Brain

NRL researchers evaluate ultraviolet sources, combat COVID-19

image: Brett Huhman, U.S. Naval Research Laboratory senior research engineer, communicates with other team members over video chat during testing pulsed Xenon gas lamp source in support of COVID-19 at Washington, D.C. May 8, 2020. Huhman has been sending data to six other NRL researchers who have been teleworking to assess ultraviolet light sources applications against COVID-19 for Navy and Marine environments.

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U.S. Navy photo by Jonathan Steffen

WASHINGTON - U.S. Naval Research Laboratory researchers evaluated commercial ultraviolet (UV) sources for viral disinfection to combat COVID-19 on land and at sea, and established a dedicated UV characterization lab in five days to ensure safe introduction and effective operation of UV sources across the Fleet.

The Navy is investigating UV-C band (UVC) light as a potential disinfection technique for niche applications against COVID-19 for materiel going onto a ship, for common use areas on a ship, and general room disinfection on ships or shore facilities.

In a short period of time Brett Huhman, in NRL's Plasma Physics Division, reconfigured a laboratory space, conferred with subject matter experts across the NRL Materials Science and Component Technology directorate, and borrowed needed equipment to establish a UV characterization laboratory.

"Testing at NRL includes UV unit longevity and reliability, identifying easy-to-use dosimeters, reflections from shipboard surfaces, and secondary ozone generation from these UV systems," Huhman said. "Scientists at other Navy labs are using NRL data to help them test efficacy against viral loads on Navy and Marine relevant surfaces, such as bare metal tools and painted metal surfaces, and cardboard boxes."

There are numerous companies offering products that produce UV light and are designed for a variety of small and large-scale applications. The Naval Sea Systems Command (NAVSEA) requested NRL scientists to study and characterize the energy density, UV spectrum, and reliability of commercially available units.

"As the Navy wishes to quickly evaluate the efficacy of these commercial sources before procurement, a small investment was deemed necessary, in order to help the Navy 'verify before we buy,'" said Joseph Schumer, branch head for NRL's pulsed power physics group and program manager. "We have learned a lot about the reliability of commercial sources."

Ultraviolet (UV) is light with wavelengths between 200 and 400 nanometers (nm). UV can be divided into 3 bands in this range: UVA (315-400 nm), UVB (280-315 nm), and UVC (200-280 nm). Each band represents a specific part of the UV spectrum and travels through the atmosphere differently. UVC from the Sun is unable to get to the Earth's surface, as the atmosphere will block it.

Testing began in mid-April after NRL received 15 18-watt, hand-held wands from NAVSEA. Since then, the team has tested nine different mercury and xenon-based UV sources with plans to evaluate both LED and plasma-based excimer sources.

"LED and plasma-based sources are emerging technologies, and represent the use of wavelengths not traditionally used for germicidal disinfection," said Huhman. "Mercury sources have historically dominated the market."

Navy researchers continue to evaluate commercial units already being used in hospitals and for other applications for efficacy on Navy-relevant surfaces. The NRL UV team is receiving items on a bi-weekly basis to evaluate.

NRL's work will help identify situations where use of UV provides sufficient viral disinfection at a particular energy level and also develop standard operating procedures to ensure safe UV operation for the Fleet.

Credit: 
Naval Research Laboratory

Grafting with epigenetically-modified rootstock yields surprise

image: The grafted tomato plants involved in the research produced seed that resulted in progeny that were, on average, 35% more productive. And that growth vigor persisted in the progeny over five generations in the study.

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Penn State

UNIVERSITY PARK, Pa. -- Novel grafted plants -- consisting of rootstock epigenetically modified to "believe" it has been under stress -- joined to an unmodified scion, or above-ground shoot, give rise to progeny that are more vigorous, productive and resilient than the parental plants.

That is the surprising finding of a team of researchers that conducted large-scale field trials with tomato plants at three widely separated locations over multiple plant generations. They contend that the discovery, which came from a collaboration between Penn State, the University of Florida and a small start-up company in Nebraska, has major implications for plant breeding.

Because the technique involves epigenetics -- manipulating the expression of existing genes and not the introduction of new genetic material from another plant -- crops bred using this technology could sidestep controversy associated with genetically modified organisms and food. That is the hope of research team leader Sally Mackenzie, professor of plant science in the College of Agricultural Sciences and professor of biology in the Eberly College of Science at Penn State.

"Although we did this with tomato, it can be done with any plant," she said. "We think that this study represents a major breakthrough in showing the potential of epigenetic breeding for crops. And later, it will have major implications for trees and forests in the face of climate change."

Building on previous research conducted by Mackenzie's research group at Penn State, the rootstock came from tomato plants in which researchers manipulated the expression of a gene called MSH1 to induce the "stress memory." That memory is inherited by some progeny, giving them the potential for more vigorous, hardy and productive growth.

The MSH1 gene gave researchers access to the pathway controlling a broad array of plant resiliency networks, explained Mackenzie, who is the Lloyd and Dottie Huck Chair for Functional Genomics and director of the Plant Institute at Penn State. "When a plant experiences a stress such as drought or prolonged extreme heat, it has the ability to adjust quickly to its environment to become phenotypically 'plastic' -- or flexible," she said. "And, it turns out, it 'remembers.'"

The finding that those "remembered" traits passed from the roots through the graft to the top of the plant -- published today (Oct. 22) in Nature Communications -- is hugely important, Mackenzie pointed out. The grafted tomato plants involved in the research produced seed that resulted in progeny that were, on average, 35% more productive -- a stunning outcome, she noted. And that growth vigor persisted in the progeny over five generations in the research.

The plants are hardier, too, according to Mackenzie. During a component of the study at Penn State's Russell E. Larson Agricultural Research Center in 2018, storms dropped more than 7 inches of rain in August, flooding the tomato fields. The pooled water wiped out plants that were part of other research trials. However, the plants that were the offspring of the grafted plants with the epigenetically manipulated rootstock mostly survived -- and then they thrived.

The progeny of the grafted plants also showed superior survivability in the other field trials conducted in California and Florida.

The research is the first true demonstration of an agriculturally amenable epigenetic breeding method, Mackenzie said, adding that the technology is ready to deploy immediately.

"Everything we're doing, any plant breeder in agriculture can do, and now we've shown on a large scale that it has agricultural value. It's ready to go -- a breeder could read about this and implement the system to improve his or her variety," said Mackenzie.

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Penn State

Vanilla cultivation under trees promotes pest regulation

image: Dominik Schwab and field assistant Gatien Rasolofonirina during field research.

Image: 
Annemarie Wurz

The cultivation of vanilla in Madagascar provides a good income for small-holder farmers, but without trees and bushes the plantations can lack biodiversity. Agricultural ecologists from the University of Göttingen, in cooperation with colleagues from the University in Antananarivo (Madagascar), have investigated the interaction between prey and their predators in these cultivated areas. To do this, they experimentally released dummy prey in order to determine the activity of the natural enemies. The result: more prey were attacked as the proportion of trees increased. This pest control is advantageous for agricultural cultivation. The results of the study have been published in the Journal of Applied Ecology.

Vanilla is the most important crop in northwest Madagascar and is sometimes grown together with shade-providing trees in agroforestry systems. The researchers distributed standardised plasticine models of caterpillars in various habitats such as forests, fallow land, vanilla plantations and rice fields. By analysing the bite marks, they were able to analyse the predator attention on these dummy "plant-eaters", i.e. how many predators attacked the prey. The team showed that the predator attention was highest both in the rainforest and in forest fragments, but decreased the fewer trees there were in the area. Even when comparing the landscapes, less dense forest areas had lost a large proportion of their predators. Ants and grasshoppers also played a much greater role as predators than birds or other vertebrates, although the community in the forest differed markedly from the community on cultivated areas. This was also the case in vanilla plantations established directly under the canopies of natural forests.

Dominik Schwab, who produced these results as part of his master's thesis, emphasises: "If rich vegetation with numerous trees is encouraged or restored in the vanilla plantations, it can contribute to nature conservation outside the forests and also promote much better pest control." Co-author and PhD student Annemarie Wurz adds: "Such measures would not reduce the yield, as studies in coffee and cacao agroforestry showed." Professor Teja Tscharntke, head of Agroecology at the University of Göttingen and co-author of the study, says: "The study does not only focus on diversity, but also on an important ecological function of the species involved. In doing so, it supports the United Nations' line, which calls for a decade of ecosystem restoration from 2021 to 2030."

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University of Göttingen

Serum creatinine-to- cystatin C ratio predicts mortality

In patients initiating continuous renal replacement therapy for acute kidney injury, higher serum creatinine-to-cystatin C ratios were associated with lower mortality.

Identifying risk factors for mortality in patients with acute kidney injury (AKI) receiving intensive care and continuous renal replacement therapy (CRRT) is useful for improving assessment of prognosis. In this study of 1,588 patients who underwent CRRT in a single tertiary center intensive care unit, the 30- and 90-day mortality risks were significantly lower in patients with higher creatinine:cystatin C ratio at the time CRRT was begun. This association remained after adjustment for confounding factors. These findings suggest that creatinine:cystatin C ratio may be a simple, useful tool for mortality risk assessment in critically ill patients who develop AKI.

Credit: 
National Kidney Foundation

Transcription factors may inadvertently lock in DNA mistakes

image: An overlay of six X-ray crystal structures of DNA shows that regular (Watson-Crick) and mismatched DNA are similarly bent by the transcription factor TBP. However, the mismatched DNA is highly preferred by the protein because it is easier to distort.

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Maria Schumacher, Duke University

DURHAM, N.C. -- Transcription factor proteins are the light switches of the human genome. By binding to DNA, they help turn genes "on" or "off" and start the important process of copying DNA into an RNA template that acts as a blueprint for a new protein.

By being choosy about which genes they turn on, transcription factors determine which rooms in the house are lighted and which aren't, or rather, which components of a person's genome are activated.

A team of Duke researchers has found that transcription factors have a tendency to bind strongly to "mismatched" sections of DNA, sections of the code that were not copied correctly. The strong binding of transcription factors to mismatched sections of regulatory DNA might be a way in which random mutations become a problem that leads to disease, including cancer.

The findings appear Oct. 21 in the journal Nature.

Most of the time, DNA replication in the body goes smoothly, with nucleotides locking arms with their complementary base pair and marching through the cycle together in intended A-T and C-G fashion. However, as Gordan describes it, "no polymerase is perfect" and every now and then, a nucleotide will be paired with the wrong partner, resulting in a mismatch.

Pipetting transcription factor proteins on slides pre-blotted with thousands of DNA molecule samples, a research team led by Duke computational biologist Raluca Gordan Ph.D., showed that the proteins had a stronger bond with the sections of DNA with the mismatched base pairs than with those with perfectly matched base pairs, or "normal" DNA structure.

But what makes these 'mistakes' an attractive binding site for transcription factor proteins? For insight, Gordan, an associate professor in the Department of Biostatistics and Bioinformatics and the Department of Computer Science, reached out to Hashim Al-Hashimi, Ph.D., a James B. Duke Professor of Biochemistry, and expert in DNA structure and dynamics who works just across the street.

Al-Hashimi studies nucleic acids (DNA and RNA) and their interactions with proteins and small molecules, with the idea that how these biomolecules look and move is as important for their function as their chemical properties.

Looking at the experimental results, Gordan and Al-Hashimi came to the conclusion that the strong interaction between transcription factor proteins and mismatched DNA has a lot to do with laziness. When a transcription factor protein binds to DNA, it must spend energy distorting the site, for example by bending the DNA to its will. However, mismatched sections of DNA are already distorted, so the transcription factor protein has to do less work.

"That's when the transcription factor doesn't need to pay that energetic penalty" to get the job done, Gordan said.

"If we are ever to attain a deep and predictive understanding of how DNA is recognized by proteins in cells, we need to go beyond the conventional description in terms of static structures and move towards describing both DNA and the protein molecules that bind to them in terms of dynamic structures that have different preferences to adopt a wide range of shapes," Al-Hashimi said.

Gordan said that going forward, the team hopes to understand how this interaction relates to disease development. If a mismatched base pair, bound strongly by a transcription factor, makes it through the DNA replication cycle without being repaired by another type of protein--known as a repair enzyme--it can become a mutation, and mutations can lead to genetic diseases like cancer and neurodegeneration.

"We are now convinced that the interactions between transcription factors and mismatches are really strong," she said. "So the next step is to understand what this means for the cell."

"We already know that regulatory regions of the genome harbor more cancer mutations than expected by chance. We just do not know why. The strong interactions between transcription factors and DNA mismatches, which could interfere with repair of the mismatches, provide a novel mechanism for the accumulation of mutations in regulatory DNA."

Credit: 
Duke University

Animal-based research: New experimental design for an improved reproducibility

image: The behavioural biologists tested their newly developed experimental design on mice.

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WWU - Department of Behavioural Biology

In research, the results of studies must be precise and reproducible. For this reason, researchers carried out experiments under strictly standardized laboratory conditions. However, despite the high standards applied, results from individual studies cannot always be reproduced in practice. Especially in cases in which animals are used for research purposes and the original study cannot be repeated, this raises severe ethical questions. For a long time now, researchers have been debating this aspect under the heading "reproducibility crisis". Behavioural scientists at the University of Münster have now been able to demonstrate that a new experimental design can improve the reproducibility and validity of results from studies involving animal experiments. The study has been published in the journal Scientific Reports.

Methodology

What animal scientists usually understand by "standardized experimental conditions" is that for example all the animals are tested on the same day in spring, at the same time and by the same person. Just taking a different season or time, however, can lead to different findings. Nowadays, there are debates more and more often as to whether the very strict standardization might not actually be the cause of numerous non-reproducible results. This is where the empirical study carried out by the Münster researchers comes in.

Instead of testing all the animals used in an experiment under strictly standardized conditions and at one point in time, the researchers split up the one big experiment into smaller, individual ones - so-called 'mini-experiments'. As a result, there were slight differences between 'mini-experiments' in laboratory-specific ambient conditions such as noise level or temperature. "It's important that the biological variation found in real life is reflected in the lab," explains Vanessa von Kortzfleisch, a PhD student with Prof. Helene Richter at the Institute of Neuro- and Behavioural Biology at Münster University and first author of the study. "We were able to demonstrate," she adds, "that changing the design of the experiment slightly has enormous consequences for the knowledge gained."

The new experimental design was tried out on mice from different breeding lines, with several weeks between each 'mini-experiment'. In order to evaluate the reproducibility of the results in both experimental designs, the researchers repeated the same behavioural experiment four times in each design. "The results from the mini-experiment design turned out to be better reproducible than the results from the conventionally used standardized design," says Vanessa von Kortzfleisch.

Improving study designs is one important step towards better reproducible experiments in animal-based research. Although many animal experiments are still indispensable, there is agreement on limiting them to the minimum necessary, with guidance being provided by the "3R concept": replacement, reduction and refinement. The newly developed experimental design is not only easy to implement in research work, it also makes a significant contribution to the refinement and reduction of such experiments.

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University of Münster

GSA publishes three research articles on COVID-19 and aging

The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19. The following were published between October 8 and 21; all are free to access:

National Profiles of Coronavirus Disease – 2019 Mortality Risks by Age Structure and Preexisting Health Conditions: Research article in The Gerontologist by Ashton M. Verdery, PhD, Lauren Newmyer, MA, Brandon Wagner, PhD, and Rachel Margolis, PhD
Acute, Post-Acute, and Primary Care Utilization in a Home-Based Primary Care Program during COVID-19: Research article in The Gerontologist by Karen A. Abrashkin, MD, Jenny Zhang, MD, and Asantewaa Poku, MPH
Helping Amid the Pandemic: Daily Affective and Social Implications of COVID-19-Related Prosocial Activities: Research article in The Gerontologist by Nancy L. Sin, PhD, Patrick Klaiber, MSc, Jin H. Wen, MA, and Anita DeLongis, PhD

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The Gerontological Society of America

Steroid inhalers/pills for asthma linked to heightened risk of brittle bones and fractures

Taking steroid inhalers or tablets to treat asthma or control flare-ups is linked to a heightened risk of brittle bones (osteoporosis) and increased vulnerability to broken bones (fragility fractures), finds research published online in the journal Thorax.

The higher the cumulative dose, and the longer the period of treatment, the greater these risks seem to be, indicate the findings.

Asthma is common, affecting around 334 million people worldwide. And steroid inhalers and tablets are widely used to dampen down airway inflammation and prevent and/or relieve asthma symptoms.

International guidelines recommend a stepwise approach to treating the condition, with steroid inhalers prescribed for the control of moderate to severe disease, and steroid tablets for flare-ups of severe asthma.

Research looking at the impact of steroids on bone health has so far proved inconclusive. The researchers wanted to see if looking separately at dose, number of courses, and steroid type might help to shed further light on the issue.

This is especially important, because international guidance has shifted towards greater use of inhaled steroids for moderately severe asthma while the use of steroid tablets has also increased, say the researchers.

They drew on anonymised health records entered into the nationally representative Clinical Practice Research Datalink (CPRD) GOLD database. This covers more than 15.4 million patients from 738 doctors' surgeries across the UK--equivalent to 7% of the UK population. And they drew on linked Hospital Episode Statistics (HES) data for July 2018, which record all hospital admissions in England.

They used these data to identify all adults with asthma diagnosed between April 2004 and December 2017, and who also had either osteoporosis or fragility fractures. These patients were matched with at least four patients of the same age and gender from the same general practice, but who didn't have osteoporosis or fragility fractures.

The researchers also checked for patients given at least one dose of bisphosphonates--a type of drug used to curb the loss of bone density and stave off osteoporosis--and bone strengthening vitamin D and calcium supplements.

The records were searched for other factors likely to affect bone density, including smoking, weight, and alcohol intake.

The number of prescriptions filled was used to work out the amount and duration of steroid treatment for the 12 months leading up to a diagnosis of osteoporosis or fragility fracture.

Analysis of all the data showed a clear association between both cumulative dose and number of courses of inhaled or steroid tablets and the risk of osteoporosis or fragility fractures.

Two to three steroid tablet prescriptions in the preceding 12 months were linked with larger odds of osteoporosis: those given 9 or more prescriptions and cumulative doses of 2500 mg or more had more than 4 times the risk of those who weren't prescribed these drugs, after accounting for potentially influential factors. They were also more than twice as likely to sustain a fragility fracture.

Similarly, those given 11 or more prescriptions for inhaled steroids were 60% more likely to have osteoporosis and 31% more likely to have fragility fractures than those not prescribed these drugs.

Patients given cumulative doses of more than 120 mg in the preceding year were 20% more likely to sustain a fragility fracture.

Only around half of patients prescribed steroid tablets and even fewer prescribed steroid inhalers were prescribed bisphosphonates in the year leading up to a diagnosis of osteoporosis or fragility fracture, a finding the researchers describe as "disappointing."

But they point out: "Current guidelines on asthma do not fully cover the management of bone comorbidities and no specific bone protection guidance is given. Our results suggest that risk and prevention of osteoporosis and [fragility fractures] should be addressed explicitly in future guideline updates."

This is an observational study, and as such, can't establish cause. And the researchers acknowledge that Inhalers can be difficult to use correctly, so possibly underestimating the actual dose taken. Their analysis also relied on prescriptions and not on actual compliance.

Nevertheless, they conclude: "Both [oral] and [inhaled] steroids are associated with an increased risk of osteoporosis and [fragility fracture] in people with asthma. The use of [these drugs] should be kept to the minimum necessary to treat symptoms and should be stepped down if symptoms and exacerbations are well managed."

And they add that doctors should consider additional bisphosphonate treatment to protect patients' bone health.

Credit: 
BMJ Group

Newly discovered gene may give 'sea pickles' their glow

video: A compilation of manually stimulated Pyrosoma atlanticum bioluminescence taken soon after collection in Brazil.

Image: 
OceanX

A new study describes a bioluminescent gene that could be the reason that so-called "sea pickles," or pyrosomes, an underwater free-floating colony of thousands of tiny animals, reverberate in blue-green light. If confirmed, the finding would be the first bioluminescent gene identified from a chordate--the group that includes all vertebrates as well as a couple types of invertebrates: sea squirts (including pyrosomes) and lancelets. The research is published today in the journal Scientific Reports.

"We know that throughout the tree of life, there are many hundreds of organisms that can produce light and that they do it for a variety of reasons," said co-author Michael Tessler, an assistant professor at St. Francis College who conducted the research while he was a postdoctoral researcher at the American Museum of Natural History. "Our work suggests that there is a common gene shared among at least some animals that, with a few small changes, could be responsible for this bioluminescence. A baseline gene like this could help explain how many of these very different organisms, like a brittle star and the sea pickle, ended up with the same ability to glow."

The idea for this study arose in 2017 when co-author David Gruber, a Museum research associate and a Presidential Professor at Baruch College, was off the coast of Brazil testing a new collecting tool outfitted to a submersible: squishy robotic hands meant to gently grab delicate sea creatures. The expedition team, which included Museum Curator John Sparks and was funded by the Dalio Family Foundation and OceanX, collected a selection of sausage-sized pyrosomes (Pyrosoma atlanticum).

These gelatinous colonies are made of hundreds of tiny animals called zooids--each with a heart and a brain--that work together to move, eat, and breathe. The name pyrosome, which in Greek translates as "fire-body," is derived from their unique bioluminescent displays, which, unlike many bioluminescent animals, can be triggered by light. While pyrosomes attracted the attention of naturalists in the 17th and 18th centuries, many of the most basic facts about their bioluminescence remain elusive.

"Understanding the biochemical pathway for pyrosome bioluminescence is of particular interest because as a chordate, these animals are much more closely related to vertebrates--and to us as humans--than many of the more traditional bioluminescent creatures that might come to mind, things like jellyfish or fireflies," Gruber said.

Like other bioluminescent organisms, pyrosomes rely on a chemical reaction between a substrate (luciferin) and a gene (luciferase) to produce light. The researchers found that mixing a common type of luciferin, called coelenterazine, with Pyrosoma atlanticum resulted in bioluminescence. To further investigate the inner workings of this reaction, they sequenced the RNA of the pyrosomes collected in Brazil as well as from additional specimens found in a large bloom off of Vancouver Island in Canada.

The researchers discovered a gene that matches a luciferase often used in biotechnology that is found in sea pansies, a relative of jellyfish, anemones, and corals. They confirmed that the newly discovered pyrosome gene does, indeed, produce light by expressing it in a bacterial colony and adding coelenterazine.

"Being a part of this study felt like being a part of a century-old mystery novel as to how the pyrosome glows in the dark," said Jean Gaffney, a co-author and assistant professor at Baruch College. "I have never worked with a species that was seemingly so alien, but as a chordate is strikingly similar to us."

A similar gene was recently predicted from a bioluminescent brittle star, indicating that these types of luciferases may have evolved convergently from a baseline gene.

"This study advances the debate about pyrosome bioluminescence," Tessler said. "We provide justification for the idea that this animal produces its own light and it might be able to do so because of a pattern of evolution that as repeated throughout the animal tree of life."

Credit: 
American Museum of Natural History

The biological 'record' of extremely preterm birth differs in men and women

Researchers at McMaster University have found distinct effects of adversity early in life in the genomes of men compared to women who were born extremely preterm.

The study, published online in the journal Development and Psychopathology, followed infants who weighed between 580 and 1000 grams at birth. The cohort was initiated by Saroj Saigal in the Department of Pediatrics in the late 1970's and has been prospectively followed over four decades.

Birth size is a rough indicator of the quality of the perinatal environment, explain researchers. The fetus adapts to cope with the adverse conditions leading to small birth size, which in turn may result in long-lasting changes in the epigenome. The epigenome is the dimension of genomic control that influences gene expression and, ultimately, physiology.

The scientists studied what are known as epigenetic adaptations to early environmental stress.

Being born small and extremely preterm exposes infants to early loss of the protective environment of the womb, postnatal separation from the mother, and life-saving but invasive medical procedures in the hospital. Infant boys are especially vulnerable to these stresses, and respond differently to them than infant girls.

"Premature birth is profoundly traumatic for infants," says Karen Mathewson, a research associate and lead author of the study, who conducted the work with Louis Schmidt, a professor in the Department of Psychology, Neuroscience & Behaviour at McMaster, and Patrick McGowan, an associate professor in the Department of Biological Sciences at the University of Toronto.

"They are simply not ready to lose the safety and protection of the womb or to be separated from the mother. Later in life, problems affecting cognition, emotion, and physical health may develop for some of them," Mathewson says.

For the study, researchers analyzed DNA samples from cheek swabs taken from 45 adults born at extremely low birth weight (ELBW) in the early days of neonatal intensive care, and a comparison group of adults born at normal birth weight, when both groups were in their early thirties.

Mathewson and her team examined DNA methylation (DNAm) levels at 850,000 sites across the genome of each adult in the study. They found multiple sex differences in DNAm in both groups (outside the sex chromosomes), but the number was hugely exaggerated in the ELBW group at nearly 78,000 sites, versus 3,400 sites in the normal birth weight adults. There were also more than 1,350 differences between ELBW men and control men, but women showed almost no differences.

Extreme perinatal adversity appeared to elicite wide-ranging epigenetic changes in men that remained detectable years later. Not only did males born extremely preterm differ greatly from females, they differed significantly from other males.

"The changes in the DNAm profile are a biological record of the past that stretches back to development in the womb. Yet they were still evident in men decades after their exposure to extreme adversity so early in life," says Mathewson.

The DNAm differences between ELBW men and control men were located on genes related to cellular and metabolic processes, neuron development, and interneuron communication, suggesting the possibility of altered long-term physical and mental health in males born extremely preterm.

Precisely how altered DNAm patterns may influence future health is an important follow-up question. The research team recently received additional funding to study how DNAm patterns change over time in adults born at ELBW, and whether they are linked to long-term health or age-related decline.

Credit: 
McMaster University

New evidence for geologically recent earthquakes near Portland, Oregon metro area

image: Trenching begins on the Gales Creek Fault in Oregon.

Image: 
Alison Horst

A paleoseismic trench dug across the Gales Creek fault, located about 35 kilometers (roughly 22 miles) west of Portland, Oregon, documents evidence for three surface-rupturing earthquakes that took place about 8,800, 4,200 and 1,000 years ago.

The findings, published in the Bulletin of the Seismological Society of America, suggest that earthquakes occur about every 4,000 years on the fault. If the full 73-kilometer (45 miles) fault were to rupture, the result could be a magnitude 7.1 to 7.4 earthquake that would pose significant seismic hazard to the Portland metro area, according to Alison Horst and her colleagues.

By comparison, the 1993 Scotts Mills earthquake about 50 kilometers (31 miles) south of Portland was a magnitude 5.7 earthquake, and caused damages totaling about $30 million, the researchers noted.

The region is part of the seismically active Cascadia subduction zone, where the Juan de Fuca tectonic plate bends beneath the North American plate. The Gales Creek fault lays within the Cascadia forearc, the land wedged between the oceanic trench where the Juan de Fuca begins its bend and the line of Cascadia volcanoes in Washington State and Oregon that are fueled by the subducting plate.

"In general, little paleoseismic work has been done on forearc faults in Oregon, but many faults in the region are of interest based on their proximity to population centers," said Horst, a paleoseismologist formerly at Portland State University and now at the Washington State Department of Resources.

Mapping and analyzing faults in the Pacific Northwest can be difficult, since fault surface traces are often covered by urban development and thick forests, or are difficult to reach in mountainous areas. To learn more about possible recent seismic activity along these forearc faults, Horst and her colleagues dug a trench across the Gales Creek fault, which had been mapped previously and is being investigated by the U.S. Bureau of Reclamation and the U.S. Geological Survey along part of the fault that projected through Scoggins Dam in Oregon's Washington County

The Reclamation project had turned up evidence of surface deformation along the fault in sediments from the most recent geological time period, called the Holocene. After digging a trench across the fault--first by hand and later by backhoe--the researchers looked for evidence of past earthquakes in the rock layers, assigning an estimated date for each earthquake using radiocarbon analysis of charcoal contained in the layers.

The trenching turned up strong evidence for at least three Holocene-age surface-rupturing earthquakes along the fault, with some weaker signs of one potential earthquake occurring after 1,000 years ago, and one earthquake occurring before 8,800 years ago.

The researchers also estimated the magnitude of an earthquake that would rupture the entire mapped length of the Gales Creek fault, assuming that the full length ruptured at once and that the rupture event did not extend across multiple faults.

"The linkage between rupture on the Gales Creek fault and neighboring faults is still unknown, as there are no other paleoseismic studies with earthquake ages for neighboring faults and as a result no indication of paleo-earthquakes with overlapping age estimates on neighboring faults," Horst explained. "Future work on faults in the region could allow us to improve our understanding of the connectivity of rupture on these low slip, long recurrence forearc faults."

The findings suggest that other faults within the Oregon portion of the Cascadia forearc should be studied for signs of Holocene earthquakes, the researchers concluded.

Credit: 
Seismological Society of America

An ultrasonic projector for medicine

image: Stuttgart researchers are writing the alphabet using micro-particles by modulating sound pressure profiles. Depending on the sound pressure, the particles collect and form letters. With the letter images, the team demonstrates the possibilities of the ultrasound modulator, which will likely be used primarily in medicine.

Image: 
MPI for Intelligent Systems

A chip-based technology that generates sound profiles with high resolution and intensity could create new options for ultrasound therapy, which would become more effective and easier. A team of researchers led by Peer Fischer from the Max Planck Institute for Intelligent Systems and the University of Stuttgart has developed a projector that flexibly modulates three-dimensional ultrasound fields with comparatively little technical effort. Dynamic sound pressure profiles can thus be generated with higher resolution and sound pressure than the current technology allows. It should soon be easier to tailor ultrasound profiles to individual patients. New medical applications for ultrasound may even emerge.

Ultrasound is widely used as a diagnostic tool in both medicine and materials science. It can also be used therapeutically. In the US, for example, tumours of the uterus and prostate are treated with high-power ultrasound. The ultrasound destroys the cancer cells by specific heating of the diseased tissue. Researchers worldwide are using ultrasound to combat tumours and other pathological changes in the brain. "In order to avoid damaging healthy tissue, the sound pressure profile must be precisely shaped", explains Peer Fischer, Research Group Leader at the Max Planck Institute for Intelligent Systems and professor at the University of Stuttgart. Tailoring an intensive ultrasound field to diseased tissue is somewhat more difficult in the brain. This is because the skullcap distorts the sound wave. The Spatial Ultrasound Modulator (SUM) developed by researchers in Fischer's group should help to remedy this situation and make ultrasound treatment more effective and easier in other cases. It allows the three-dimensional shape of even very intense ultrasound waves to be varied with high resolution - and with less technical effort than is currently required to modulate ultrasound profiles.

High intensity sound pressure profiles with 10,000 pixels

Conventional methods vary sound fields with several individual sound sources, the waves of which can be superimposed and shifted against each other. However, because the individual sound sources cannot be miniaturized at will, the resolution of these sound pressure profiles is limited to 1000 pixels. The sound transmitters are then so small that the sound pressure is sufficient for diagnostic but not therapeutic purposes. With the new technology, the researchers first generate an ultrasonic wave and then modulate its sound pressure profile independently, essentially killing two birds with one stone. "In this way, we can use much more powerful ultrasonic transducers", explains postdoctoral fellow Kai Melde, who is part of the team that developed the SUM. "Thanks to a chip with 10,000 pixels that modulates the ultrasonic wave, we can generate a much finer-resolved profile".

"In order to modulate the sound pressure profile, we take advantage of the different acoustic properties of water and air", says Zhichao Ma, a post-doctoral fellow in Fischer's group, who was instrumental in developing the new SUM technology: "While an ultrasonic wave passes through a liquid unhindered, it is completely reflected by air bubbles". The research team from Stuttgart thus constructed a chip the size of a thumbnail on which they can produce hydrogen bubbles by electrolysis (i.e. the splitting of water into oxygen and hydrogen with electricity) on 10,000 electrodes in a thin water film. The electrodes each have an edge length of less than a tenth of a millimetre and can be controlled individually.

A picture show with ultrasound

If you send an ultrasonic wave through the chip with a transducer (a kind of miniature loudspeaker), it passes through the chip unhindered. But as soon as the sound wave hits the water with the hydrogen bubbles, it continues to travel only through the liquid. Like a mask, this creates a sound pressure profile with cut-outs at the points where the air bubbles are located. To form a different sound profile, the researchers first wipe the hydrogen bubbles away from the chip and then generate gas bubbles in a new pattern.

The researchers demonstrated how precisely and variably the new projector for ultrasound works by writing the alphabet in a kind of picture show of sound pressure profiles. To make the letters visible, they caught micro-particles in the various sound pressure profiles. Depending on the sound pattern, the particles arranged themselves into the individual letters.

Organoid models for drug testing

For similar images, the scientists collaborating with Peer Fischer, Kai Melde, and Zhichao Ma previously arranged micro-particles with sound pressure profiles, which they modelled using a slightly different technique. They used special plastic stencils to deform the pressure profile of an ultrasonic wave like a hologram and arrange small particles - as well as biological cells in a liquid - into a desired pattern. However, the plastic holograms only provided still images. For each new pattern, they had to make a different plastic template. Using the ultrasound projector, the Stuttgart team is able to generate a new sound profile in about 10 seconds. "With other chips, we could significantly increase the frame rate", says Kai Melde, who led the hologram development team.

The technique could be used not only for diagnostic and therapeutic purposes but also in biomedical laboratories. For example, to arrange cells into organoid models. "Such organoids enable useful tests of active pharmaceutical ingredients and could therefore at least partially replace animal experiments", says Fischer.

Credit: 
Max-Planck-Gesellschaft

A trillion turns of light nets terahertz polarized bytes

image: Alessandro Alabastri is an assistant professor of electrical and computer engineering in Rice University's George R. Brown School of Engineering.

Image: 
Photo by Jeff Fitlow/Rice University

HOUSTON - (Oct. 19, 2020) - U.S. and Italian engineers have demonstrated the first nanophotonic platform capable of manipulating polarized light 1 trillion times per second.

"Polarized light can be used to encode bits of information, and we've shown it's possible to modulate such light at terahertz frequencies," said Rice University's Alessandro Alabastri, co-corresponding author of a study published this week in Nature Photonics.

"This could potentially be used in wireless communications," said Alabastri, an assistant professor of electrical and computer engineering in Rice's Brown School of Engineering. "The higher the operating frequency of a signal, the faster it can transmit data. One terahertz equals 1,000 gigahertz, which is about 25 times higher than the operating frequencies of commercially available optical polarization switches."

The research was a collaboration between experimental and theoretical teams at Rice, the Polytechnic University of Milan (Politecnico) and the Italian Institute of Technology (IIT) in Genoa. This collaboration started in the summer of 2017, when study co-first author Andrea Schirato was a visiting scholar in the Rice lab of physicist and co-author Peter Nordlander. Schirato is a Politecnico-IIT joint graduate student under the supervision of co-corresponding author Giuseppe Della Valle of Politecnico and co-author Remo Proietti Zaccaria of IIT.

Each of the researchers work in nanophotonics, a fast-growing field that uses ultrasmall, engineered structures to manipulate light. Their idea for ultrafast polarization control was to capitalize on tiny, fleeting variations in the generation of high-energy electrons in a plasmonic metasurface.

Metasurfaces are ultrathin films or sheets that contain embedded nanoparticles that interact with light as it passes through the film. By varying the size, shape and makeup of the embedded nanoparticles and by arranging them in precise two-dimensional geometric patterns, engineers can craft metasurfaces that split or redirect specific wavelengths of light with precision.

"One thing that differentiates this from other approaches is our reliance on an intrinsically ultrafast broadband mechanism that's taking place in the plasmonic nanoparticles," Alabastri said.

The Rice-Politecnico-IIT team designed a metasurface that contained rows of cross-shaped gold nanoparticles. Each plasmonic cross was about 100 nanometers wide and resonated with a specific frequency of light that gave rise to an enhanced localized electromagnetic field. Thanks to this plasmonic effect, the team's metasurface was a platform for generating high-energy electrons.

"When one laser light pulse hits a plasmonic nanoparticle, it excites the free electrons within it, raising some to high-energy levels that are out of equilibrium," Schirato said. "That means the electrons are 'uncomfortable' and eager to return to a more relaxed state. They return to an equilibrium in a very short time, less than one picosecond."

Despite the symmetric arrangement of crosses in the metasurface, the nonequilibrium state has asymmetric properties that disappear when the system returns to equilibrium. To exploit this ultrafast phenomenon for polarization control, the researchers used a two-laser setup. Experiments performed by study co-first author Margherita Maiuri at Politecnico's ultrafast spectroscopy laboratories -- and confirmed by the team's theoretical predictions -- used an ultrashort pulse of light from one laser to excite the crosses, allowing them to modulate the polarization of light in a second pulse that arrived less than a picosecond after the first.

"The key point is that we could achieve the control of light with light itself, exploiting ultrafast electronic mechanisms peculiar of plasmonic metasurfaces," Alabastri said. "By properly designing our nanostructures, we have demonstrated a novel approach that will potentially allow us to optically transmit broadband information encoded in the polarization of light with unprecedented speed."

Credit: 
Rice University

Newborn brains lack maturity to process emotions as adults do

COLUMBUS, Ohio - Humans aren't born with mature brain circuitry that attaches emotions to the things they see or hear in their environment, a new study shows.

Researchers studying brain scans of newborns found that the part of the brain involved in experiencing emotions isn't functionally connected in a mature way with the regions that process visual or auditory stimuli.

In adults, the connections between those parts of the brain allow us to feel fear when we see a bear in the woods or love when we see the face of a family member.

But it appears that it takes at least a few months for babies to be able to connect what they see with specific higher-level emotions, said Zeynep Saygin, co-author of the study and assistant professor of psychology at The Ohio State University.

"It's a finding we didn't really expect. We thought these connections might be mature right from birth," said Saygin, who is a core faculty member of Ohio State's Chronic Brain Injury Program.

"This suggest that newborns analyze the emotional content of their surroundings at only a very basic level."

Saygin conducted the study with Heather Hansen and Jin Li, graduate students in psychology at Ohio State. Their results were published today in the journal PLOS ONE.

The researchers analyzed fMRI scans of the brains of 40 newborns, all less than a week old, who were part of the Developing Human Connectome Project. They compared these to similar scans from 40 adults who participated in the separate Human Connectome Project.

They were looking for the connections between the amygdala, the part of the brain involved with experiencing emotions, and the occipitotemporal (or visual) cortex, which is primarily involved with processing stimuli from what we see.

"The amygdala tags visual stimuli with an emotional value," Saygin said.

"For example, is this thing I am seeing dangerous? Should I be afraid? Should I approach it or avoid it?"

In adults, there is a specific form of functional connection between the two parts of the brain, Saygin said. The amygdala has a stronger connection to high-level sensory regions of the visual cortex - the part that processes faces, bodies and objects. These are the types of stimuli that may warrant an emotional reaction.

The amygdala in adults is not as strongly connected to the primary sensory regions of the visual cortex, which are involved with detecting angles, lines, edges and light, things that have less emotional content.

Moreover, adults show a similar pattern for auditory regions too. In adults, the amygdala has a stronger connection to high-level auditory regions, like regions that process speech, and a weaker connection to primary auditory regions, such as regions that detect frequency information.

"Seeing this pattern for both visual and auditory regions was affirming, as it demonstrates that the amygdala connects more with areas that process complex stimuli - things that would warrant an emotional response - and not just to areas that are closer in proximity to the amygdala," said Hansen, lead author of the study.

This study found that newborns, unlike adults, had similar types of connections between the amygdala and all parts of the visual and auditory cortex, with not much differentiation among them.

Other research suggests that the more adult-like connections are present in babies within a few months after birth. But this is the first study to look at newborns, Saygin said.

"We believe that babies need more visual experience and maturation in order to be able to attach emotional value to visual stimuli," she said.

Saygin's lab at Ohio State is currently studying babies from birth to age 3 to learn more about how and when young children develop the ability to connect what they see with the proper emotion.

The research has important clinical implications because the amygdala has a role in a variety of disorders that begin early in life, including autism and anxiety.

"It is crucial to fully understand how the amygdala connects to the rest of the brain across early development," she said.

"By learning about the course of its development, we should be able to say what is typical and how it may go awry. That may lead us to new diagnostic and treatment interventions."

Credit: 
Ohio State University

Glimpse deep into Earth's crust finds heat source that may stabilize continents

image: Rocks collected from Kilbourne Hole crater in New Mexico revealed the thinning lithosphere in the Rio Grande continental rift provides heat necessary to stabilize continents over billions of years.

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Penn State

Rocks from the Rio Grande continental rift have provided a rare snapshot of active geology deep inside Earth's crust, revealing new evidence for how continents remain stable over billions of years, according to a team of scientists.

"We tend to study rocks that are millions to billions of years old, but in this case we can show what's happening in the deep crust, nearly 19 miles below the surface of the Earth, in what geologically speaking is the modern day," said Jacob Cipar, a graduate student in geosciences at Penn State. "And we have linked what's preserved in these rocks with tectonic processes happening today that may represent an important step in the development of stable continents."

The team, led by Penn State scientists, found evidence that heat from the mantle is melting the lower crust at the rift, where tectonic forces are pulling apart and thinning the lithosphere, or the crust and upper mantle that make up the rigid outer layer of Earth.

Heating the continental crust is considered important to its development. But the process is often associated with crustal thickening, when continental plates collide and form mountains like the Himalayas, the scientists said.

"Our research suggests that these rocks that have been thought of as related to mountain building may have actually been cooked by a thinning lithosphere like what's happening in the modern-day Rio Grande rift," Cipar said. "And more broadly, thinning lithosphere may be more important than previously recognized for stabilizing continents and preventing them from sinking back into the mantle."

The researchers recently reported their findings in the journal Nature Geoscience.

Earth's continents feature a unique silicon-rich, buoyant crust that allows land to rise above sea level and host terrestrial life, the scientists said. The crust also contains heat-producing elements like uranium that could destabilize it over geological time.

Heating the crust creates molten rock that carries those elements toward the surface, resulting in a cooler and stronger lower crust that can protect continents from being absorbed into the mantle, the scientists said. But questions remain about the sources of that heat.

"We are suggesting that thinning of the lithosphere is really the removal of a barrier that keeps that heat away from the crust," said Andrew Smye, assistant professor of geosciences at Penn State and Cipar's adviser. "Removing or thinning that barrier at the Rio Grande rift appears to be what is generating the heat needed to initiate this process of stabilizing continental crust. And this has been overlooked in our understanding of how continents become so stable."

The scientists tapped into rocks brought to the surface 20,000 years ago by volcanoes in New Mexico. The rocks are considered geologically young and are significant because they retain the context of the lower crust, the scientists said.

"In contrast, what we see in the rock record around the world is that oftentimes what it takes to get them up to the surface has disrupted their original relationship with the lower crust," said Joshua Garber, a postdoctoral researcher at Penn State. "This makes it really challenging to use older rocks to try to understand tectonics, and it makes the Rio Grande probably the best place to do this research."

The scientists used analytical techniques to link the age of minerals in the rocks to the pressure and temperature they faced as they made their way through the crust.

Similarities between the pressure and temperature path from the Rio Grande lower crust and rocks from other locations suggest that a thinning lithosphere is important for stabilizing Earth's continents, the scientists said.

"The snapshots of data we do have from other locations really nicely aligns with what we found in the Rio Grande rift," Garber said. "So that tells us this is not just happening now in the western United States. This shows the guts of continents have probably undergone this globally at least for the last billion years."

Credit: 
Penn State