Culture

Study reveals birth defects caused by flame retardant

A new study from the University of Georgia has shown that exposure to a now-banned flame retardant can alter the genetic code in sperm, leading to major health defects in children of exposed parents.

Published recently in Scientific Reports, the study is the first to investigate how polybrominated biphenyl-153 (PBB153), the primary chemical component of the flame retardant FireMaster, impacts paternal reproduction.

In 1973, an estimated 6.5 million Michigan residents were exposed to PBB153 when FireMaster was accidentally sent to state grain mills where it made its way into the food supply. In the decades since, a range of health problems including skin discoloration, headache, dizziness, joint pain and even some cancers have been linked to the exposure.

More striking, the children of those who were exposed seemed to experience a host of health issues as well, including reports of hernia or buildup in the scrotum for newborn sons and a higher chance of stillbirth or miscarriage among adult daughters.

Yet, little work has been done to understand how the chemical exposure could have impacted genes passed from an exposed father, said study author Katherine Greeson.

"It is still a relatively new idea that a man's exposures prior to conception can impact the health of his children," said Greeson, an environmental health science doctoral student in Charles Easley's lab at UGA's College of Public Health and Regenerative Bioscience Center.

"Most studies where a toxic effect is observed in children look only to the mothers and the same has been true of studies conducted on PBB153," she said.

Greeson and a team of researchers from UGA and Emory University used a unique combination of observational and laboratory approaches to demonstrate how PBB153 acted on sperm cells.

"Typically, scientific studies are either epidemiological in nature and inherently observational or focus on bench science, but in this study, we did both," said Greeson.

This approach allowed the researchers to mimic the known blood exposure levels of PBB153 in a lab environment.

"We were uniquely able to recreate this effect using our previously characterized human stem cell model for spermatogenesis," she said, "which allowed us to study the mechanism that causes this effect in humans."

The team looked at the expression of different genes in their human spermatogenesis model after dosing with PBB153 and found marked alterations in gene expression between dosed and undosed cells, specifically at genes important to development, such as embryonic organ, limb, muscle, and nervous system development.

"PBB153 causes changes to the DNA in sperm in a way that changes how the genes are turned on and off," said Greeson. "PBB153 seems to turn on these genes in sperm which should be turned off," said Greeson, which may explain some of the endocrine-related health issues observed in the children of exposed parents.

Though the study used this model to directly replicate exposure to PBB153, Greeson says this approach could be used to better understand the impact of other environmental exposures on reproduction, including large-scale accidental exposures to toxic chemicals or everyday exposures.

"Hopefully this work will lead to more studies combining epidemiology and bench science in the future, which will tell us more about why we're seeing an effect from an environmental exposure in human populations and encourage experimental studies to more closely mimic human exposures," she said.

Credit: 
University of Georgia

Down to the bone: Understanding how bone-dissolving cells are generated

image: Role of the protein Cpeb4 in the generation of cells critical to bone maintenance.

Image: 
Tokyo University of Science

Chronic bone and joint diseases, such as osteoporosis and rheumatoid arthritis, affect millions of people worldwide, particularly the elderly, degrading their quality of life. An important factor in both of these diseases is the excessive activity of bone-dissolving cells called osteoclasts. Osteoclasts are formed through differentiation from a certain type of immune cell called macrophage, after which they acquire their new role in the maintenance of bones and joints: breaking down bone tissue to allow osteoblasts-another type of cell-to repair and remodel the skeletal system.

Broadly, two intracellular processes are involved in this differentiation: first, transcription-in which a messenger RNA (mRNA) is created from the genetic information in DNA-and then, translation-in which the information in the mRNA is decoded to produce proteins that perform specific functions in the cell. Since the discovery of the role of a particular protein called RANKL in osteoclast formation, scientists have solved a considerable portion of the puzzle of which cell signaling pathways and transcription networks regulate osteoclast generation. Yet, the post-transcription cellular processes involved remain to be understood.

Now, in a new study published in Biochemical and Biophysical Research Communications, scientists at Tokyo University of Science, Japan, unraveled the role of a protein called Cpeb4 in this complex process. Cpeb4 is part of the "cytoplasmic polyadenylation element binding (CPEB)" family of proteins, which bind to RNA and regulate translational activation and repression, as well as "alternative splicing" mechanisms that produce protein variants. Dr Tadayoshi Hayata, who led the study, explains: "CPEB proteins are implicated in various biological processes and diseases, such as autism, cancer, and red blood cell differentiation. However, their functions in osteoclast differentiation are not clearly known. Therefore, we conducted a series of experiments to characterize a protein from this family, Cpeb4, using cell cultures of mouse macrophages."

In the various cell culture experiments conducted, mouse macrophages were stimulated with RANKL to trigger osteoclast differentiation and the evolution of the culture was monitored. First, the scientists found that Cpeb4 gene expression, and consequently the amount of Cpeb4 protein, increased during osteoclast differentiation. Then, through immunofluorescence microscopy, they visualized the changes in the location of Cpeb4 within the cells. They found that Cpeb4 moves from the cytoplasm into nuclei, while presenting specific shapes (osteoclasts tend to fuse together and form cells with multiple nuclei). This indicates that the function of Cpeb4 associated with osteoclast differentiation is likely carried out inside the nuclei.

To understand how RANKL stimulation causes this Cpeb4 relocalization, the scientists selectively "inhibited" or represses some of the proteins that become involved "downstream" in the intracellular signaling pathways triggered by the stimulation. They identified two pathways as necessary for the process. Nonetheless, further experiments will be required to fully learn about the sequence of events that takes place and all the proteins involved.

Finally, Dr Hayata and his team demonstrated that Cpeb4 is absolutely necessary for osteoclast formation using macrophage cultures in which Cpeb4 was actively depleted. The cells in these cultures did not undergo further differentiation to become osteoclasts.

Taken together, the results are a stepping stone to understanding the cellular mechanisms involved in osteoclast formation. Dr Hayata remarks: "Our study sheds light on the important role of the RNA-binding protein Cpeb4 as a positive "influencer" of osteoclast differentiation. This gives us a better understanding of the pathological conditions of bone and joint diseases and may contribute to the development of therapeutic strategies for major diseases like osteoporosis and rheumatoid arthritis." Hopefully, the deeper level of understanding of osteoclast generation facilitated by this study will ultimately translate into improved quality of life for people living with painful bone and joint diseases.

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized
private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido.
Established in 1881, the university has continually contributed to Japan's development in science through
inculcating the love for science in researchers, technicians, and educators.

With a mission of "Creating science and technology for the harmonious development of nature, human beings, and
society", TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a
multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a
meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that
has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the
natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Associate Professor Tadayoshi Hayata from the Tokyo University of Science

Since 2018, Dr Tadayoshi Hayata has been Associate Professor and Principal Investigator at the Department of Molecular Pharmacology, Faculty of Pharmaceutical Science, at the Tokyo University of Science. His laboratory focuses on bone metabolism, cellular differentiation, molecular pharmacology, and similar fields to understand the nature of bone and joint diseases and find therapeutic targets. Dr Hayata is affiliated with several Japanese Societies and the American Society for Bone and Mineral Research. He has published over 50 original articles and given over 150 presentations at academic conferences. In addition, his research on osteoporosis has made it to Japanese newspapers several times.
https://www.tus.ac.jp/en/fac/p/index.php?7014

Journal

Biochemical and Biophysical Research Communications

DOI

10.1016/j.bbrc.2020.05.089

Credit: 
Tokyo University of Science

Phenothiazine derivatives may find use in photodynamic therapy

image: SEM images of the particles obtained by the nanoprecipitation of compounds 6 (a, b), 5 (c), and a 1 : 1 mixture of compounds 5 and 6 (d).

Image: 
Kazan Federal University

A group on organic compounds under Professor Ivan Stoikov's guidance has been working on phenothiazine derivatives at Kazan Federal University since 2016.

Probably the most well-known derivative among the general public is methylene blue - a dye with antiseptic properties.

According to co-author Alena Khadieva, recent studies also show its high potential for use as photochemical and photodynamic agent that can be applied in the incision area during surgical operations and for localized therapy of cancerous tumors. The main problem of using compounds similar in structure to methylene blue is their aggregation in aqueous media.

This paper is devoted to the preparation of new phenothiazine derivatives containing phenyl groups instead of alkyl groups, which, according to published data, will provide greater photochemical activity. The presence of phenyl groups should also provide steric hindrances to the dimerization of phenothiazine derivatives. It also leads to high absorption in the near-infrared spectrum. Near-infrared radiation is characterized by high penetration of biological tissues without damaging them. Photoactive antimicrobial, antibacterial and anti-cancer agents based on organic oligoaromatic and polyaromatic compounds are currently attracting increased attention of researchers, since this direction opens up prospects for overcoming antibiotic resistance.

The next objective of the study was to ensure high stability of the dispersions of new phenothiazine derivatives. For this, a binary associate was obtained in which the phenothiazine derivative containing carboxyl groups acts as an acid, and the deprotonated phenothiazine derivative as a base. Due to the presence of complementary groups, stable dispersions were obtained. The stability of the dispersions was confirmed by dynamic light scattering, and the composition of the associate - by ultraviolet spectroscopy. The particle morphology was also studied by scanning electron microscopy, which made it possible to establish that the formation of the associate also changes the shape of the particles.

The synthesis of new phenothiazine derivatives containing, along with phenyl groups, fragments capable of forming intermolecular hydrogen bonds and capable of forming stable dispersions in water, will significantly expand the scope of their application in the composition of materials for photodynamic therapy.

In addition to working to obtain more stable dispersions, as well as water-soluble phenothiazine derivatives for use in medicine, the group also plans to move further to creating phenothiazine-cyclophane associates for use as colorimetric test samples to determine the content of toxic ions. Some of the results were published in Synthesis of Tris-pillar [5] arene and Its Association with Phenothiazine Dye: Colorimetric Recognition of Anions.

Both inquiries under Dr. Vladimir Gorbachuk's supervision were financially supported by the Russian Science Foundation (Project No. 18-73-00293).

Due to the structural similarity of arylamine derivatives of phenothiazine with emeraldine (a popular conductive organic polymer), research for obtaining electrochemically active stable dispersions based on the emeraldine-phenothiazine associate is also seen as promising.

Credit: 
Kazan Federal University

COVID-19 loneliness linked to elevated psychiatric symptoms in older adults

Although social distancing is crucial in thwarting the spread of COVID-19, isolation and the ensuing loneliness may be severely detrimental for older adults. A new study conducted by researchers at Bar-Ilan University and the University of Haifa has linked COVID-19-based loneliness in older adults with elevated psychiatric symptoms of anxiety, depression, and trauma symptoms that immediately follow exposure to trauma. The findings were recently published in the American Journal of Geriatric Psychiatry.

The study focused on older adults, a sector of the population at greater risk for COVID-19 health complications that likely remained in stricter self-isolation than other age groups due to this risk. Notably, the researchers found that the effect of loneliness on psychiatric symptoms was most pronounced among participants who felt subjectively older than their chronological age. On the other hand, participants who felt subjectively younger than their chronological age exhibited no psychiatric symptoms related to loneliness.

"The way older adults perceive old age and their own aging may be more important to their coping and wellbeing than their chronological age," said Prof. Amit Shrira, from the Gerontology Program at the Interdisciplinary Department of Social Sciences at Bar-Ilan University, who conducted the study with Prof. Ehud Bodner and Dr. Yaakov Hoffman, of Bar-Ilan, and Prof. Yuval Palgi from the University of Haifa.

The findings may assist in identifying older adults at high risk for developing psychiatric symptoms due to COVID-19-related loneliness. In addition, they can guide the development of suitable interventions aimed at lowering perception of age in order to mitigate the negative impact of such loneliness and create a protective factor to prevent such a link. The data should also be helpful in advancing preparatory measures for a future pandemic.

What can be done to relieve the emotional burden of isolation among the elderly? Shrira, a clinical psychologist by training, recommends providing ongoing assistance and communication while adhering to relevant health guidelines. Regular conversations with family members, volunteers and even strangers can prevent the onset of deeper loneliness and the sense that no one is willing to hear their pain. Allowing them to share their experience and wisdom helps them feel more valuable. For those coping with feelings of boredom and emptiness during isolation, Shrira suggests that reading, listening to music, solving puzzles, cooking and baking, physical exercise (even the most minimal) and other leisure activities can refresh the normal, monotonous routine.

Credit: 
Bar-Ilan University

Study: National calorie menu labeling law will add years of healthy living, save billions

Correction: The headline on this news release has been changed to, "National calorie menu labeling law could add years of healthy living, save billions" from the original, "Study: National calorie menu labeling law will add years of healthy living, save billions."

BOSTON (June 9, 2020, 9:00 a.m. EDT)--The national law requiring chain restaurants to include calorie labels on menus is estimated to prevent tens of thousands of new heart disease and type 2 diabetes cases--and save thousands of lives--in just five years, according to a new study estimating the law's impact.

The research model also estimated that the law would produce $10-14 billion in healthcare cost savings and another $3-5 billion in societal cost savings, such as from prevented lost productivity, over a lifetime.

The study simulates what would happen if one million hypothetical Americans, aged 35-80, cut their calorie intake moderately while dining out, after making healthier choices based on the labels. The research, published in Circulation: Cardiovascular Quality and Outcomes, was led by researchers at the Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts University and the Harvard T.H. Chan School of Public Health.

The analysis estimated that beginning in 2018, when the law was implemented, until 2023, healthier consumer menu choices would:

Prevent 14,698 new cases of heart disease (including 1, 575 deaths)

Prevent 21,522 new type 2 diabetes cases

Add 8,749 years of life (in good health)

When calculated over a lifetime, the analysis estimated better consumer menu choices would:

Prevent 135,781 new heart disease cases (including 27,646 deaths)

Prevent 99,736 type 2 diabetes cases

Add 367,450 years of life (in good health)

"Prior to COVID-19, Americans were relying on restaurants for one in five calories, on average. Most likely, we will come to rely on them again. Our study shows that menu calorie labeling may prevent meaningful disease and save billions of dollars in healthcare costs," said Dariush Mozaffarian, dean of the Friedman School. Mozaffarian is co-first author of the study along with Junxiu Liu, a postdoctoral scholar at the Friedman School.

The simulation estimated, based on prior interventional studies of food labeling, that menu calorie labeling would lead consumers toward lower calorie choices, resulting in a modest 7 percent fewer calories eaten at any average restaurant meal. The researchers conservatively assumed that half of these "saved" calories from each restaurant meal would be offset by additional calories unconsciously consumed by the consumer elsewhere, for example, at home.

"We also found that menu calorie labeling could help reduce health disparities, with larger benefits among Hispanics and Blacks, those with lower income or education, and people with obesity," said Renata Micha, co-last author and associate research professor at the Friedman School.

In addition to consumer responses, the research team estimated the potential health and economic impacts if restaurants respond to the calorie labeling law by reformulating some of their items to reduce calorie contents. They found that the law's health benefits could be twice as large, compared to health effects from changes in consumer choices alone. To estimate the potential effects of restaurant reformulations, the team projected that at the end of five years, there would be an average 5 percent calorie reduction in restaurant meals. Once again, the researchers conservatively assumed that half of the "saved" calories from reformulated restaurant meals would be offset by additional calories consumed elsewhere.

"Our estimates were cautious, based on the idea that both consumers and restaurants would cut calories only modestly. Part of the attraction of eating out is pleasure, and our model assumes people will still treat themselves, but the experience can be healthier overall if both diners and the restaurant industry make changes," said co-last author Thomas Gaziano, of the Harvard Chan School and Brigham and Women's Hospital, who designed the simulation model used in the study.

The federal law and resulting FDA regulation requires restaurants that are part of a chain with 20 or more locations to post calorie information for menu items. The FDA has given covered restaurants temporary flexibility during the COVID-19 crisis, due to the pandemic's impact on the restaurant industry.

"Current flexibility is appropriate when so many Americans are unemployed, and schools are closed. But improving the healthfulness of our food system is crucial, given the pandemic's disproportionate impact on people with diet-related conditions like diabetes and obesity, and further links to health disparities," Mozaffarian said.

"We need to change our food system through equitable, efficient and sustained food and nutrition policies. Food labeling is an effective tool to support informed consumer choice and stimulate industry reformulation," Micha said.

Methodology

The researchers used the Harvard CVD-PREDICT, a validated microsimulation model, and a simulated nationally representative sample of adults from four cycles of the National Health and Nutrition Survey (NHANES 2009-2016). Calorie intake was derived using up to two 24-hour recalls per person, with calorie intake from restaurants estimated by the reported source of food. Each simulated person was followed for 28 years on average, until death or age 100, whichever came first.

The authors caution that modeling results do not provide proof of the menu calorie labeling law's health and cost impacts. In addition, the study was conducted before the emergence of SARS-CoV-2 and does not include the impact of the pandemic on consumer habits and the restaurant industry.

Credit: 
Tufts University, Health Sciences Campus

Novel DNA analysis will help to identify food origin and counterfeit food in the future

image: Kairi Raime, the lead author of the article.

Image: 
Kairi Raime

Estonian scientists are developing a DNA-based method of analysis that enables them to identify food components and specify the origin of a foodstuff.

Bioinformatics specialists at the University of Tartu, in cooperation with the Competence Centre on Health Technologies, have published a research paper in the journal Frontiers in Plant Science in which they indicated the possibility to identify components in thermally processed food using DNA analysis even if the quantities were very small. The scientists analysed thermally processed cookies that contained a small amount of lupin flour. The DNA analysis provided reliable identification of lupin even when the lupin flour content in the dough was just 0.02%.

Food always contains the DNA traces of the plants, animals and microorganisms that have been used or that the food or its raw materials have come into contact with in the production process. DNA analysis can provide valuable information on the content, origin, safety and health benefits of food and will make the identification of counterfeit foods and non-compliances in the ingredients specified on the packaging more reliable in the future. For example, certain cases gained attention last year in which the origin of honey and the authenticity of Estonian honey needed verification. The novel DNA analysis would make it possible to solve such issues.

According to Kairi Raime, the lead author of the article, Research Fellow of Bioinformatics at the Institute of Molecular and Cell Biology and a doctoral student at the University of Tartu, their method is a major step forward in the development of DNA-based methods for food analysis. "Our method helps to identify the actual biological contents and origins of food via DNA information and thus ensures the safety and authenticity of the food," she explained. Raime is planning to defend her PhD dissertation on the topic.

The DNA may be significantly degraded in processed food. Scientists extracted DNA from the cookies and analysed it using DNA sequencing technology. For the analysis of a single biscuit, approximately 20 million DNA sequences were obtained. Based on these, and by using bioinformatic analysis, it was possible to specify the DNA of the species found in the sample analysed. The main issue was the preparation of the DNA for sequencing, as the DNA is often degraded in food and even minute amounts of DNA molecules must be identified.

Kaarel Krjutškov, Head of the Precision Medicine Laboratory of the Competence Centre on Health Technologies and Senior Research Fellow of Molecular Medicine at the University of Tartu, whose laboratory was used to prepare the sequencing of the DNA extracted from the biscuits, noted that faking the DNA fingerprint of a food is complicated and expensive, and it is therefore cheaper to offer authentic food. "People can see that in medicine, precise DNA analysis is already a reality, but in food industry and in the field of food safety, the golden age of DNA-based analysis is yet to come," Krjutškov remarked.

The research used a method based on short, unique DNA sequences (k-mers) for analysing genomic DNA data, which enables the scientists to quickly identify plant or bacterial DNA present in a food or an environmental sample. The Chair of Bioinformatics at the Institute of Molecular and Cell Biology at the University of Tartu has been developing competence in the bioinformatics of k-mers and DNA analysis over the last five years. The software developed in the Chair of Bioinformatics has been used both in medicine and for providing food safety.

The article authors' earlier cooperation resulted in the NIPTIFY foetal chromosomal disorder test, which helps to detect, with almost 100% accuracy, the DNA sequences causing foetal Down syndrome in the mother's blood sample as early as the tenth week of pregnancy. The genome analysis method developed in the Chair of Bioinformatics is used to identify pathogenic bacteria, specify their disease-causing capabilities and predict antibiotic resistance. This enabled Maido Remm, Professor of Bioinformatics at the University of Tartu, and his working group to advise the management board of a production company contaminated with a dangerous strain and to help determine the spread of type ST1247 in the company during the listeria outbreak in autumn 2019.

According to Remm, the research article proves that DNA sequencing can also be used for identifying allergenic ingredients in processed food. "DNA sequencing is a promising diagnostic method which makes it possible to quickly obtain precise information about food and the microbes around us," he said. "The use of sequencing and k-mers makes it possible in a very short time to implement a diverse range of diagnostic tests that meet the needs of researchers and companies."

Credit: 
Estonian Research Council

Study identifies network of genes that directs trachea and oesophagus development

A new study reporting how a network of genes directs the development of the trachea and oesophagus in mice has been published today in eLife.

The results provide new insight on the genes present during development that enable the formation of the trachea and oesophagus, more commonly known as the windpipe and food pipe, respectively. This may help scientists understand what causes birth defects in which the two structures do not fully separate, leading to eating and breathing difficulties. The findings may also help scientists one day grow oesophagus or trachea tissue in the lab to treat such birth defects or conditions such as cancer that may destroy these tissues.

During prenatal development, a tube of stem cells in the embryo gives rise to the cells of both the oesophagus and trachea. These cells become distinct and eventually the two structures separate. Previous studies have suggested that a pair of master gene regulators called NKX2.1 and SOX2 may control this process, but it is not clear which genes are activated by these regulators or if there are other regulators that might also be involved.

"We wanted to determine all of the genes that distinguish the trachea from the oesophagus and to learn how NKX2.1 and SOX2 influence the development of these organs," says lead author Akela Kuwahara, a Developmental & Stem Cell Biology Program graduate at the University of California, San Francisco (UCSF), US.

To do this, Kuwahara and a team of researchers led by Jeffrey Bush, Associate Professor at the Department of Cell & Tissue Biology, UCSF, used single cell RNA sequencing to compare all the genes that were switched on in the cells of the developing oesophagus and trachea in mice. Their results showed there are two very different sets of genes that are turned on during early development of the two organs.

Next, they compared which genes were turned on in the oesophagus and trachea of developing mice, comparing animals that had a functional NKX2.1 gene with those that did not. Most of the genes needed for the two tissues to develop were still turned on in the mice lacking NKX2.1. But a few important genes were different in these animals, including for example those needed to grow the cartilage that supports the trachea or the smooth muscle that moves food down the oesophagus.

"This suggests that NKX2.1 is not the master regulator for all genes involved in trachea development, but instead regulates only a small number of important genes," Kuwahara explains. "Our results reveal multiple new genes that are essential for trachea and oesophagus development in mice, but we now need to determine if these same genes are involved in the development of these organs in humans."

"Learning more about these genes and whether they play similar roles in humans is key to understanding how defects of the trachea and oesophagus can occur at birth," adds senior author Jeffrey Bush. "In the longer term, this insight may help us discover ways to grow new tissue from stem cells to help counter these defects."

Credit: 
eLife

Armor on butterfly wings protects against heavy rain

ITHACA, N.Y. - An analysis of high-speed raindrops hitting biological surfaces such as feathers, plant leaves and insect wings reveals how these highly water-repelling veneers reduce the water's impact.

Micro-bumps and a nanoscale wax layer on fragile butterfly wings shatter and spread raindrops to minimize damage.

The study, "How a Raindrop Gets Shattered on Biological Surfaces," published June 8 in the Proceedings of the National Academy of Sciences.

The research showed how microscale bumps, combined with a nanoscale layer of wax, shatter and spread these drops to protect fragile surfaces from physical damage and hypothermia risk.

There already exists a large market for products that use examples from nature - known as biomimicry - in their design: self-cleaning water-resistant sprays for clothes and shoes, and de-icing coatings on airplane wings. Findings from this study could lead to more such products in the future.

"This is the first study to understand how high-speed raindrops impact these natural hydrophobic surfaces," said senior author Sunghwan "Sunny" Jung, associate professor of biological and environmental engineering in the College of Agriculture and Life Sciences. The lead author is Seungho Kim, a postdoctoral researcher in Jung's lab.

Previous studies have looked at water hitting insects and plants at low impacts and have noted the liquid's cleaning properties. But in nature, raindrops can fall at rates of up to 10 meters per second, so this research examined how raindrops falling at high speeds interact with super-hydrophobic natural surfaces.

Raindrops pose risks, Jung said, because their impact could damage fragile butterfly wings, for example.

"[Getting hit with] raindrops is the most dangerous event for this kind of small animal," he said, noting the relative weight of a raindrop hitting a butterfly wing would be analogous to a bowling ball falling from the sky on a human.

In the study, the researchers collected samples of leaves, feathers and insects. The latter were acquired from the Cornell University Insect Collection, with the help of co-author Jason Dombroskie, collection manager and director of the Insect Diagnostic Lab.

The researchers placed the samples on a table and released water drops from heights of about two meters, while recording the impact at a few thousand frames per second with a high-speed camera.

In analyzing the film, they found that when a drop hits the surface, it ripples and spreads. A nanoscale wax layer repels the water, while larger microscale bumps on the surface creates holes in the spreading raindrop.

"Consider the micro-bumps as needles," Jung said. If one dropped a balloon onto these needles, he said, "then this balloon would break into smaller pieces. So the same thing happens as the raindrop hits and spreads."

This shattering action reduces the amount of time the drop is in contact with the surface, which limits momentum and lowers the impact force on a delicate wing or leaf. It also reduces heat transfer from a cold drop. This is important because the muscles of an insect wing, for example, need to be warm enough to fly.

"If they have a longer time in contact with the cold raindrop, they're going to lose a lot of heat and they cannot fly very easily," Jung said, making them vulnerable to predators, for example.

Repelling water as quickly as possible also is important because water is very heavy, making flight in insects and birds difficult and weighing down plant leaves.

"By having these two-tiered structures," Jung said, "[these organisms] can have a super hydrophobic surface."

Credit: 
Cornell University

Heat and humidity battle sunshine for influence over the spread of COVID-19, research

An international team of researchers led by McMaster University has found that while higher heat and humidity can slow the spread of COVID-19, longer hours of sunlight are associated with a higher incidence of the disease, in a sign that sunny days can tempt more people out even if this means a higher risk of infection.

The findings, published online the journal Geographical Analysis, inform the widespread scientific debate over how seasonal changes, specifically warmer weather, might shape the spread of COVID-19.

While research has shown that pathogens such as influenza and SARS thrive in lower temperatures and humidity, little is known about SARS-CoV2, the agent that causes COVID-19.

"There is a lot of pressure to reopen the economy, and many people want to know if it will be safer to do so in the summer months," says Antonio Páez, a professor and researcher in McMaster's School of Geography & Earth Sciences who is lead author of the study.

"Restrictions in movement, which have begun to ease around the world, hinge in part on how SARS-CoV2 will be affected by a change in season," he says.

Páez and colleagues from Spain's Universidad Politecnica de Cartegena and Brazil's Universidade Federal de Pernambuco investigated climate factors in the spread of COVID-19 in several provinces in Spain, one of the countries hardest hit by the pandemic, with more than 270,000 cases.

They combined and analyzed data on reported cases of the disease and meteorological information over a period of 30 days that began immediately before a state-of-emergency was declared.

At higher levels of heat and humidity, researchers found that for every percentage increase, there was a 3 per cent decline in the incidence of COVID-19, possibly because warmer temperatures curtail the viability of the virus.

The opposite was true for hours of sunshine: more sun meant greater spread. The researchers speculate the increase may be related to human behaviour, since compliance with lockdown measures breaks down in sunnier days.

They were also surprised to find rates of transmission dropped among more dense populations and in areas with more older adults, suggesting those populations regard themselves as being at greater risk, and so are more likely to adhere to lockdown guidance.

While older adults are more vulnerable to the disease, researchers believe they are less likely overall to contribute to the spread of the disease because they are more apt to be isolated from others because of health or mobility issues.

Páez stresses that models such as the one he helped develop show that contagion of COVID-19 declines as a lockdown progresses, possibly to the vanishing point - an argument for maintaining discipline despite the approach of pleasant weather.

"We will likely see a decrease in the incidence of COVID-19 as the weather warms up, which is an argument for relaxing social distancing to take advantage of the lower incidence associated with higher temperatures" he says. "But a more conservative approach would be to use the months of summer to continue to follow strict orders to remain in place and to crush this pandemic."

Credit: 
McMaster University

Botox is an effective treatment for some common sports injuries, new research suggests

June 9, 2020 - While botulinum toxin is commonly known as a cosmetic treatment for facial lines and wrinkles, a growing body of evidence suggests that "Botox" can also be an effective treatment for certain sports injuries and chronic pain conditions, according to a review in the June issue of Current Sports Medicine Reports, official journal of the American College of Sports Medicine (ACSM). The journal is published in the Lippincott portfolio by Wolters Kluwer.

Clint Moore, DO, and colleagues of the Uniformed Services University of the Health Sciences assembled and analyzed previous research on the use of botulinum toxin A (BoNT-A) - best known by the brand name Botox - for treatment of musculoskeletal disorders. "We found evidence showing promising pain relief and functional improvements using botulinum toxin for some very common conditions, including plantar fasciopathy, tennis elbow, and painful knee osteoarthritis," Dr. Moore comments.

For These Musculoskeletal Disorders, Evidence Supports Botulinum Toxin Injection

Various types of BoNT-A are available, but all act on motor neurons (nerve cells) to produce muscle weakness and on sensory neurons to inhibit the release of pain modulators. As in cosmetic procedures, the effects of BoNT-A injection are time-limited, and treatment may need to be repeated for sustained benefits. The effects on muscle contraction last about three months, while effects on pain may last for six months.

In a critical analysis of the research literature, Dr. Moore and colleagues identified studies showing that the neuromuscular blockade provided by BoNT-A can reduce pain and improve function in several musculoskeletal conditions:

Plantar fasciopathy: The most common cause of plantar heel pain, caused by thickening and other changes in the fibrous plantar fascia in the foot. Several studies report that BoNT injections can be effective if initial conservative treatments are unsuccessful. Although limited, high-quality evidence suggests reduced pain and improved function after BoNT therapy, with no significant side effects.

Osteoarthritis: A very common and disabling condition causing pain and reduced function of the knee, shoulder, or other joints. Especially in the knee, studies have reported reduced pain and disability scores after intra-articular (into the joint) injections of BoNT-A. Dr. Moore and colleagues have found improvements lasting four to six months after BoNT injection for knee osteoarthritis.

Lateral epicondylitis: Often called "tennis elbow," a common cause of elbow pain. Studies have reported reduced pain and improvement in daily activities after BoNT-A injection. In some reports, reductions in finger movement and grip strength have occurred due to the (temporary) motor effects of BoNT-A.

Chronic exertional compartment syndrome: A condition causing painful and potentially damaging increases in pressure in muscle compartments, usually after exercise. Based on limited evidence, BoNT-A injections may be a safe and effective treatment, in some cases avoiding the need for surgery.

For each of these conditions, Dr. Moore and colleagues discuss the role of BoNT-A and how they use it in their practice, including injection technique and dosage. Their paper also reviews studies using BoNT-A for patients with myofascial pain syndrome, a relatively common cause of chronic pain - with inconclusive results.

The authors note that all of these are "off-label" uses for which BoNT-A is not an FDA-approved treatment, and emphasize the need for appropriate patient selection and counseling. Dr. Moore and coauthors conclude, "Further research is required to provide stronger clinical recommendations for the use of BoNT in musculoskeletal conditions."

Credit: 
Wolters Kluwer Health

Use of cystatin C for precise assessment of kidney function and cardiovascular risk

The glomerular filtration rate (GFR) is normally specified as a measure of kidney function. The GFR is the volume of blood that the kidneys filter per minute (the unit of measurement, in relation to a standardized body surface area, is therefore ml/min/1.73 m2). To calculate or estimate GFR (eGFR= estimated GFR), an equation based, inter alia, on the laboratory parameter serum creatinine is mostly applied. Creatinine, a non-protein nitrogenous substance, is a breakdown product of muscle metabolism that is released continuously and excreted in urine (making it a urinary substance). If kidney function is impaired, eGFR decreases and serum creatinine increases. However, because the body's own creatinine production depends on various factors (e.g. age, gender and muscle mass), the significance of creatinine-based eGFR (eGFRcr) is a recurrent topic of discussion among specialists. For example, the kidney function of a delicate elderly lady (with low muscle mass and correspondingly lower serum creatinine) may be wrongly assessed as normal, based on her creatinine level, even though her kidney function may be significantly reduced. Conversely, the muscular creatinine production in a bodybuilder may cause elevated serum creatinine values and thus lead arithmetically to a low eGFR (despite normal kidney function). The endogenous protein Cystatin C (Cys-C), which is permanently released in the metabolism of almost all body cells, therefore appears to be more suitable as a marker than serum creatinine. The volume of Cys-C amount is independent of age, gender and muscle mass - potential confounding factors in cystatin-based eGFR estimation (eGFRcys) are inflammation, cancer, thyroid dysfunction or steroid therapy. Cys-C measurement is also more expensive than creatinine, and the test is not available in every laboratory.

An equation for estimating eGFR that includes both parameters (eGFRcr-cys) has been shown to provide the most accurate approximation of true GFR, not only in early stages, but also in late stages of kidney disease. This may be due to the fact that the confounding factors of the two parameters are independent of each other and play a less significant role in the combined equation eGFRcr-cys, according to the authors. eGFRcr-cys is particularly suitable, therefore, when it is important to know how well kidneys function as precisely as possible and at an early stage (e.g. to calculate the dosage of certain drugs, for enrolment in studies, or in the case of potential kidney donors).

"Accurate measurement is needed for the early detection of CKD. The ERA-EDTA recommends that eGFRcys and eGFRcr-cys be implemented as the new standard", emphasizes Professor Denis Fouque, Lyon/France, NDT´s Editor-in-chief.

Restriction of kidney function is known to worsen the prognosis of patients with cardiovascular disease. "eGFRcys and eGFRcr-cys could be used in anybody with an eGFRcr of 45-60 or 60-90 ml/min/1.73 m2 plus another cardiovascular risk factor to confirm diagnosis/staging of CKD. The lowest identified eGFR should be used for forward planning", explains corresponding author, Dr. Jennifer Lees, Glasgow. "EGFRcys should be used in parallel with traditional cardiovascular risk factors in order to produce a more exact prediction of individual risk and to optimize the primary prevention cardiovascular disease."

Credit: 
ERA – European Renal Association

Computer modelling predicts where vaccines are needed most

Researchers have developed a model that can estimate regional disease burden and the impact of vaccination, even in the absence of robust surveillance data, a study in eLife reveals.

The report, originally published on May 26, highlights areas that would have the greatest benefit from initiating a vaccination programme against the virus, Japanese encephalitis (JE). This will in turn guide rational assessment of the cost and benefit of vaccinations, and support policymaker decisions on allocating vaccines.

JE is a viral infection of the brain transmitted by mosquitoes. It is endemic in Asia-Pacific countries, with three billion people at risk of infection according to the World Health Organization (WHO). Only a small number of infections are symptomatic (ranging from one in 25 to one in 1,000), but people with symptomatic infections have a high risk of death (around one in three of those infected). Those who survive are often left with considerable neurological and psychological symptoms.

There are a number of vaccines available for JE, but in 2013, WHO prequalification was given to a new JE vaccine that requires only a single dose, is cheap to produce and is safer than previous vaccines. This led to a great increase in vaccination in Asia. However, given the disease's widespread prevalence across several countries, it has not been possible to estimate the impact of these vaccinations on disease burden.

"Vaccination is the most effective method of prevention but it is difficult to decide where it should be implemented or to estimate the quantitative impact without good-quality surveillance data from before and after vaccination," says lead author Tran Minh Quan, who was a Research Assistant at the Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Vietnam, at the time of the study, and is now a graduate student at the University of Notre Dame, Indiana, US. "We developed a new approach using a modelling method that overcomes some of the limitations of sparse and variable surveillance data."

The team took a two-step approach to their analysis. First, they reviewed the available data on cases of JE and grouped this data by age. By focusing on age, this took out other variables and allowed the team to analyse the data according to a simple rule: the higher the rate of infection, the earlier in life people will acquire the infection. Then, by using a model that calculates the rate of infection using the age-grouped data, they generated a value called Force of Infection (FOI). This gives an idea of the intensity of transmission within a particular region.

In the second step, they used this FOI value to generate the disease burden in a specific region. When they ran this analysis with and without data on vaccination programs, it provided an estimate on the impact of vaccination on the number of global JE cases to date.

From this analysis, the team estimated that between 2000 and 2015, there were nearly two million cases of JE worldwide (1,976,238). Without vaccination, this number would have been 2,284,012 meaning that more than 300,000 JE cases were prevented globally because of vaccination. China had the highest burden of the disease but also benefited from the greatest impact of vaccination. On the other hand, estimates for countries including India, Vietnam and Indonesia suggested that up until 2015 these countries had high transmission intensity and that vaccination could be scaled up or introduced in these areas.

"Poor clinical outcomes and lack of a specific treatment makes JE prevention a priority," says senior author Hannah Clapham, who was a Mathematical Epidemiologist at the Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Vietnam, at the time the study was carried out, and is now Assistant Professor at NUS Saw Swee Hock School of Public Health, Singapore.

"We estimated that in 2015 there were still 100,000 cases of JE in Asia each year, meaning that two-thirds of all cases of this severe but vaccine-preventable disease were not being averted. Given there is a cheap vaccine now available, our results will help to identify the regions that would be best targeted for vaccination in future."

Credit: 
eLife

Pitt researchers' new material allows for unprecedented imaging deeper in tissues

PITTSBURGH -- A team from the Department of Chemistry has established an approach for the creation of a metal-organic framework material that provides new perspectives for the sensitization of near-infrared luminescent lanthanide ions, including unprecedented possibilities of imaging deeper in tissues for more comprehensive studies of biological systems with light.

Professor Nathaniel Rosi and his team worked with Professor Stephane Petoud, INSERM Research Director for the Center for Molecular Biophysics in France and Adjunct Professor in the Department of Chemistry on the paper, "Ship-in-a-bottle preparation of long wavelength molecular antennae in lanthanide metal-organic frameworks for biological imaging."

The research details the process in which small molecular precursors are loaded into the rigid three-dimensional cavities within lanthanide metal-organic frameworks, where they combine to form a dense array of extended molecular systems that work as an "antennae" that sensitize the lanthanide cations with long wavelengths excitation light. Those long wavelengths activate the near infrared emitting properties of the lanthanide, which may help to create images of areas located more deeply within biological systems.

Rosi also noted the luminescence from lanthanides lasts longer than background radiation in standard biological images, so researchers will have a time advantage when studying lanthanide samples.

"We've achieved a system that's sufficiently bright, that we can see using biological imaging in the near infrared. We can also excite it at long wavelengths, up to 600 nanometers which is highly desired so as not to disturb the biological systems." said Rosi.

The paper published in April in the Journal of the American Chemical Society.

Rosi said this novel optical imaging agent will also help researchers detect greater numbers of biological targets from a single experiment than what is possible with current methods.

"Current limitations in imaging allow one to only detect 4 maybe 5 molecules at best in a single imaging experiment. What if we wanted to detect five or six, or 10? There are 14 lanthanide elements across the periodic table. Most of them have very distinct, sharp, luminescent signals. We can potentially make up to 10 optical imaging probes with different lanthanides and be able to detect all of them because they don't have overlapping signals."

Credit: 
University of Pittsburgh

Lab makes 4D printing more practical

image: Shapeshifting materials produced at Rice University with a 3D printer morph from their original form to an alternate through changes in temperature, electric current or stress. This example shows how one printed configuration can be programmed to take various shapes.

Image: 
Verduzco Laboratory/Rice University

HOUSTON - (June 9, 2020) - Soft robots and biomedical implants that reconfigure themselves upon demand are closer to reality with a new way to print shapeshifting materials.

Rafael Verduzco and graduate student Morgan Barnes of Rice's Brown School of Engineering developed a method to print objects that can be manipulated to take on alternate forms when exposed to changes in temperature, electric current or stress.

The researchers think of this as reactive 4D printing. Their work appears in the American Chemical Society journal ACS Applied Materials and Interfaces.

They first reported their ability to make morphing structures in a mold in 2018. But using the same chemistry for 3D printing limited structures to shapes that sat in the same plane. That meant no bumps or other complex curvatures could be programmed as the alternate shape.

Overcoming that limitation to decouple the printing process from shaping is a significant step toward more useful materials, Verduzco said.

"These materials, once fabricated, will change shape autonomously," Verduzco said. "We needed a method to control and define this shape change. Our simple idea was to use multiple reactions in sequence to print the material and then dictate how it would change shape. Rather than trying to do this all in one step, our approach gives more flexibility in controlling the initial and final shapes and also allows us to print complex structures."

The lab's challenge was to create a liquid crystal polymer "ink" that incorporates mutually exclusive sets of chemical links between molecules. One establishes the original printed shape, and the other can be set by physically manipulating the printed-and-dried material. Curing the alternate form under ultraviolet light locks in those links.

Once the two programmed forms are set, the material can then morph back and forth when, for instance, it's heated or cooled.

The researchers had to find a polymer mix that could be printed in a catalyst bath and still hold its original programmed shape.

"There were a lot of parameters we had to optimize -- from the solvents and catalyst used, to degree of swelling, and ink formula -- to allow the ink to solidify rapidly enough to print while not inhibiting the desired final shape actuation," Barnes said.

One remaining limitation of the process is the ability to print unsupported structures, like columns. To do so would require a solution that gels just enough to support itself during printing, she said. Gaining that ability will allow researchers to print far more complex combinations of shapes.

"Future work will further optimize the printing formula and use scaffold-assisted printing techniques to create actuators that transition between two different complex shapes," Barnes said. "This opens the door to printing soft robotics that could swim like a jellyfish, jump like a cricket or transport liquids like the heart."

Credit: 
Rice University

Infected insects may warn of impending citrus disease a year in advance

image: Despite the first appearance of citrus greening disease in Florida in 2005, the bacterium wasn't found in Texas until 2011, when scientists detected it in the psyllids. The disease was not detected in citrus years until 2012, suggesting that psyllids may actually be used for early detection of the HLB pathogen in newly invaded areas.

Image: 
Plant Disease

Citrus greening disease (Huanglongbing of HLB), transmitted by the Asian citrus psyllid, is currently the biggest threat to the citrus industry and is threat to many parts of the world, including Asia, Africa, South America, and the Unites States. In Florida alone, citrus greening disease has accounted for losses of several billions of U.S. dollars.

Despite HLB's widespread prevalence, factors influencing the epidemic are poorly understood because most research has been conducted after the pathogen has been introduced. In an attempt to change this, several Texas-based scientists surveyed commercial and residential citrus trees from 2007 to 2017 and monitored the time-course variations in the proportion of citrus trees and the Asian citrus psyllid (ACP).

"Unlike previous studies on citrus greening disease epidemics that were typically initiated in commercial orchards after the disease had been introduced or became widespread in the area, our study commenced 5-years prior to the first detection of the greening bacterium in Texas and continued for 5 additional years," said Olufemi Alabi, one of the scientists involved in this research. "This gave us unique opportunity to obtain a holistic picture of the progression of the disease epidemics from its onset in both commercial and residential ecologies.

Despite the first appearance of citrus greening disease in Florida in 2005, the bacterium wasn't found in Texas until 2011, when scientists detected it in the psyllids. The disease was not detected in citrus years until 2012, suggesting that psyllids may actually be used for early detection of the HLB pathogen in newly invaded areas.

Over the course of this decade-long study, the proportion of infected trees and psyllids increased exponentially over time while the number of fields and residential backyards with at least one disease-affected citrus tree reached 26% and 40% respectively by 2017. Research also revealed seasonal fluctuations and will provide comprehensive insight into the ongoing citrus greening epidemic in Texas, with potential lessons for California and other citrus-growing regions that have not yet been affected.

"Our study suggest that a flatter progression of citrus greening disease epidemics could be achieved through the implementation of strategies to protect new plantings from infection and the continued implementation of the area-wide ACP management program," said Mamoudou Sétamou, the lead author of the article .

This study is good news for Texas farmers, who were alarmed by the rapid spread of citrus greening disease epidemics in Florida and worried that the smaller Texas citrus industry would be quickly overwhelmed once the disease appeared.

"Surprisingly, our research showed that although an exponential growth was observed in progression of infected trees in Texas, the annual rate of increase was relatively slower than reported from Florida. This led us to conduct series of analyses that enabled us to identify potential climatic and cultural factors that may be contributing to the relatively slow spread of citrus greening disease in Texas."

Credit: 
American Phytopathological Society