when the brain is especially receptive to musical training? The answer, according to new research published in the journal Psychological Science, is probably not.

"It is a common observation that successful musicians often start their musical training early," said Laura Wesseldijk, a researcher at the Karolinska Institute in Sweden and first author on the paper. "One much-discussed explanation is that there may be a period in early childhood during which the brain is particularly susceptible to musical stimulation. We found, however, that the explanation to why an early start matters may be more complicated and interesting than previously believed."

While the new study supports the idea that an early start is associated with higher levels of musical skills and achievement in adulthood, the underlying reasons for this may have more to do with familial influences--such as genetic factors and an encouraging musical family environment--along with accumulating more total practice time than those who start later in life.

To untangle these effects, Wesseldijk and her colleagues recruited 310 professional musicians from various Swedish music institutions, such as orchestral and music schools. The researchers also used data from an existing research project, the Study of Twin Adults: Genes and Environment (STAGE). Participants from both studies were tested on musical aptitude and achievement. They also answered a series of questions that gauged how often they practiced and the age of onset of musical training. The STAGE data also provided genetic information on its participants.

By comparing the results from these two independent studies, the researchers were able to show that an earlier start age is associated with musical aptitude, both in amateurs and professional musicians, even after controlling for accumulated practice time. They then evaluated starting age in a manner that accounted for the genetic data from the STAGE study.

The results indicate that genetic factors--possibly related to musical interest and talent--have a substantial influence on the age individuals start music practice and their future musical aptitude. When controlling for familial factors, namely shared genetic and environmental influences, such as a home environment that is steeped in music, there was no additional association between an earlier start age and musicality.

A possible explanation for these results could be that children who display more talent in a particular field, such as music, are encouraged to start practicing earlier. Another possibility is that a musically active, interested, and talented family provides a musical environment for the child, while also passing on their genetic predispositions to engage in music.

"I think we have really investigated effects of the age you start musical training to the fullest," said Wesseldijk. "Personally, as someone who practices music, it is always great to shed light on some of the factors, within the gene environmental interplay, that influence music skills."

Credit: 
Association for Psychological Science

Cornell University to extract energy from manure to meet peak heating demands

image: An integrated biorefinery approach utilizing agriculture waste biomass to produce renewable biomethane along with other co-products (for soil amendment, nutrient recovery, and transportation biofuels).

Image: 
Nazih Kassem, with images from Cornell University, Department of Energy

WASHINGTON, December 22, 2020 -- Cornell University is developing a system to extract energy from cattle manure to meet the campus's peak demands for heat in the winter months. In the Journal of Renewable and Sustainable Energy, by AIP Publishing, scientists involved with the project give a detailed analysis of the issues required to make this work, including scientific, economic, and energy policy considerations.

The university is already involved in an initiative to develop renewable energy sources and services, with the goal of reducing its carbon footprint by 100% by 2035. These goals are proving difficult to achieve in cold regions, such as Ithaca, New York, where the university is located, since over six months of winter heating is needed for its buildings and laboratories.

Heating needs are a significant portion of Cornell's energy usage, and a challenge occurs at peak heating times. The university is developing a geothermal project that provides heat from hot water extracted 3-4 kilometers underground. This will provide adequate base-level heating but would be economically unattractive to meet peak demand.

To meet the need for more heat in the depths of winter, the investigators are proposing a system to convert cattle manure from the school's dairy farms, which house 600 cows, to methane and other products. The method employs a three-stage process, where the manure is first biologically digested with microbes to produce biogas, a mixture of carbon dioxide and methane.

This is followed by a second stage that converts the digested manure into a type of biocrude oil plus a substance called hydrochar that makes a good soil amendment.

The final stage combines the carbon dioxide generated in the first step with hydrogen gas produced by renewable electrolysis of lake water to biologically generate renewable natural gas, RNG. This final product can be injected into the natural gas grid for New York state, in much the same way electricity from wind turbines and solar panels is returned to the electrical grid.

"The proposed system will produce about 909 million liters of RNG per year," said author Nazih Kassem. "This can provide 97% of the total annual peak heating demand. The remainder can be met by purchasing natural gas, increasing Cornell's dairy herd size, or using campus eateries' food wastes for co-digestion. Adding 19 more dairy cows would result in enough RNG production to meet the average annual peak heating demand."

The investigators' detailed economic analysis revealed the importance of state policies regarding the RNG price and other issues.

"If New York state were to adopt policies to create a carbon market and enable competitive RNG pricing, then the proposed biomass peak heating system would show profitability," Kassem said.

Credit: 
American Institute of Physics

Use of diagnosis code for COVID-19 among US hospitalizations

What The Study Did: Researchers examined the use of COVID-19-specific coding, the transition from legacy coding and the accuracy of the COVID-19-specific code using SARS-CoV-2 polymerase chain reaction (PCR) testing as the reference standard.

Authors: Ning Rosenthal, M.D., Ph.D., M.P.H., of Premier Healthcare Solutions in Charlotte, North Carolina, is the corresponding author.

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

(doi:10.1001/jama.2020.20323)

Editor's Note: The articles includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Assessing progress in health care quality through lens of COVID-19

What The Viewpoint Says: Observations about health system performance during the COVID-19 pandemic are offered in this Viewpoint, with an emphasis on system cohesion and 2 of 3 levels of health care described earlier by the National Academy of Medicine: health care organizational capabilities and the environment of care.

Authors: Carolyn M. Clancy, M.D., of the Discovery, Education and Affiliate Networks (DEAN), Department of Veterans Affairs in Washington, D.C., is the corresponding author.

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

(doi:10.1001/jama.2020.17392)

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

Credit: 
JAMA Network

Pregnant women in third trimester unlikely to pass SARS-CoV-2 infection to newborns

Pregnant women who are infected with SARS-CoV-2, the virus that causes COVID-19, during the third trimester are unlikely to pass the infection to their newborns, suggests a study funded by the National Institutes of Health. The study followed 127 pregnant women who were admitted to Boston hospitals during the spring of 2020. Among the 64 pregnant women who tested positive for SARS-CoV-2, no newborns tested positive for the virus. NIH support was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID).

"This study provides some reassurance that SARS-CoV-2 infections during the third trimester are unlikely to pass through the placenta to the fetus, but more research needs to be done to confirm this finding," said Diana W. Bianchi, M.D., NICHD Director.

The study, published in the journal JAMA Network Open, was led by Andrea G. Edlow, M.D., M.Sc., of Massachusetts General Hospital and Harvard Medical School.

The researchers studied the occurrence of SARS-CoV-2 infection in the third trimester of pregnancy, evaluating levels of virus in respiratory, blood and placental tissue samples, the development of maternal antibodies, how well those antibodies passed through the placenta to the fetus (an indicator of potential immune protection from the mother) and examined placental tissue. The results reported are limited to women in the third trimester because data on women infected during the first and second trimesters are still being collected and evaluated.

Among those who tested positive for SARS-CoV-2 in the study, 36% (23/64) were asymptomatic, 34% (22/64) had mild disease, 11% (7/64) had moderate disease, 16% (10/64) had severe disease, and 3% (2/64) had critical disease. The study included, as comparators, 63 pregnant women who tested negative for SARS-CoV-2 and 11 reproductive-age women with COVID-19 who were not pregnant.

The team found that pregnant women who were positive for SARS-COV-2 had detectable levels of virus in respiratory fluids like saliva, nasal and throat secretions, but no virus in the bloodstream or the placenta.

The researchers did not find significant differences between levels of SARS-CoV-2 antibodies produced by pregnant and non-pregnant women. However, the study team did observe lower-than-expected levels of protective antibodies in umbilical cord blood. In contrast, they found high levels of influenza-specific antibodies, presumably from maternal flu vaccination, in the cord blood samples of both SARS-CoV-2 positive and negative women. The researchers suggest these findings may indicate that SARS-CoV-2 antibodies do not pass through the placenta as easily as other maternal antibodies.

The researchers believe theirs is one of the first reports of less-than-expected transfer of SARS-CoV-2 antibodies to the fetus. Low transfer of these antibodies was observed regardless of the woman's severity of COVID-19 or whether she had an underlying health condition, such as obesity, high blood pressure or diabetes. The study authors noted that it will be important to determine why these maternal antibodies are less likely to cross the placenta and whether this reduced antibody transfer renders newborns more vulnerable to SARS-CoV-2 infection, compared to other infections. The authors added that it will be important to determine how lower levels of maternal SARS-CoV-2 antibodies may affect health outcomes of preterm babies because COVID-19 may increase the risk of preterm labor.

The study also found that placentas from infected women were not different from those of uninfected women, though the risk for ischemia (reduced blood flow) in the placenta appeared higher for women with more severe COVID-19. In line with an earlier report, the researchers also found that while the placenta expresses major molecules used by SARS-CoV-2 to cause infection--the ACE2 receptor and the TMPRSS2 enzyme--the two molecules are rarely expressed together in the same location, which may help explain why the virus only rarely affects the placenta.

The researchers suggest their findings could help improve the care of pregnant women with COVID-19 and of their newborns, as well as provide information to assist in the development of new strategies for vaccinating pregnant women.

Credit: 
NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development

Community-based programs reduce sexual violence, study shows

image: When community leaders engage teenage boys in programming designed to either teach healthy masculinity or job readiness skills, reports of sexual violence among the boys went down.

Image: 
UPMC

PITTSBURGH, Dec. 22, 2020 - Through small, neighborhood classes, researchers at UPMC Children's Hospital of Pittsburgh and Promundo-US significantly reduced sexual violence among teenage boys living in areas of concentrated disadvantage.

The study, published today in JAMA, is the culmination of a large Centers for Disease Control and Prevention clinical trial spanning 20 racially segregated neighborhoods in the Pittsburgh area to evaluate two violence prevention programs. The proportion of youth reporting the use of sexual or partner violence in their relationships decreased in both groups by about 12 percentage points.

"To accomplish something like this requires nurturing community partnerships," said study senior author Elizabeth Miller, M.D., Ph.D., chief of adolescent and young adult medicine at UPMC Children's Hospital of Pittsburgh. "In each of these neighborhoods, we worked with community members to facilitate the programs with an eye toward sustainability."

Between 2015-2017, nearly 900 boys between the ages of 13-19 enrolled in these small group programs, which were run by community leaders from each neighborhood.

Half of the sites were randomized to receive job readiness training and the other half were assigned a curriculum called "Manhood 2.0," which is based on Promundo's "Program H" in Brazil. The "H" stands for hombres.

"Manhood 2.0 engages young men in questioning harmful ideas about manhood," said Promundo-US Chief Executive Officer Gary Barker. "It calls men into being part of the solution to ending violence in intimate partner relationships and helps them see the benefits to healthier manhood in their own lives."

Manhood 2.0 was adapted for young men in U.S. urban communities, but the core message remains the same: challenging gender norms that foster violence against women and unhealthy sexual relationships.

For young men enrolled in Manhood 2.0, the use of partner violence--including physical or verbal abuse, sexual harassment, sexual coercion and cyber abuse--dropped from 64% at baseline to 52% in the months following the program. For those who received job training, self-reported sexual violence dropped from 53% to 41%.

That was a surprise. Miller said she expected job training to have a positive impact in other areas of life, but not violence towards women.

"Job skills training is a structural intervention, grounded in economic justice," Miller said. "Perhaps this resonated and resulted in young men using less violence because they felt more hopeful about their future."

Next, the researchers hope to study whether combining Manhood 2.0 with job readiness training might have an even greater impact on intimate partner and sexual violence than either curriculum alone.

"We know that young men often need job skills and opportunities to discuss healthy relationships and healthier manhood," Barker said. "Combining these two proven approaches seems particularly promising and necessary."

Additional authors on the study include Kelley Jones, Ph.D., Alison Culyba, M.D., Ph.D., Taylor Paglisotti, M.P.H., Namita Dwarakanath, Michael Massof, M.P.A., and Zoe Feinstein of UPMC Children's Hospital; Katie Ports, Ph.D., at the Centers for Disease Control and Prevention; Dorothy Espelage, Ph.D., of the University of North Carolina at Chapel Hill; Julie Pulerwitz, Sc.D., of the Population Council; Aapta Garg, M.A., and Jane Kato-Wallace, M.P.H., of Promundo-US; and Kaleab Z. Abebe, Ph.D., of the University of Pittsburgh School of Medicine.

Funding was provided by the Centers for Disease Control and Prevention (grant U01CE002528).

To read this release online or share it, visit http://www.upmc.com/media/news/122220-Miller-JAMA-Manhood [when embargo lifts].

Credit: 
University of Pittsburgh

Strategies for adults experiencing sheltered homelessness during COVID-19 pandemic

What The Study Did: In this modeling study of simulated adults living in homeless shelters, daily symptom screening with polymerase chain reaction (PCR) testing of individuals who had positive symptom screening paired with management at a nonhospital care site of people with mild to moderate COVID-19 was associated with a substantial decrease in infections and lowered costs over four months compared with no intervention across a wide range of epidemic scenarios.

Authors: Kenneth A. Freedberg, M.D., M.Sc., of the Massachusetts General Hospital in Boston, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.28195)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Pregnant women with COVID-19 pass no virus but fewer-than-expected antibodies to newborns

BOSTON -- Pregnant women may be especially vulnerable to developing more severe cases of COVID-19 following SARS-CoV-2 infection, but little is known about their anti-SARS-CoV-2 immune response or how it may affect their offspring. In a study published in JAMA Network Open, a group led by investigators at Massachusetts General Hospital (MGH) provides new insights that could help improve care for these women and their newborns and emphasizes the need for pregnant women to be considered in vaccine rollout plans.

The study included 127 pregnant women in their third trimester who received care at three Boston hospitals between April 2 and June 13, 2020. Among the 64 women who tested positive for SARS-CoV-2, investigators detected no virus in maternal or cord blood (despite detection in the women's respiratory system), no signs of the virus in placentas and no evidence of viral transmission to newborns. The researchers suspect that transmission to the fetus may be blocked not only due to the lack of virus in the mothers' blood, but also because the major molecules used by SARS-CoV-2 to enter cells (ACE2 receptor and TMPRSS2 enzyme) are often not physically located together in the placenta.

Most of the women who tested positive developed antibody responses against SARS-CoV-2 proteins, but mother-to-newborn transfer of anti-SARS-CoV-2 antibodies through the placenta was significantly lower than transfer of anti-influenza antibodies.

"Our finding of compromised mother-to-baby transfer of SARS-CoV-2-specific antibodies in third trimester infections has implications for maternal vaccine administration. Specifically, it highlights that pregnant women are a key population to consider in vaccine rollouts. It also raises questions regarding the optimal timing of vaccine administration to best support maternal and newborn immunity," says lead author Andrea Edlow, MD, a maternal-fetal medicine specialist at MGH and an assistant professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School.

Edlow notes that transplacental transfer of antibodies to the fetus is typically highest in the third trimester, so it was unexpected to see significantly reduced transfer of SARS-CoV-2 antibodies relative to those against influenza. "Understanding the mechanisms underlying this inefficient transfer of SARS-CoV-2-specific antibodies after third trimester infection, as well as understanding whether vaccine-generated antibodies have the same or different properties than those from actual infection with the virus, will be critical directions for future research," she says.

Credit: 
Massachusetts General Hospital

Controlling cardiac waves with light to better understand abnormally rapid heart rhythms

image: In Chaos, researchers use mice to study tachycardias and find there are intrinsic mechanisms that exist in heart tissue that they hypothesize lead to the self-termination of rapid cardiac rhythm.

Controllable reentry in a light-sensitive heart: (top left) Activation map during fixed delay pacing; (top right) Alternans (beat-to-beat changes) in voltage; (bottom) The same plot over a longer period shows self-terminating bursts.

Image: 
Gil Bub

WASHINGTON, December 22, 2020 -- Over 300,000 people die each year in the U.S. due to sudden cardiac death. In many cases, sudden cardiac death is caused by abnormally rapid heart rhythms called tachycardias, which means the heart cannot pump adequate blood to the body.

In Chaos, by AIP Publishing, researchers use mice to study tachycardias and find there are intrinsic mechanisms that exist in heart tissue that they hypothesize lead to the self-termination of rapid cardiac rhythm.

"A tachycardia is a heartbeat continuously activating the heart, like a toy train endlessly going around a circular track," said co-author Leon Glass.

The researchers modeled tachycardias in a mouse heart by detecting the wave in one part of the heart and stimulating another part at a fixed time later. They discovered that small changes in the delay lead to either endless circulation or self-termination of the cardiac waves.

During the circulation of the wave and before the termination, there was often an alternation of wave characteristics, such as one cycle proceeding faster and the next being slower. The researchers used optogenetics, a set of tools that allows them to stimulate and control cardiac waves with light, rather than by standard methods of electrical stimulation.

Alternating dynamics, called alternans, in the heart have been associated in the past with initiation of tachycardias. Consequently, efforts have been made to eliminate or reduce alternans.

"Paradoxically, we find that alternans can also facilitate self-termination of tachycardia and might be beneficial," said co-author Gil Bub.

The optical, real-time feedback control system can be used for a wide variety of innovative experiments beyond this specific research.

"We could extend the work to study control of other geometries of abnormal cardiac wave propagation such as spiral waves. It can also be applied to the nervous system where there are abnormal bursting rhythms such as epilepsy," said co-author Leonardo Sacconi.

The team plans to build on this research in several ways, including carrying out similar experiments in cardiac cell culture and investigating how drugs impact the stability of tachycardias, characterizing the molecular and ionic mechanisms facilitating self-termination of the tachycardia, and modifying the magnitude of the alternans to analyze its role in the self-termination of tachycardia.

Credit: 
American Institute of Physics

Keeping up appearances: male fairy-wrens show looks can be deceiving

image: The researchers found that all male superb fairy-wrens produced and maintained vibrant colours, regardless of their 'natural quality'.

Image: 
Alex McQueen

In many animals, female preference for males with the most elaborate appearance is an important factor in the evolution of bright and dramatic colours.

Females are thought to prefer colourful males because only 'high-quality' males - those with the most resources, superior foraging skills or social status - can produce and maintain the most vibrant colours.

By choosing these high-quality males, females may ensure a good father or good genes for their offspring.

But do high quality males that are preferred by females invest more in their appearance?

A new study by Monash University ornithologists suggests, not necessarily.

Led by PhD graduate Dr Alex McQueen, from the Monash University School of Biological Sciences the study published in Behavioural Ecology examined whether conspicuous colours of superb fairy-wrens signal male quality.

"We examined whether only the best quality males with excellent resources can produce the most vibrant colours and whether only the best quality males can maintain their colours in pristine condition," said Alex. "We also tested this in an experiment, by administering testosterone to some males which caused them to produce breeding colours in winter."

"Surprisingly, we found that all male superb fairy-wrens produced and maintained vibrant colours, regardless of their 'natural quality'. Also the males that had to produce breeding colours in challenging winter conditions displayed vibrant colours that were indistinguishable from other males," she said.

Every year male superb fairy-wrens change colour by moulting from a brown non-breeding plumage to an ultraviolet blue and black breeding plumage.

While they are in their breeding plumage, males flaunt their colours to females by performing elaborate sexual displays.

"We predicted that maintaining their colours would be especially important in this species for two reasons: first, males that are preferred by females produce their breeding plumage earlier than all other males, many months before the start of breeding, meaning that those early males display their breeding colours for the longest time each year; and second, ultraviolet blue feathers have been shown to readily fade over time in other birds," said Alex.

The research team measured the colours of the same, wild male fairy-wrens several times a year.

And they recorded how much time males spent preening when they were in their brown non-breeding plumage and colourful breeding plumage.

"We were very surprised to find that male breeding colours do not fade with time," said Alex.

"Despite keeping their colours in pristine condition, males did not spend more time preening while in breeding plumage," she said.

The research team found that instead males 'retouched' their breeding colours by replacing a few blue feathers at a time throughout the breeding season.

"Our study shows that the vibrant breeding colours of male superb fairy-wrens are unlikely to signal male quality to females," said Alex.

"We also found that males are careful to keep their feather colours in excellent condition for sexual displays."

Credit: 
Monash University

Variation in US hospital mortality rates for patients admitted with COVID-19 during the 1st 6 months of pandemic

What The Study Did: Researchers used data from a large national health insurer in the U.S. to examine whether hospital outcomes for patients with COVID-19 are improving.

Authors: David A. Asch, M.D., of the University of Pennsylvania in Philadelphia, is the corresponding author.

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

(doi:10.1001/jamainternmed.2020.8193)

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

Credit: 
JAMA Network

Cannabis use blunts stress reactivity in female rats

Female rats that inhaled vaporized cannabis daily for a month developed a blunted physiological response to stress, according to a new study by Washington State University researchers.

In contrast, male rats that were provided access to the same potency of cannabis over the same 30-day window did not experience any physiological changes in how they responded to a stressful situation.

The results of the study, published in the journal Neurobiology of Stress, indicate there may be significant differences in how chronic cannabis use affects males and females.

The WSU scientists' work also establishes a direct, experimental relationship between chronic cannabis use and dampened stress reactivity.

"We were able to show pretty conclusively that chronic cannabis use can, in fact, significantly dampen stress reactivity in female rats," said Carrie Cuttler, an assistant professor of psychology at WSU and co-author of the study.  "Until now, no one has been able to establish whether this blunted stress response is the cause or the consequence of cannabis use."

One of the main reasons why scientists haven't been able to link smoking cannabis to a muted stress response is that in human studies they can't practically or ethically randomly assign their test subjects to use cannabis or prevent them from consuming the drug for a period of time before beginning an experiment.

Because of these and other issues, researchers interested in examining chronic effects of cannabis use have tended to rely on animal models, where rats are injected with isolated components of cannabis to study the effects of the drug.

"The problem with this approach is that it's stressful to the rats and doesn't recruit the same neurobiological circuits that taking a drug of your own volition does," said Ryan McLaughlin, an assistant professor of integrative physiology and neuroscience at WSU and a co-author on the paper.  "To address this challenge, we developed a more natural cannabis delivery system that enables rats to self-administer vaporized cannabis whenever they feel like it."

For the study, McLaughlin and his team trained rats to poke their noses into a hole with an infrared beam inside whenever they wanted a puff of cannabis vapor. The researchers then measured levels of the stress hormone corticosterone before and after a 30-day period in male and female rats that were either put into a control group that was not given cannabis or one of three experimental test groups that were given access to cannabis of low, medium, or high potencies.

Initially, all of the rats had similar spikes in corticosterone levels when confronted with a stressful situation.

After the 30-day self-administration period, only the female rats that had access to the medium potency cannabis demonstrated a significantly muted physiological response. The rats that were given access to the medium potency cannabis also tended to respond more for the substance and had higher concentrations of the drug in their blood after the experiment which may explain why this group specifically demonstrated the blunted stress response.

"Interestingly, we found that the rats that were given access to higher potency cannabis tended to respond less and had lower concentrations of THC in their blood after the experiment than the rats that had access to the medium potency cannabis," McLaughlin said. "What is causing this difference as well as why females seem to be more receptive to the stress muting effects of cannabis are both things we plan to investigate in the future."

While McLaughlin and Cuttler's work suggests cannabis might have some benefits in conferring resilience to stress, the two researchers emphasized the release of stress hormones typically serves an adaptive purpose, allowing an individual to mobilize energy stores and respond appropriately to threats in the environment.

"An inability to mount a proper hormonal response to stress could have detrimental effects that could potentially be harmful to the individual," Cuttler said. "Research on cannabis is really just now ramping up because of legalization, and our work going forward will play an important role in better understanding both the benefits and potential consequences of chronic cannabis use in women and men."

Credit: 
Washington State University

BioAFMviewer software for simulated atomic force microscopy of biomolecules

image: Schematic illustration of the BioAFMviewer functionality. Computational AFM scanning transforms any biomolecular structure provided in the standard PDB file format into a corresponding simulated AFM graphics.

Image: 
Kanazawa University

Abstract: Atomic force microscopy (AFM) allows to obtain images and movies showing proteins at work, however with limited resolution. The developed BioAFMviewer software opens the opportunity to use the enormous amount of available high-resolution protein data to better understand experiments. Within an interactive interface with rich functionality, the BioAFMviewer computationally emulates tip-scanning of any biomolecular structure to generate simulated AFM graphics and movies. They greatly help in the interpretation of e.g., high-speed AFM observations.

Nowadays nanotechnology allows to observe single proteins at work. Under atomic force microscopy (AFM), e.g., their surface can be rapidly scanned, and functional motions monitored, which is of great importance for applications in all fields of Life science. The analysis and interpretation of experimental results remains however challenging because the resolution of obtained images or molecular movies is far from perfect. On the other side, high-resolution static structures of most proteins are known, and their conformational dynamics can be computed in molecular simulations. This enormous amount of available data offers a great opportunity to better understand the outcome of resolution-limited scanning experiments.

The developed software provides the computational package towards this goal. The BioAFMviewer computationally emulates AFM scanning of any biomolecular structure to generate graphical images that resemble the outcome of AFM experiments (see Fig. 1). This makes the comparison of all available structural data and computational molecular movies to AFM results possible. The BioAFMviewer has a versatile interactive interface with rich functionality. An integrated 3D viewer visualizes the molecular structure while synchronized computational scanning with adjustable tip-shape geometry and spatial resolution generates the corresponding simulated AFM graphics. Obtained results can be conveniently exported as images or movies.

To demonstrate the great potential of simulated AFM scanning in supporting the analysis and interpretation of experimental data, the authors provide several applications to high-speed AFM observations of proteins. As an example, for the gene scissor related CRISPR-associated protein 9 endonuclease (Cas9), simulated scanning allows to disambiguate the domain arrangement seen in the high-speed AFM image and clarify their orientation with respect to the bound nucleotide strand (see Fig. 2). The authors furthermore demonstrate how the BioAFMviewer can transform molecular movies of proteins, obtained for example from molecular modeling, into corresponding simulated AFM movies. Therefore, simulated AFM experiments are possible and can be compared to the movies recorded in high-speed AFM experiments to better understand the resolution-limited observed conformational dynamics.

The BioAFMviewer has a user-friendly interface and no expert knowledge is required to use it. The software is already used by AFM groups worldwide, and it is expected to become a standard platform used by the broad community of Bio-AFM experimentalists. Beyond that, it also provides the interface for researchers from the fields of computational biology and bioinformatics to foster their interdisciplinary collaborations.

The BioAFMviewer software package is currently available for the Windows 10 operating system. A free download is provided on the project website http://www.bioafmviewer.com, where also future updates will become available.

The BioAFMviewer software project was initiated by Holger Flechsig, who is an Assistant Professor of the Nano Life Science Institute at Kanazawa University, Japan, where world-leading AFM experiments of biological matter are performed. The first author, Romain Amyot has developed the software package and continues to work on future applications. Besides that, he also performs high-speed AFM experiments of proteins as a postdoctoral researcher at the Aix-Marseille University, France.

Credit: 
Kanazawa University

Visible hydrogels for rapid hemorrhage control and monitoring

image: Shear-Thinning Hydrogel

Image: 
Khademhosseini Lab

(LOS ANGELES) - There are many different events which may lead to excessive and uncontrolled bleeding within the body. This can occur as a result of inflammation and ulcerations, abnormalities in the blood vessels or trauma-related injuries. Individuals with predisposing conditions, such as cardiac patients, are at particular risk of internal bleeding due to the anticoagulants they are often prescribed as a preventive measure. They are also prone to gastrointestinal bleeds, affecting 40% of patients who are on cardiac assistance devices. In addition to the need for an effective treatment for these conditions, there are also indications for controlling the blood flow that contribute to aneurysms and tumor cell vascularization.

An ideal treatment method would quickly and effectively block the break in the affected blood vessels to stop the bleeding and allow the vessel wall to heal. Then the blocking material would eventually degrade enough to allow the blood to flow again normally.

Current treatments involve both solid and liquid materials as blocking agents. Coils made of braided platinum or stainless steel wires are commonly used. They come in a variety of lengths, shapes and thicknesses and are placed into blood vessels using a special catheter. There are also liquid blocking agents that are injected into the blood vessels and solidify after injection.

But there are many difficulties in using the current methods. Because coils need special catheters for insertion and specialized equipment to detach and place them, the procedure is difficult and requires intensive training by the physician. Also, there are times when multiple coils need to be placed in order to be effective, and there are other times where the coils migrate or compact, necessitating repeat procedures. Liquid agents often leak during injections, resulting in inaccurate placement, toxic effects on the surrounding tissues and the necessity for additional attempts. These problems raise the potential for added time and cost.

In addition, neither of these methods have the ability to accurately view the procedures by conventional CT, MRI, X-ray and fluoroscopic methods. Successful imaging would greatly help to guide placement and to monitor the blood vessel block over time.

A previous study by the authors has used inexpensive, gelatinous materials called hydrogels in an attempt to produce an effective material for controlling hemorrhage. In addition to having superior biocompatibility and tunable elastic and mechanical properties, hydrogels also exhibit sheer-thinning capabilities - the ability to deform upon injection and then quickly self-recover and mold itself to fit the desired space; this allows delivery to be made using standard catheters without specialized equipment. Silicate nanoplatelet discs were mixed into the hydrogel to mimic the clotting ability of platelet cells, and the resultant composite proved to be highly effective at sealing off damaged veins.

A collaborative team of clinical intervention radiology specialist and bioengineering researchers has taken this project a step further by adding imaging particles made from tantalum hydrogel mixture. Tantalum, a highly biocompatible metal, has been shown to be safe to use in biomedical applications and is excreted in the urine.

The team made of scientists from the Terasaki Institute and Mayo Clinic performed various tests to determine the optimum tantalum particle size and quantity to use and their effect on the mechanical properties of the hydrogel composite. They also established the optimum formulation for the three components of their new composite gel. Their experiments determined that the tantalum particles dispersed well into the hydrogel composite, did not affect its mechanical properties and retained their sterility over time.

Another ambitious goal of the project was to perform their hemorrhage control experiments on arteries something that had not been done with hydrogels before. This effort posed additional challenges, due to the higher blood flow and pressure in arteries, their wide size variation and their potential fragility.

After various experiments conducted on the arterial vessels of live anticoagulated porcine models, the team obtained positive results with their new tantalum-laced composite hydrogel. They were able to create an effective seal against bleeding in the pigs' arteries, with a deployment time that was 40 times faster than with coils. The arterial block also exhibited stability and durability, staying in position without migration for four weeks before degrading naturally and being replaced by connective tissue repair of the vessel.

Due to the tantalum component in the gel the animal models' arterial procedures and monitoring were performed with clear, real-time visualization using CT, X-ray fluoroscopy and ultrasound.

"The experimental results that were observed in our tantalum-loaded gel clearly demonstrate its effectiveness and versatility", said HanJun Kim, a member of the Terasaki Institute's team. "We were able to meet our goals of being able to visualize and accurately place a stable block in an arterial vessel to rapidly treat uncontrolled intravascular hemorrhage."

The team went on to conduct additional experiments to test the reversibility of the new hydrogel's arterial placement and found that their solidified arterial plug could easily be removed using an aspirational catheter. They were also able to obtain successful arterial blockage by applying their hydrogel composite to coils that had been placed in the vessels and had failed to achieve or sustain blockage.

The use of this tantalum-loaded gel to control bleeding exhibits many unique advantages over current methods. It is a safe, easy-to-use, and cost effective method which demonstrates optimum effectiveness, precision and versatility for a variety of potential medical applications.

"The treatment method developed here are a vast improvement over current methods and it has the potential to affect many lives," said Ali Khademhosseini, Ph.D., director and CEO for the Terasaki Institute. "It is one of many examples of the innovative and impactful work that we do at our institute."

Credit: 
Terasaki Institute for Biomedical Innovation

Wi-Fi technology with fiber optic-like performance for Industry 4.0

image: A UOC research developed with the ALBA Synchrotron

Image: 
Sergio Ruiz (ALBA synchrotron)

Despite significant advances in wireless technology, the manufacturing industry continues to turn to wired forms of communication such as Ethernet or fibre optics for its most critical tasks. A new study by Cristina Cano and the full professor Xavier Vilajosana, researchers from the Wireless Networks (WiNe) group at the Internet Interdisciplinary Institute (IN3), opens the door to the use of wireless technologies with power and reliability that are comparable to fibre optics and that could replace cabled connections. The research project, published in the journal IEEE Transactions on Wireless Communications, has created the first parameterization of a millimetre-band signal propagation model, a wireless technology capable of transmitting a huge amount of data per second, in an industrial environment. According to the researchers, this new model is the first step towards understanding how this type of signal behaves in an industrial plant and could have a significant impact on the development of Industry 4.0.

Cristina Cano said: "This study is aimed at making communication less expensive and more flexible by incorporating mobile devices into the manufacturing process, something that could be very useful in moving towards Industry 4.0, since it allows, for example, connecting freely movable robotic arms to the production process or establishing communications for data reporting, and controlling or stopping the different components of the process in an emergency. But it could also allow the worker to be a part of the process."

A unique study at the ALBA synchrotron

Before implementing millimetre bands in industrial settings, it is necessary to understand how they propagate in such a distinctive environment. There are currently several propagation models of this type of high-frequency signal, but none in industrial facilities. Cano said: "A model is a representation of reality that, using equations, allows us to predict what will happen to the signal in each environment. There are several models for millimetre bands in office and urban settings, but there are hardly any in industrial settings. These sorts of facilities differ in many ways which could interfere with the behaviour of the wireless signal, such as the height of the ceiling, the material of the walls and floors, or the type of machinery they contain. Our research has allowed us, for the first time, to establish the parameters for an industrial environment."

The researchers were able to measure the behaviour of this type of signal at the ALBA synchrotron, an electron accelerator located in Barcelona that enables researchers from all over the world to carry out experiments using synchrotron light, chosen because its facilities have characteristics that resemble different industrial environments in large production plants, such as refrigeration facilities, server rooms or experimental halls. "It is very difficult for the scientific community to access a manufacturing plant for testing, which is why we believe that this type of model has taken so long to be parameterized. We have been able to advance in this investigation thanks to the ALBA synchrotron, which allowed us access to its facilities. These facilities are very similar to those that we might find in an industrial setting and, also, since we carried out the tests when the accelerator ring was stopped, we were able to access the interior and experiment with the signal in these bands in such a specific environment. We believe that it has been a unique opportunity," explained the researcher.

By measuring in this environment we have been able to verify that typical surfaces in industrial plants, such as reflective pipes, are very beneficial for this type of communication, since they allow the signal to travel along various paths and reception is reinforced, allowing greater coverage. "Specifically, we were able to establish a 110-metre link, the largest communication link achieved with the IEEE 802.11ad standard to date," highlighted the researcher.

Model accessible to the research community

This model is the first step towards understanding how this type of signal behaves in this environment, but protocols must be established to guarantee the reliability required for this sort of communication by the manufacturing industry in its critical processes. The researcher said: "The research in this field can be applied to replace cables in the monitoring processes of production lines where very quick and reliable decisions have to be taken."

She continued: "For this reason, we must be able to guarantee that when an emergency message is sent to stop the production process, it arrives in the required time and its reception is highly reliable. Otherwise, if the message is lost or arrives late, the consequences could be disastrous."

In order to expedite the drafting of these protocols, the new model is accessible to the entire research community. By way of conclusion, Cano said: "The parameters that we provide in the article are useful to predict how the signal will behave in an industrial environment. They can, for example, be configured in a simulator to simulate different configurations and obtain a result that reflects the real situation. In this way, it can help other researchers to design protocols that guarantee the correct functioning of the network."

Credit: 
Universitat Oberta de Catalunya (UOC)