Culture

Climate skeptics not easily persuaded by available evidence, now or later

EUGENE, ORE. -- May 27, 2021 -- Climate skeptics who aren't persuaded by the existing evidence from climate change are unlikely to change their minds for many years, according to a newly published quantitative study by a University of Oregon environmental economist

The central question posed by the study published in the journal Climate Change was "How much evidence would it take to convince skeptics that they are wrong?" The answer depended on the degree of skepticism. The study modeled two types of hypothetical skeptics -- those who were less extreme and believed the change in temperature was slight, as well as more extreme skeptics who believed the change was nonexistent -- and exposed them to climate data recorded between 1866 and 2005, as well as future projections until the end of the century.

"If a climate sceptic is unpersuaded by the evidence that is already available to them today, my model implies that they will likely remain a skeptic for many years into future," said author Grant McDermott, an assistant professor in the University of Oregon Department of Economics interested in the interaction between human and natural systems. "Why? Because it suggests their prior beliefs are so strong that even decades of continued warming may not be enough to convince them."

Moderate skeptics on the other hand were highly likely to change their beliefs once given more evidence of recorded temperature change.

A secondary goal of the paper was to bridge competing theories of climate skepticism as a social phenomenon by looking closely at "source credibility" from the skeptic's perspective. In other words, McDermottt said, there is a need to acknowledge that many skeptics regard mainstream sources of climate science as untrustworthy. They may not trust scientists over their own sources, which in turn could help to explain why they don't update their beliefs as scientists provide more information.

"One implication of that is that if you're trying to think about who to target with messaging to persuade people that climate change is a real and observable phenomenon, you should just accept that some people you're just not going to convince, even with more years' worth of evidence."

Because McDermott employed a quantitative model, he calls the project "a grandiose thought experiment" that uses "hypothetical, stylized skeptics." While some climate scientists have employed complicated supercomputer models, McDermott's Bayesian mathematical model uses simpler, standard econometric techniques - bread and butter to environmental economists like him. At its essence, the model provides a framework for combining prior beliefs with new information and seeing how beliefs are updated.

McDermott suggests that further research could be directed to disentangle the root causes of strongly-held skeptic beliefs. Specifically, are skeptics extremely sure of their priors, or simply mistrustful of scientific sources about climate change? Or, perhaps it is some combination of the two?

"The actions of others may often seem irrational to us, and vice versa, but it's important to recognize that a person's actions are, more than likely, perfectly congruent with their internal belief system," McDermott said. "Acknowledging that is an important first step towards crafting effective public policy."

Credit: 
University of Oregon

Not fear, but goal importance and others' behavior makes you favour COVID-19 measures

While earlier research has mostly looked into factors such as fear, perceived risk, age and political views to determine what makes individuals and societies more or less willing to drastically change their lifestyle and support government-imposed strict restrictions, in order to mitigate the spread of the COVID-19 pandemic, psychologists at the University of Zurich Charlotte Kukowski, Katharina Bernecker and Veronika Brandstätter took a different perspective.

Instead, they chose to find out the impact of people's perception of others' behaviour when it comes to the public good, as well as people's own self-control in sticking to behaviour guidelines. By using data from the United Kingdom and Switzerland, they concluded that, indeed, valuing fair contribution to the public good and the ability to practice self-control make people more likely to undertake health-protective behaviour, though the effects for self-control are not entirely consistent across the countries the authors sampled. Further, people who are more concerned with the cooperation of their fellow citizens and expect them to do their own part are more supportive of government regulations, possibly as a means of ensuring that others comply. However, the authors stress that future studies need to test this possible link. The study is published in the peer-reviewed, open-access scientific journal Social Psychological Bulletin.

Successfully overcoming conflicting desires and needs, such as taking public transportation, meeting with friends, and participating in large gatherings, for the benefit of society means that people must practice self-control. People will only be willing to control their desires and needs, however, if they value the higher goal, that is, managing the pandemic, even though their own health-protective behavior might not affect them directly. In this sense, self-control in the service of a societal goal is quite different from self-control for a personal goal, such as sticking to a healthy diet or meeting career goals.: While exercising and career achievements are largely private concerns, we all depend on each other's cooperation when it comes to a societal goal like managing COVID-19 pandemic. Therefore, in the context of the COVID-19 pandemic, higher goal importance and perception of others' behavior are key factors in practicing health-protective behavior.

"(...) we would like to emphasise that the effects of self-control and cooperation emerged above and beyond the effects of variables such as personal cost of engaging in health-protective behaviors, perceived risk and anxiety, and political orientation. If future work replicates these findings, one might cautiously conclude that, in a time of crisis, people - including decision-makers - are indeed able to "rise above themselves" and lay aside political differences and personal costs for collective goal attainment," say the researchers.

The authors note that in collective actions, it is essential that one sees others put in the same effort.

In conclusion, the scientists note that, in order to improve public efforts in combating the COVID-19 pandemic, as well as other collective goals, including climate change mitigation, it is essential that we identify the factors contributing to successful self-control and cooperation in the service of higher, society-level goals.

Credit: 
The Polish Association of Social Psychology

Fight against antibiotic-resistant bacteria has a glowing new weapon

image: A new chemical probe glows in the presence of a bacterial enzyme that contributes to antibiotic resistance.

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The University of Texas at Austin

AUSTIN, Texas -- In the perpetual arms races between bacteria and human-made antibiotics, there is a new tool to give human medicine the edge, in part by revealing bacterial weaknesses and potentially by leading to more targeted or new treatments for bacterial infections.

A research team led by scientists at The University of Texas at Austin has developed chemical probes to help identify an enzyme, produced by some types of E. coli and pneumococcal bacteria, known to break down several common types of antibiotics, making these bacteria dangerously resistant to treatment.

"In response to antibiotic treatment, bacteria have evolved various mechanisms to resist that treatment, and one of those is to make enzymes that basically chew up the antibiotics before they can do their job," said Emily Que, assistant professor of chemistry and one of the leading researchers on the team. "The type of tool we developed gives us critical information that could keep us one step ahead of deadly bacteria."

In a paper published online yesterday in the Journal of the American Chemical Society, the researchers zeroed in on the threat posed by the bacterial enzyme called New Delhi metallo-beta-lactamase (NDM). They set out to create a molecule that glows when it comes into contact with the NDM enzyme. When these chemical probes are added to a test tube, they bind to the enzyme and glow. Such a tool could be used to alert doctors to what kind of bacterial threat is affecting their patients and tell them which antibiotics to use.

NDM breaks down antibiotics in the penicillin, cephalosporin and carbapenem classes, which are some of the safest and most effective treatments for bacterial infections. Other classes of antibiotics exist, but they may carry more side effects, have more drug interactions and may be less available in some parts of the world.

In addition to indicating the presence of the NDM enzyme, the florescent chemical probe developed by Que and Walt Fast, a professor of chemical biology and medicinal chemistry, may help find a different way to combat these resistant bacteria. One treatment option that doctors use with resistant bacteria is to combine common antibiotics and an inhibitor. Although there is no known clinically effective inhibitor for NDM-producing bacteria, Que's probe could help find one.

Once the probe has bound to the enzyme and begun to glow, if an effective inhibitor is introduced, it will knock the probe loose and the glow would stop. This allows scientists to test a high volume of potential drugs very quickly--research Que and Fast hope to continue in the future.

"This allows us to work towards developing therapies and eventually understanding evolutionary characteristics of such proteins," said Radhika Mehta, a recent UT Austin doctoral graduate and lead author on the paper. Mehta is currently a postdoctoral fellow in the Merchant Lab at the University of California, Berkeley.

The study also examined a process called nutritional immunity, which comes from the human body's production of proteins in response to an infection. The proteins snatch up all the available metals in the body, such as the zinc required to make NDM, rendering the bacteria more susceptible to attack.

"The evolution of this bacteria since its discovery in 2008 indicates that not only is it developing antibiotic resistance, it's attempting to combat this natural human immune process. That's particularly scary," Que said.

Que's probe can also be used to study nutritional immunity and NDM because it will glow only in the presence of the zinc needed to form the enzyme.

Credit: 
University of Texas at Austin

Exploring optimization of duplex velocity criteria for diagnosis of ICA stenosis

Study Exploring Optimization of Duplex Velocity Criteria for Diagnosis of Internal Carotid Artery (ICA) Stenosis Published Online

Online first in Vascular Medicine, researchers from the Intersocietal Accreditation Commission (IAC) Vascular Testing division report findings of their multi-centered study of duplex ultrasound for diagnosis of internal carotid artery (ICA) stenosis. 1

The study was developed in response to wide variability in the diagnostic criteria used to classify severity of ICA stenosis across vascular laboratories nationwide and following a survey of members of IAC-accredited facilities supporting efforts toward standardization.2 The primary objective of the study was to evaluate widely used SRU Consensus Criteria (SRUCC) and, if needed, to propose further optimization to these criteria.3

Researchers found that carotid duplex interpretation using SRUCC produced significant overestimation of stenosis for both moderate (50-69%) and severe (> 70%) ICA lesions as determined by catheter angiography. The authors conclude that laboratories currently using SRUCC should consider modification of existing criteria to incorporate more stringent and accurate parameters for ICA stenosis greater than 50% by increasing the peak systolic velocity (PSV) threshold to > 180 cm/sec or requiring the ICA/CCA PSV ratio > 2.0 in addition to PSV of > 125 cm/sec.

"This study reflects more than six years of work of a team of IAC staff and multi-specialty volunteers with case study materials collected from 11 centers nationwide. While the SRUCC are broadly used, they had never been formally compared to the gold-standard of catheter angiography. We have shown that use of SRUCC overestimated degree of ICA stenosis and identify potential opportunities for modifications that can ultimately enable greater accuracy and consistency in ICA interpretation across vascular laboratories," said lead investigator, Heather L. Gornik, MD, IAC Vascular Testing Immediate Past-President.

"Through its use of real world data from IAC-accredited vascular laboratories, this paper highlights the opportunity to improve the quality of care for patients with carotid disease," said Tatjana Rundek, MD, PhD, IAC Vascular Testing President. "By modifying existing criteria to incorporate more accurate parameters and implementing these criteria broadly, the accuracy of diagnostic ultrasound testing can be improved across our vascular community."

As a next step, IAC Vascular Testing will disseminate a white paper document summarizing the study results and providing guidance to vascular laboratories for implementation of criteria and further steps toward standardization across the vascular testing community. The complete study report can be accessed through open access of Vascular Medicine at https://journals.sagepub.com/doi/full/10.1177/1358863X211011253. The authors' affiliations and disclosures of conflicts of interest and a listing of participating study centers are available in the article.

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Intersocietal Accreditation Commission

Aging: Clinical trial on potential reversal of epigenetic age using a diet and lifestyle

image: Intervention group age change. Participants scored an average of 1.96 years younger than baseline (p=0.066). Of 18 participants included in the final analysis, 8 scored age reduction, 9 were unchanged, and 1 increased in methylation age.

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Correspondence to: Kara N. Fitzgerald email: kf@drkarafitzgerald.com

Aging published "Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial" which reported on a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients.

Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock (also published in Aging).

The diet and lifestyle treatment was associated with a 3.23 years decrease in DNAmAge compared with controls.

DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to the same individuals at the beginning with a strong trend towards significance.

This randomized controlled study, published in Aging, suggests that specific diet and lifestyle interventions may reverse Horvath DNAmAge epigenetic aging in healthy adult males.

This randomized controlled study, published in Aging, suggests that specific diet and lifestyle interventions may reverse Horvath DNAmAge epigenetic aging in healthy adult males.

The study’s lead author, Kara Fitzgerald ND IFMCP, from The Institute for Functional Medicine said, "Advanced age is the largest risk factor for impaired mental and physical function and many non-communicable diseases including cancer, neurodegeneration, type 2 diabetes, and cardiovascular disease."

Methylation clocks are based on systematic methylation changes with age.

DNAmAge clock specifically demonstrates about 60% of CpG sites losing methylation with age and 40% gaining methylation.

Almost a quarter of the DNAmAge CpG sites are located in glucocorticoid response elements, pointing to a likely relationship between stress and accelerated aging. Cumulative lifetime stress has been shown to be associated with accelerated aging of the methylome.

Other findings include that PTSD contributes to accelerated methylation age; and that greater infant distress is associated with an underdeveloped, younger epigenetic age.

This is to say the authors have tentatively accepted the hypothesis that the methylation pattern from which the DNAmAge clock is computed is a driver of aging, thus they expect that attempting to directly influence the DNA methylome using diet and lifestyle to set back DNAmAge will lead to a healthier, more “youthful” metabolism.

The Fitzgerald Research Team concluded in their Aging Research Output, "it may be that emerging ‘omics’ approaches continue to evolve our understanding of biological age prediction and reversal beyond DNA methylation alone. Integration of our future understanding of multi-omics data should therefore be considered in the future trials of candidate age-delaying interventions."

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Impact Journals LLC

Books on health, economic inequalities in Latin America, Caribbean shed light on content, impact of health policies

More than 500,000 people have died from COVID-19 in Latin America and the Caribbean, demonstrating the health and economic inequalities throughout the region. A new article analyzes seven books* that discuss these inequalities, including questions of who gets health care and what interdependent roles societies, social movements, and governments play. To end inequality in the region, the author calls for a universal approach to health care.

The article, by a professor at Carnegie Mellon University (CMU), appears in the June 2021 issue of Latin American Research Review, a journal published by the Latin American Studies Association.

"These books break new ground and contribute to our understanding of some of the most important health care systems in Latin America," says Silvia Borzutzky, teaching professor of political science and international relations at CMU's Heinz College, who wrote the article. "In so doing, they help us understand the content and impact of health policies, an issue that has taken on new urgency during the pandemic."

With the seven books as a backdrop, the author begins with a brief historical overview of health policies in the region, then examines the role of social movements, subnational governments, and policy implementation in ensuring access to health care. She also addresses the role of international organizations.

Borzutzky notes that most of the books' authors are concerned with equitable and universal health care policies, but that this goal has been hampered. Even in countries with a universal right to health care, citizens have unequal access due to regional inequalities, traditional patronage relations, and the exclusion of minorities or minoritized groups.

During the COVID-19 pandemic, individuals who lack power have borne the brunt of this lack of access. In addition, because illness results from poverty, in a post-pandemic Latin America and Caribbean, the task will be not only to provide universal, good-quality health care but also to reduce poverty across the continent, suggests the author.

"The authors of the books I reviewed are clear that health policies in this part of the world are far from universal," Borzutzky explains. "Instead, they are fragmented and respond to the power and actions of critical groups or individuals in critical roles at specific times and places."

Borzutzky suggests that to end inequality and expand health care to all in this region, Latin America and the Caribbean need a universal approach based on equity and inclusion, and the recognition that health care should not be parceled out in regional, economic, gender, or ethnic terms. She argues that only this approach will allow the people in the region to fulfill their capabilities and contribute to their societies' development and success.

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Carnegie Mellon University

Bacterium causing rabbit fever remains virulent for months in cold water

image: Northern Arizona University professor David Wagner, director of the Pathogen and Microbiome Institute's (PMI) Biodefense and Disease Ecology Center, led a study to better understand the life cycle and behavior of F. tularensis, funded through a $2.25 million grant from the U.S. Defense Threat Reduction Agency (DTRA).

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Northern Arizona University

Although it is not spread through human contact, Francisella tularensis is one of the most infectious pathogenic bacteria known to science--so virulent, in fact, that it is considered a serious potential bioterrorist threat. It is thought that humans can contract respiratory tularemia, or rabbit fever--a rare and deadly disease--by inhaling as few as 10 airborne organisms.

Northern Arizona University professor David Wagner, director of the Pathogen and Microbiome Institute's (PMI) Biodefense and Disease Ecology Center, began a three-year project in 2018 to better understand the life cycle and behavior of F. tularensis, funded through a $2.25 million grant from the U.S. Defense Threat Reduction Agency (DTRA).

One of the most puzzling behaviors of the pathogen is its ability to remain dormant, possibly in what is called a "viable but nonculturable" state--which means the bacteria is alive, but cannot be grown in the laboratory. That makes it much more difficult to study, because scientists can typically only study bacteria that can be cultured. Wagner's goal was to study the bacterium so as to determine the environmental and genetic factors that contribute to the pathogen's ability to apparently remain dormant for months at a time--a phenomenon that has remained mostly a mystery despite more than 100 years of research.

Now, Wagner and his collaborators have published their findings, "Long-Term Survival of Virulent Tularemia Pathogens outside a Host in Conditions That Mimic Natural Aquatic Environments," in the journal Applied and Environmental Microbiology. In the paper, the team shows how they were able to prove, by replicating environmental conditions in the lab, including low temperatures and low-nutrient water, that the bacterium can persist for months in cold water without any nutrients and remain fully virulent. Their results provide a plausible explanation for how it can overwinter in the environment outside of a host.

"We are making some very interesting discoveries in this project," Wagner said. "The main finding is that Francisella tularensis can persist in a dormant state for more than six months in cold water without any nutrients. This means it has the ability to persist in the environment outside of a mammalian host or arthropod vector. This was unexpected because many other bacteria that persist like that long-term in the environment form spores when they are outside of a host, such as Bacillus anthracis, the bacterium that causes anthrax forms spores, but F. tularensis doesn't do that. Others, like Yersinia pestis - the bacterium that causes plague - are always either in a mammalian host or a flea vector. F. tularensis has the ability to persist long-term in the environment long-term outside of a host without forming spores while remaining fully virulent."

"These study results have completely changed our perspective on the ecology of this bacterium. We now understand that mammals are likely just a small (but still important) aspect of its survival strategy. We now think that it spends most of its time in the environment outside of a host and only periodically causes disease in mammals. But those disease events in mammals are still very important as they serve to amplify the amount of F. tularensis that is deposited back in the environment."

Working with co-principal investigator Jason Sahl, associate professor and assistant director of PMI, and with PMI senior research scientists Dawn Birdsell and Joe Busch, Wagner conducted the study along with colleagues at two of the team's long-term collaborating institutions in Sweden: The Swedish Defence Research Agency and Umeå University.

Along with their Swedish collaborators, Wagner and his team are known worldwide for their work developing the phylogeny, or global family tree, of F. tularensis and its phylogeography--mapping where different groups of the species are found throughout the world and understanding the species' genetic diversity.

"As we continue with the DTRA research grant, we are now investigating the genes and proteins that regulate the ability of F. tularensis to persist in the environment outside of mammals and hosts. This work involves a number of current and recently graduated undergraduate students at NAU: former student Kathleen Soria, current students Natalie Hart and Rebecca Ballard, and current student and Flinn Scholar Kailee Savage.

Although the bacteria are naturally occurring throughout the northern hemisphere, including Arizona, the number of reported cases in the U.S. is small, with only 230 cases in 2016, three of which occurred in Arizona. Humans can be infected through insect bites; by drinking contaminated water, which happens in developing countries such as Turkey; by handling infected animals; and by breathing aerosolized particles containing the bacteria. Humans cannot transmit the disease to other humans. There is no vaccine to prevent the disease, which is treated with antibiotics. Wagner's team recently completed a related project funded by the DTRA studying the pathogen's antibiotic resistance.

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Northern Arizona University

Key early steps in gene expression captured in real time by CSU researchers

On scales too small for our eyes to see, the business of life happens through the making of proteins, which impart to our cells both structure and function. Cellular proteins get their marching orders from genetic instructions encoded in DNA, whose sequences are first copied and made into RNA in a multi-step process called transcription.

A research collaboration at Colorado State University specializes in high-resolution fluorescence microscopy and computational modeling to visualize and describe such stuff-of-life processes in exquisite detail, in real time, at the level of single genes. Now, scientists led by postdoctoral researcher Linda Forero-Quintero have, for the first time, observed early RNA transcription dynamics by recording where, when and how RNA polymerase enzymes kick off transcription by binding to a DNA sequence.

The breakthrough technology, detailed in the journal Nature Communications, has countless possible outshoots; these include sharpening understanding of basic biological processes, to unveiling the genetic underpinnings of certain diseases.

"This is the first time someone has looked at RNA polymerase phosphorylation dynamics in a single-copy gene," said Forero, who is a postdoctoral researcher co-advised by Tim Stasevich, Monfort Professor and associate professor in biochemistry, and Brian Munsky, associate professor in chemical and biological engineering. In the past, such early transcription activity could only be visualized using gene arrays, which are artificial structures composed of hundreds of copies of a gene and not commonly found in the cell nucleus.

Stasevich and Munsky lead a collaboration funded by the W.M. Keck Foundation and the National Institute of General Medical Sciences (through two Maximizing Investigators' Research Awards) that's seeking to unveil and quantify real-time genetic expression in living, single cells. Forero, who works in both labs under the auspices of the collaboration, had previously studied proteins and transporters in cell membranes associated with neurological conditions.

Early transcription activity

As described in Nature Communications, Forero et al. designed a method using an established mammalian cell line, engineered fluorescent antibody fragments, and a custom super resolution microscope to capture the process of early transcription in vivid colors: blue, green and red. More specifically, they observed the start of the transcription cycle that happens when the RNA polymerase II (RNAP2) transcription enzyme becomes phosphorylated, or decorated with phosphate groups, on its amino acid tail.

"The interdisciplinary science here is a fantastic blending of new experimental capabilities and a new approach for mechanistic computational modeling of single-cell dynamics, both of which are very novel in their respective fields," said Munsky, who supervises the computational aspects of the collaboration.

In the lab, the researchers loaded their antibody fragments into an established mammalian cell line containing a reporter gene that when transcribed, is lit up by a fluorescently tagged protein. The antibody fragments, which Stasevich helped develop several years ago, are tagged with fluorescent molecules that light up their specific targets in the RNAP2 tail. Using these tagging technologies together, the researchers could distinguish three distinct steps in the transcription cycle, marked by different colors. The images obtained with this system translate into fluorescent intensity fluctuation. The researchers then used those signals to interpret the spatiotemporal organization of RNAP2 phosphorylation throughout the transcription cycle at a single-copy gene.

New information via computational model

Munsky's team led by graduate student William Raymond took Forero and Stasevich's microscopy data and translated it into a computational model based on stochastic differential equations. By fitting this statistical model to reproduce all the experimental results, the computational team then extended their analyses to glean new mechanistic and quantitative information about the different molecules and their states through the transcription process.

For example, they estimated how many individual RNA polymerase molecules collect to form transient clusters in the region of the DNA's promoter, how long these clusters persist, and how, when and where the polymerases distribute themselves along the DNA. They found, for example, that each burst of transcription activity produces a cluster of between five and 40 RNA polymerases to form around the promoter region of the gene, of which 46% eventually succeed to transcribe RNA. They also found that each RNA takes approximately five minutes to be fully transcribed and processed prior to release.

Forero says the technology has far-reaching potential, especially combined with newer technologies like CRISPR, in which specific genes can be singled out and manipulated. Choosing a certain gene of interest, say one implicated in a disease, and applying the CSU researchers' real-time readout of the transcription cycle, could then allow researchers to watch disease processes happening at the activity level of single genes.

"The ability to resolve the spatial and temporal dynamics of the transcription cycle, in one gene, is the most exciting aspect of this work," Forero said.

Credit: 
Colorado State University

Mouse pups' cries give clues about autism spectrum disorder

image: Noboru Hiroi, PhD, and collaborators are studying which mouse pup cries are most predictive of the pups developing autism spectrum disorder later. Dr. Hiroi is a professor at The University of Texas Health Science Center at San Antonio.

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The University of Texas Health Science Center at San Antonio

SAN ANTONIO (May 27, 2021) — One-fifth of babies who inherit a genetic variant located on chromosome 16 will develop autism spectrum disorder (ASD) by age 3. The variant is called 16p11.2 deletion.

Noboru Hiroi, PhD, of The University of Texas Health Science Center at San Antonio (also referred to as UT Health San Antonio), is studying mice that have this deletion. The team, which includes colleagues from Japan, Ireland and the U.S., is harnessing the power of machine learning to understand which vocalizations of the newborn mouse pups are most predictive of social abnormalities one month later when the pups reach puberty.

“It is essential to identify those very early signs that can predict what is to come, because if we can translate what we discover in mouse pups to human infants and apply therapeutic options earlier, their outcome will be better,” Dr. Hiroi said.

Mice are studied because of the short timeline of their development. The same research in human babies, which is just beginning, will take two to three years of follow-up. In May, collaborators led by Cynthia Blanco, MD, professor of pediatrics and the Greehey Family Foundation Chair in Neonatology Research at UT Health San Antonio, started recording the cries of preterm infants in the University Hospital neonatal intensive care unit. Preterm infants are targeted because of their high risk of developmental issues, including ASD.

Disordered cries

When mouse pups are separated from their mothers, they emit ultrasonic vocalizations in a certain order. Mouse mothers respond to the cries and take care of their offspring.

The cries are abnormal in mice with the 16p11.2 deletion.

“Pups that carry this genetic variation cannot form the correct sequence,” Dr. Hiroi said. “We want to know whether those abnormal sequences or combinations of call types can predict what is to come one month later in their social behaviors.”

Machine learning will enable the team to develop a precise diagnostic algorithm for ASD. “The point is, once we can do this with the mouse vocalizations, we can apply the same algorithm to the cries of human babies,” Dr. Hiroi said.

Earlier intervention

Infants at risk of ASD who are identified in this way can be given desensitization therapy so that they don’t overreact to certain cues they don’t like, he said. And behavioral therapies can be applied to help babies learn how to cope in social situations.

The research is described in a paper published in the journal Molecular Psychiatry.

The authors point out that algorithms developed from infant vocalizations could be used to predict other disorders, such as schizophrenia, which develops 17 to 20 years after birth.

The mice also display abnormality in their responses to social olfactory cues. Normal mice presented with another mouse respond by sniffing. The mutant mice don’t respond to that cue, Dr. Hiroi said.

Acknowledgments

Dr. Hiroi, recruited to UT Health San Antonio in 2019 from the Albert Einstein College of Medicine, is a professor in the departments of pharmacology, cellular and integrative physiology, and cell systems and anatomy within the university’s Joe R. and Teresa Lozano Long School of Medicine.

This research is made possible by a grant (R01DC015776) to Dr. Hiroi from the National Institute on Deafness and Other Communication Disorders, part of the National Institutes of Health. The Department of Psychiatry and Behavioral Sciences at UT Health San Antonio also provided startup funds for this project.

Computational identification of variables in neonatal vocalizations predictive for postpubertal social behaviors in a mouse model of 16p11.2 deletion

Mitsuteru Nakamura, Kenny Ye, Mariel Barbachan e Silva, Takahira Yamauchi, Daniel J. Hoeppner, Amir Fayyazuddin, Gina Kang, Emi A. Yuda, Masako Nagashima, Shingo Enomoto, Takeshi Hiramoto, Richard Sharp, Itaru Kaneko, Katsunori Tajinda, Megumi Adachi, Takuma Mihara, Shinichi Tokuno, Mark A. Geyer, Pilib Ó Broin, Mitsuyuki Matsumoto and Noboru Hiroi

First published: April 15, 2021, Molecular Psychiatry

https://www.nature.com/articles/s41380-021-01089-y

The University of Texas Health Science Center at San Antonio, also referred to as UT Health San Antonio, is one of the country’s leading health sciences universities and is designated as a Hispanic-Serving Institution by the U.S. Department of Education. With missions of teaching, research, patient care and community engagement, its schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have graduated more than 37,000 alumni who are leading change, advancing their fields, and renewing hope for patients and their families throughout South Texas and the world. To learn about the many ways “We make lives better®,” visit www.uthscsa.edu.

Stay connected with The University of Texas Health Science Center at San Antonio on Facebook, Twitter, LinkedIn, Instagram and YouTube.

To see how we are battling COVID-19, read inspiring stories on Impact.

Journal

Molecular Psychiatry

DOI

10.1038/s41380-021-01089-y

Credit: 
University of Texas Health Science Center at San Antonio

Hip replacement surgery improves symptoms and biomechanics -- but not physical activity

May 27, 2021 - Patients undergoing total hip arthroplasty (THA) show significant reduction in pain and other symptoms and improvement in walking gait biomechanics. However, those improvements do not lead to increased daily physical activity levels, reports a study in The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

The findings "present a worrying picture that while patients have the opportunity to be more physically active through improvements in functional capacity, their physical behaviors do not change," according to the new research, led by Jasvir S. Bahl of the University of South Australia, Adelaide, in collaboration with the University of Adelaide, Flinders University, and the Royal Adelaide Hospital. The researchers call for additional efforts to help patients get up to a healthy level of physical activity following THA.

Nearly all patients remain sedentary after THA

The prospective study included 51 patients with an average age of 66 years who underwent primary THA at a public hospital in South Australia. All procedures were performed using the same surgical technique and implant type. Prior to the procedure, data were recorded for several patient-reported domains, including hip-related symptoms, function, and quality of life.

In addition, patients underwent gait analysis and musculoskeletal modeling for in-depth analysis of biomechanics and overall walking performance. They also completed 24-hour physical activity monitoring with use of a wrist-worn activity tracker (accelerometer). In a subgroup of patients, gait analysis and activity monitoring were repeated at one and two years postoperatively.

At both follow-up times, patients reported improvements in pain and other hip-related symptoms, hip function, and everyday quality of life. Gait analysis showed improvement in almost every aspect of walking biomechanics, including walking speed and step length.

However, 24-hour activity monitoring showed little or no change in daily physical activity patterns. Both preoperatively and postoperatively, patients were sedentary or asleep for 19.5 hours of the day, on average. This finding remained significant after adjusting for age, body mass index, and occupation.

In fact, there was evidence that sedentary time increased after THA. The percentage of patients who were sedentary for more than 11 hours per day increased from 25 percent preoperatively to 31 percent at one year and 41 percent at two years postoperatively. At all assessment points, patients reported that most of their active time was spent in light physical activity.

Activity monitoring also provided information on the patient sleep time and quality. Average sleep time remained the same, at about nine hours per night. However, sleep efficiency declined year over year, from 84 percent preoperatively to 80 percent at one year and 77 percent at two years postoperatively, with less than 85 percent considered inefficient sleep.

Consistent with many previous studies, these results show that THA leads to "significant and substantial" improvements in pain, function, and quality of life. However, the present study shows that despite these improvements, few patients change their daily physical activity patterns in the two years after THA.

"Evidently, a surgical procedure alone may not enable patients to lead a more physically active lifestyle," Dr. Bahl and coauthors write. Although the study cannot draw conclusions about the reasons why physical activity did not improve, previous reports have suggested that low activity patterns may become "hard-wired" after years of physical disability. The authors also suggest that if patients have to wait several years before THA, they may become used to a more sedentary lifestyle.

Dr. Bahl and colleagues note that patients undergoing hip replacement surgery often have accompanying health conditions such as high blood pressure, obesity, and diabetes that are best managed with increased physical activity and exercise. The researchers conclude: "Health-care providers must consider a multifaceted model of care, which includes patient education on the importance of reducing sedentary behaviors, and addressing a range of barriers and facilitators to increase physical activity postoperatively."

Credit: 
Wolters Kluwer Health

Versatile coronavirus antibody may be starting point for broader-acting vaccines

LA JOLLA, CA--Even before the COVID-19 pandemic, most people in the United States already had been sick with a coronavirus, albeit a far less dangerous one. That's because at least four coronaviruses in the same general family as SARS-CoV-2 cause the benign yet annoying illness known as the common cold.

In a new study that appears in Nature Communications, scientists from Scripps Research investigated how the immune system's previous exposure to cold-causing coronaviruses impact immune response to COVID-19. In doing so, they discovered one cross-reactive coronavirus antibody that's triggered during a COVID-19 infection.

The findings will help in the pursuit of a vaccine or antibody treatment that works against most or all coronaviruses, says senior author Raiees Andrabi, PhD, an investigator in the Department of Immunology and Microbiology.

"By examining blood samples collected before the pandemic and comparing those with samples from people who had been sick with COVID-19, we were able to pinpoint antibody types that cross reacted with benign coronaviruses as well as SARS-CoV-2," says Andrabi, who works closely with the laboratory of professor Dennis Burton, PhD.

In later tests, the antibody also neutralized SARS-CoV-1, the coronavirus that causes SARS, or severe acute respiratory syndrome.

"We were able to determine that this type of cross-reactive antibody is likely produced by a memory B cell that's initially exposed to a coronavirus that causes the common cold, and is then recalled during a COVID-19 infection," Andrabi says.

Memory B cells are an essential part of the immune system. They "remember" initial disease threats and can circulate in the bloodstream for decades, ready to be called back into action if the threat emerges again. These cells are responsible for producing targeted antibodies.

The discovery may be an important step in the eventual development of a pan-coronavirus vaccine, which would be able to protect against potential coronaviruses that emerge in the future, says Burton, the James and Jessie Minor Chair in Immunology in the Department of Immunology & Microbiology at Scripps Research.

"Another deadly coronavirus will likely emerge again in the future--and when it does, we want to be better prepared," Burton says. "Our identification of a cross-reactive antibody against SARS-CoV-2 and the more common coronaviruses is a promising development on the way to a broad-acting vaccine or therapy."

Burton's lab is also investigating broadly neutralizing antibodies that can be harnessed to protect against many forms of influenza, which is another virus likely to cause a pandemic in the future.

In the new study, the team used electron microscopy to understand how the cross-reactive antibody is able to neutralize a range of coronaviruses. They saw that it mostly binds to the base of the virus's spike protein, an area that doesn't change much from strain to strain, says first author Ge "Sophie" Song, a graduate student in the Burton laboratory.

"The study highlights how important it is to fully understand the nature of preexisting immunity, especially in regard to coronaviruses," Song says. "Earlier exposure to a coronavirus, even a benign virus that causes colds, impacts the nature and level of antibodies produced when more serious coronavirus threats emerge."

Credit: 
Scripps Research Institute

Research news tip sheet: Story ideas from Johns Hopkins Medicine

JOHNS HOPKINS MEDICINE RESEARCHERS SHOW HOW AIR POLLUTION MAY CONTRIBUTE TO LOSS OF SMELL

Media Contact: Waun'Shae Blount, wblount1@jhmi.edu

The loss of smell, a condition known as anosmia, can severely impact a person's quality of life, making it extremely difficult to taste foods, detect airborne hazards in the environment and carry out other functions dependent on the sense. Those with anosmia may experience weight concerns, decreased social interaction, depression and general anxiety. In some cases, loss of smell has been linked to death in older adults. Now, Johns Hopkins Medicine researchers have studied one of the known causes of anosmia -- long-term exposure to air pollution -- to better understand how it can rob someone of the ability to smell and taste.

The findings appeared May 27, 2021, in JAMA Network Open.

"We included participants from a variety of areas in our study; however, most lived in urban areas where pollution levels are highest," says lead author Murugappan "Murray" Ramanathan, M.D., rhinologist and associate professor of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medicine. "We wanted to assess how their exposure to PM2.5 air pollution -- inhalable, particulate matter less than 2.5 micrometers in size or about 30 times smaller than the diameter of a human hair -- might cause them to lose their sense of smell."

According to the U.S. Environmental Protection Agency (EPA), PM2.5 (the PM stands for "particulate matter") is the term for a mixture of solid particles and liquid droplets found in the air. Depending on location, PM2.5 can consist of many materials, incuding dust, dirt, soot, smoke, organic compounds and metals. It has been linked to cardiovascular disease, lung cancer, decline in cognitive thinking ability, chronic obstructive pulmonary disease, asthma and premature death. Previous research has associated PM2.5 as a likely culprit in loss of smell -- a connection that Ramanathan and his team decided to explore in greater detail.

In their study, the researchers looked at 2,690 people, age 18 and older, who were evaluated by otolaryngologists between January 2013 and December 2016. Of these, 538 were diagnosed with anosmia, with an average age of 54 and with men making up the majority (339 or 63%).

Air pollution data for the study came from the EPA's Air Quality System. The researchers fed the data into a complex computer model -- incorporating meteorological and satellite-based environmental measurements, land-use information and simulations of airborne chemical movement -- to estimate the PM2.5 pollution levels within the participants' residential ZIP codes. The model was created by Zhenyu Zhang, a Johns Hopkins Medicine otolaryngology postdoctoral fellow.

The researchers found long-term airborne exposure to PM2.5 increases the risk of losing one's smell by nearly twice (a 1.6- to 1.7-fold increase). They believe this may occur because the location of the olfactory nerve -- which contains the sensory nerve fibers relating to the sense of smell -- places it directly in the path of inhaled PM2.5 materials.

"Based on this result, we feel that long-term exposure to high levels of PM2.5 represents a common risk factor for the loss of sense of smell, especially in vulnerable populations such as older people -- but also one that is potentially modifiable if sources of PM2.5 components can be better controlled," says Ramanathan.

Next, the researchers plan to study socioeconomic factors among patients with anosmia to determine if they impact the chances of exposure to PM2.5 air pollution. They also hope to evaluate other air pollution components that may contribute to loss of smell, such as ozone.

Ramanathan is available for interviews.

SIMPLE PROTOCOL CAN IMPROVE USE OF PROVEN MEDICINAL TREATMENT FOR OPIOID DEPENDENCE

Media Contact: Michel Morris, melben1@jhmi.edu

Unintentional overdoses are the leading cause of death for Americans under 50, with many people knowing at least one person who has struggled with drug dependence. In a recent study, Johns Hopkins Medicine researchers found that effective treatments for opioid addiction are underutilized and offer a potential solution to the problem -- increasing access to medical help through a quality improvement project.

The study, published May 18, 2021, in the Journal of Hospital Medicine, details how a team led by Ashish Thakrar, an addiction medicine fellow at the Johns Hopkins University School of Medicine, propose a simple, yet effective awareness and educational program. The protocol increases the use of evidence-based medication -- that is, therapeutic drugs shown by scientific evidence to be useful at treating opioid dependence. There are currently only three evidence-based medications to treat opioid dependence, and Thakrar says they are all underutilized. Thakrar's team focused on increasing the use of one of these drugs -- buprenorphine -- in patients admitted to The Johns Hopkins Hospital, many with substance use-related issues.

Buprenorphine is a drug approved by the U.S. Food and Drug Administration to treat opioid dependence. Experts say that buprenorphine -- which also is an opioid -- can be prescribed alone or as part of a comprehensive treatment plan that includes counseling and other behavioral therapies to provide patients with a whole-person approach.

"Changing practice is hard," Thakrar says. "There are dozens of well-conducted prospective and retrospective studies showing that buprenorphine works. It reduces mortality by 50%, reduces the rate at which patients use opioids, improves the patient's quality of life and helps retain patients in other kinds of medical and dependence care."

Before the project was implemented for the study, Thakrar says only 10% of eligible patients received approved medications for treating opioid dependence. After the project, discharge prescriptions more than doubled to 24%. Thakrar says the increase was due to the use of a one-page, easy-to-use protocol posted in common areas of the hospital; the presentation of the protocol at a conference with a successful patient case study; and the establishment of a novel, resident-led buprenorphine bridge team.

The bridge team consists of a group of residents and attendees who are legally permitted to prescribe buprenorphine prescriptions. This facilitates the use of the drug for treating opioid dependence -- because while any provider can administer it within a hospital, prescriptions require a special waiver from the federal Drug Enforcement Administration.

As part of the quality improvement project tested during the study, 140 internal medicine residents and 16 combined medicine-pediatrics residents received one hour of formal education about opioid use disorder. Additionally, 28 residents who were specializing in urban health primary care spent one month in a clinical rotation focused on dependence medicine. During that rotation, they completed the eight-hour training required to receive the DEA waiver. The training included guidance on selecting patients, shared decision-making around treatment, avoiding precipitated withdrawal, dosing buprenorphine and establishing follow-up.

After learning and implementing the protocol, the majority of residents reported feeling more comfortable and more knowledgeable using the buprenorphine treatment.

"Providers want to give good care to patients with opioid dependence, and are eager for tools that can help them do so," says Thakrar. "Many of the limitations for providing the best care are structural and logistical, so we need multidisciplinary approaches that include nurses and social workers. Collaboration is key."

Thakrar says the buprenorphine bridge team continues to be active at The Johns Hopkins Hospital. Since the team was established in 2019, the hospital also has started a full dependence medicine consult service.

"I hope that other hospitals can see that there are protocols that can improve the quality of care," Thakrar says. "Small changes can make a big difference for patients with opioid dependence."

Thakrar is available for interviews.

STUDY SHOWS HOSTILE WORK ENVIRONMENTS ARE GLOBAL HEARTACHE FOR CARDIOLOGISTS

Media Contact: Brian Waters, bwaters3@jhmi.edu

In a global survey of nearly 6,000 cardiologists conducted by Johns Hopkins Medicine and the American College of Cardiology, researchers found that as many as 44% of those polled report experiencing a hostile work environment (HWE) at some point in their careers. Based on this finding and others reported in a recent study assessing the survey responses, the researchers suggest that HWE -- characterized by emotional harassment, discrimination, sexual harassment or any combination of the three -- has an adverse effect on professional and patient interactions and relationships, raises concerns about the well-being of those impacted and may threaten the quality of patient care provided.

The study was published May 10, 2021, in the Journal of the American College of Cardiology.

"Unfortunately, we discovered that the problem of HWE is very widespread, with nearly half of the world's cardiologists experiencing some form of it at one time or another," says lead study author Garima Sharma, M.D., assistant professor of medicine at the Johns Hopkins University School of Medicine. "We found HWE in cardiology prevalent across regions, races and ethnicities, and both sexes and all gender identifications."

The 50-item survey in the study was given between September and October 2019 to 5,931 cardiologists in Africa, Asia, the Caribbean, Europe, the Middle East, Oceania, and North, Central and South America. Participants were queried about their demographics, practice environment, academic rank and experiences with discrimination and harassment. Seventy-seven percent of the respondents were men, 54% were white (followed by 17% Asians, 17% Hispanics and 3% Blacks), 73% were age 54 or older and 75% were married.

Cardiologists from the European Union made up the biggest block of respondents (32%), followed by cardiologists from South America (18%); the Middle East, Eastern Europe and Asia (all 9%); Africa (8%); North America (7%); Central America (6%) and Oceania (2%).

"Based on the responses from the survey, we found incidences of HWE were most commonly reported by women [68%], Blacks [53%] and North Americans [54%]," says Roger Blumenthal, M.D., director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease and professor of medicine at the Johns Hopkins University School of Medicine. "Gender was the most frequent cause of discrimination [44%], followed by age [37%], race [24%], religion [15%] and sexual orientation [5%]."

Seventy-five percent of survey respondents said HWE adversely affected professional activities with colleagues, while 53% reported a negative impact on relationships with their patients.

Looking at each subset of HWE studied, Sharma says that emotional harassment was experienced by nearly one-third of cardiologists, 30% reported at least one form of discrimination, and women endured more incidences of sexual harassment -- with 44% stating they had experienced multiple types.

"These data come at a crucial time when harassment and the culture of discrimination in medicine are being openly challenged," the study states. "These findings support the need to improve the culture within medicine greatly and raise a call to action to address harassment and discrimination."

Sharma and Blumenthal are available for interviews.

TO CULTURE OR NOT TO CULTURE: NEW TOOL HELPS DECIDE -- AND LOWER ANTIBIOTIC USE IN THE PICU

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

The dictionary defines stewardship as "the job of properly and responsibly taking care of things so that they can be used effectively." Nowhere is that concept -- and the responsibility attached to it -- taken more seriously than in a pediatric intensive care unit (PICU), especially when it involves stewarding the appropriate use of antibiotics. Now, Johns Hopkins Medicine researchers hope to make that high-value health care task simpler and more effective with a new bedside tool that helps clinicians better determine when to test for bacteria in endotracheal tubes being used for critically ill pediatric patients.

The findings were reported in the May 2021 issue of the journal Pediatrics.

To diagnose potentially serious bacterial respiratory infections in a PICU patient receiving invasive mechanical ventilation with an endotracheal tube, physicians and nurses often obtain secretions from inside the tube (known as an endotracheal aspirate) and culture it in the laboratory. The problem with these endotracheal aspirate cultures (EACs) is they may lead to a case of mistaken identity that could do the patient more harm than good, says study lead author Anna Sick-Samuels, M.D., M.P.H., a pediatric infectious disease specialist at Johns Hopkins Children's Center and assistant professor of pediatrics at the Johns Hopkins University School of Medicine.

"The human respiratory tract is far from a sterile environment, so bacteria cultured from aspirated samples may just be part of the body's normal microflora and not be causing an infection that needs antibiotics," says Sick-Samuels. "However, the detection of any bacteria in these cultures is often misinterpreted as a sign of a ventilator-associated infection, which then may result in unnecessary -- and potentially harmful -- antibiotic treatment."

To address the problem, Sick-Samuels and her colleagues developed a clinical decision support algorithm for use in the PICU. The algorithm is a simple flow chart of progressively more definitive, "yes or no" criteria by which clinicians can make an informed, rather than speculative, decision about whether or not an EAC is needed.

"The algorithm standardizes the thought process and makes the clinician carefully consider whether or not to call for an EAC, which in turn, prevents a 'knee-jerk' response to bacteria and the inappropriate use of antibiotics," says Sick-Samuels. "It also helps reduce the problem of clinicians ordering repeated EACs from the same patient, even though the same bacteria typically grow again in repeated cultures."

For a PICU patient with a tracheostomy (a surgically created airway directly into the trachea) or an endotracheal tube in place for more than 48 hours, Sick-Samuels explains that the algorithm asks clinicians to consider obtaining an EAC only if:

The patient has an increased quantity of secretions in the tracheostomy or endotracheal tube over time.

There is at least one additional supporting sign of infection, such as fever greater than 38 degrees Celsius (100.4 degrees Fahrenheit), an increase in white blood cell counts or a chest X-ray that indicates a developing pneumonia.

The patient has not had another EAC within the past 3 days.

To test the effectiveness of their algorithm, Sick-Samuels and her research team put it to work as part of a 12-month quality improvement program at the Children's Center PICU. In the year before the tool was implemented, the researchers documented 557 EACs obtained over 5,092 days of patients on mechanical ventilation (tracheostomy or endotracheal tube). This was equivalent to 10.9 EACs for every 100 ventilator-days.

In the year after the algorithm became part of the regular clinical practice at the Children's Center PICU, the number of EACs dropped to 234 over 3,654 ventilator-days, or 6.5 per 100 ventilator-days -- a 40% reduction. The researchers say the use of the algorithm and the resulting sustained decline in EACs did not change the number of deaths, readmissions or lengths of stay for patients in the PICU. They also estimate that the direct cost savings from obtaining fewer EACs would be approximately $26,000 per year.

What makes this stewardship different from other programs seeking to prevent the inappropriate use or overuse of antibiotics, says Sick-Samuels, is that the "decision tree" process goes to work earlier in the thought process before antibiotics might be started.

"The algorithm makes the early decision for or against microbiological testing the pivotal point, not the choice of whether or not to prescribe antibiotics," she says. "At JHCC, it really did make our staff more mindful and aware of their actions, and it led to a shift in practice that was sustained even through the COVID-19 pandemic."

Next, the researchers plan to introduce diagnostic stewardship of EACs at 15 pediatric centers across the United States, validate its effectiveness and show that the stewardship program can be adapted for use in other PICUs. They also hope their efforts will serve as a model for EAC decision-making tools that can be used in other clinical settings.

Sick-Samuels is available for interviews.

Credit: 
Johns Hopkins Medicine

Using a DNA-led framework to reunite separated migrant families

Nearly three years after the Trump administration's "Zero Tolerance" policy went into effect, more than 445 children remain separated from their families, largely due to insufficient identifying paperwork and U.S. immigration officials' failures to plan, track and reunite separated families. In a Policy Forum, Elizabeth Barnert and colleagues - an interdisciplinary group of physicians, scientists and human rights advocates - argue that a well-defined, replicable, scalable, and sustainable framework to collect and manage sensitive DNA data is urgently needed in order to play a part in helping reunite separated migrant families safely and ethically. "We recognize that no technology - including DNA analysis - is capable of reuniting all families; however, this inherent limitation cannot and should not serve as a rationale to avoid applying scientific tools to support the prompt reunification of parents and children whose whereabouts are unknown," write Barnert et al. The authors' call to action is particularly timely considering the upcoming release of the Biden Administration's Family Reunification Task Force's initial report, due on June 2, 2021. "Given the Biden Administration's executive order to reunite migrant children separated from their families by previous administrations, it is imperative that scientists and human rights advocates develop an international protocol that sets out guidelines and best practices for a DNA-led approach for family reunification," write the authors. While protocols and standards already exist for using DNA technology to identify the deceased, a global protocol for using DNA to reunite the living has yet to be established. Here, Barnert and colleagues provide an overview of how DNA-based strategies have been used in the past to identify the unknown and outline how a DNA-led framework for family reunifications could be established. They address scientific rigor, rights protection, ethical processes, trauma-informed protocols, and more.

Credit: 
American Association for the Advancement of Science (AAAS)

Technology that predicts protein stability is released by UK university spin-out company

image: QUBES takes a 'fingerprint' of protein fluorescence and converts it into a prediction of protein stability as well as monitoring for changes in protein structure. QUBES is a cloud-hosted software platform that can be used anywhere with an internet connection.

Image: 
Chris Pudney, University of Bath

A cutting-edge digital tool that will make it cheaper, safer and faster for pharmaceutical companies to predict protein stability - a vital step in the development of new medicines - is being rolled out by scientists from the UK's University of Bath through their spin-out company, BLOC Labs.

The tool, launched this week, will help researchers identify the most promising protein molecules for drug development. It has the potential to play an important role in the creation of monoclonal antibodies (mAbs). The market for these therapeutic antibodies is worth over £70 bn.

Monoclonal antibodies are a type of protein derived from natural antibodies and then refined and mass produced in the lab. They are steadily transforming the way we treat and prevent diseases, from cancer and conditions affecting the immune system to viral infections. The coronavirus pandemic has triggered particular interest in mAbs, as a number of protein candidates are showing great promise as therapies to treat Covid-19, and are currently being trialled in humans.

STABILITY IS KEY

Only mAbs that are known to be stable (that is, they neither break down easily nor clump together to form toxic compounds) are suitable for development, and finding a stable candidate adds massively to the cost and time of finding new drugs.

Until now, the process of determining protein stability has been a big headache for drug companies, with researchers testing vast libraries of molecules in their search for proteins with medicinal properties. However, the tool developed in Bath - called Quantitative Understanding of Bio-molecular Edge-Shift (QUBES) - is able predict the stability of proteins with startling speed and accuracy.

Dr Chris Pudney from the University's Department of Biology & Biochemistry and developer of QUBES, said: "We're really excited by the potential of QUBES because it can be used immediately in the biopharmaceutical industry in quality assurance, formulation and development."

He added: "Proteins are notoriously unstable for a good reason - the body wants to recycle them constantly. But with a therapeutic product, you need stability - if a protein breaks down and aggregates, it becomes toxic. Finding stable proteins is hugely expensive for pharmaceutical companies, but using our tool to find the best molecule possible will cut down on the time and cost of development massively."

QUBES FINGERPRINTING

QUBES works by allowing researchers to accurately 'fingerprint' a protein's structure and predict stability under nearly any condition of concentration or formulation. The technique uses fluorescence to map protein structure and then applies a mathematical algorithm, based on the position and type of the protein's atoms, to calculate stability. Thanks to an online suite of software - also developed in Bath - laboratories can interpret their fluorescent data from anywhere in the world, using equipment found in most biochemistry labs without modifications.

Elaborating on the fingerprinting technique, Dr Pudney said: "Proteins contains tryptophan - an amino acid that emits fluorescent light. Every protein molecule has a unique fluorescent signature, and QUBES leverages this optical phenomenon, applying mathematical techniques to analyse and interpret the fluorescence.

"The software suite takes this academic work and makes it incredibly easy for people to use. You can run it on any machine - even on your mobile phone. It's ultra-rapid and ultra-easy, and it offers an incredibly high level of security - in fact, we have a grade of security that's normally reserved for the financial service industry."

What sets QUBES apart from its competitors is the quality of its readings and its extreme flexibility. Dr Pudney explains: "Not only is our approach faster, more accurate and more sensitive than anything else on the market, but it can also predict stability at any concentration and in any formulation - unlike other tools on the market, which require set conditions."

Dr Pudney's team have recently conducted a validation study of the QUBES technology with the National Physical Laboratory (NPL) under the government backed 'Measurement for Recovery Scheme' scheme, which provides independent validation of technology by the country's leading analytical facility.

Dr Alex Jones, who led the study at NPL, said: "We tested the QUBES approach using a range of analytical methodologies and found that it tracks subtle changes in protein structure and stability with remarkable sensitivity when compared to established methodologies. The approach is fast and simple to implement."

Credit: 
University of Bath

Plastic waste has some economic benefit for developing countries

PULLMAN, Wash. - For decades, wealthy nations have transported plastic trash, and the environmental problems that go with it, to poorer countries, but researchers have found a potential bright side to this seemingly unequal trade: plastic waste may provide an economic boon for the lower-income countries.

In a study published in the Journal of World Systems Research, Yikang Bai of Washington State University and Jennifer Givens of Utah State University analyzed 11 years of data on the global plastics trade against economic measures for 85 countries. They found that the import of plastic waste was associated with growth in gross domestic product per capita in the lower-income countries.

"Our study offers a nuanced understanding of the global trade in plastic waste," said Bai, a recent WSU Ph.D. graduate and lead author on the study. "Media coverage often has a narrative that developed countries shift environmental harms to less developed countries. There's another layer of the story: plastic waste could be used as a resource first, even though ultimately it could still add to the environmental burdens of less-developed countries."

The authors emphasized that plastic waste is still a big problem, especially for developing countries, as most does not get recycled and even plastics that are recycled still ultimately end up negatively affecting the environment. This study only indicates that some plastic waste is being purchased and repurposed before being thrown away.

For the study, Bai and Givens analyzed data from the United Nations and the World Bank looking at several economic variables as well as trade information on common plastic wastes such as polyethylene and polystyrene, also known as #1 and #2 plastics respectively. They analyzed data on 45 high-income countries mostly found in the Global North, including European countries and the United States - and 40 lower income countries which are mostly found in the Global South such as Botswana, El Salvador and Vietnam.

The data ranged from 2003 to 2013, allowing the researchers to conduct a longitudinal analysis--showing change over time--which can reveal a strong connection among the measures. While they found an association between economic benefits and plastic waste imports in the lower income countries, for the high-income countries there was no association between importing waste and economic growth.

While the study did not assess exactly how the plastic waste was being used in the developing countries, the authors note that it is likely they are recycling some of the plastic for use in industry and manufacturing. There was also some evidence that the lower-income countries were trading the plastic waste among themselves regionally.

"Most plastic doesn't get recycled - that's important to keep in mind," said Givens, a USU assistant professor of sociology. "A lot of plastic waste ends up in landfills or in the environment, so maybe it's a silver-lining that importing plastic waste is associated with economic development in developing countries. At least they are recycling some of it and not using virgin materials because plastics are made from fossil fuel chemicals."

The researchers emphasized that there is a lot of complexity in global trading of plastic waste. In the future, they plan to investigate the regional trade among countries as well as changes in more recent years, especially in light of the fact that China stopped taking plastic waste imports in 2018.

Even with the economic benefits of importing plastic waste, reducing environmental harm from plastics would still likely require changes from both high-income countries and lower-income countries, especially high-income countries, said Bai.

"Some people might argue that developed countries need to create more ways to better process plastic waste domestically, instead of looking for other destinations for plastic waste overseas," he said. "The way we recycle plastic waste varies greatly across the United States. Some communities may do it well, but in others, there is still room for improvement. Producing and using less plastic would be another way to reduce environmental harms."

Credit: 
Washington State University