Brain

CHAPEL HILL, North Carolina--Researchers have discovered a gene, OTUD7A, that impacts the development of Ewing sarcoma, a bone cancer that occurs mainly in children. They have also identified a compound that shows potential to block OTUD7A protein activity. The finding, by scientists at the University of North Carolina and the Lineberger Comprehensive Cancer Center, appeared online June 1, 2021, in Advanced Science.

About 250 children and young adults are diagnosed with Ewing sarcoma each year in the U.S. About half of those diagnosed will ultimately succumb to the disease, pointing to the need for better therapies.

"Our primary research focus targeted the EWS-FLI1 fusion protein found in about 85 percent of Ewing sarcoma patients," said UNC Lineberger's Pengda Liu, PhD, assistant professor of Biochemistry and Biophysics in the UNC School of Medicine and co-lead author. "This protein, made up of pieces of two other proteins, is unique to Ewing sarcoma and only produced in cancer cells, making it an excellent target for treatment."

Critical relationships between proteins contribute to the development of cancers such as Ewing sarcoma. So, it was a seminal discovery when the UNC researchers found that OTUD7A controls the cancer-causing fusion protein.

Armed with this knowledge, the scientists went on the hunt for small molecule compounds that could block OTUD7A's activity. Their collaborator, Atomwise Inc., used an artificial intelligence program known as AtomNet to screen four million small molecules to find ones that could fit into a pocket in OTUD7A. One compound they identified, 7Ai, showed a good ability to reduce tumor formation in mice that were grafted with human Ewing sarcoma cells. The compound did not appear to be toxic and was well-tolerated. Also, 7Ai did not kill normal cells that were tested in lab culture experiments.

"Treatment with 7Ai could provide a new targeted therapeutic option for patients who become resistant to chemotherapy. Developing an effective drug will require more lab work and then clinical studies, however," said Liu.

"By deeply exploring the key cellular processes that lead to cancer, unexpected potential therapeutic avenues can result," said co-author Ian Davis, MD, PhD, G. Denman Hammond Professor of Childhood Cancer and co-leader of the Cancer Genetics Program at UNC Lineberger. "Once the basic science validated our biological approaches, the application of computational virtual screening enabled us to quickly identify a lead molecule for further testing and validation."

The researchers are currently working with the UNC Eshelman School of Pharmacy to improve 7Ai's potency and specificity.

"I am particularly indebted to a UNC student with metastatic Ewing sarcoma who made it a priority to donate tissue that could be used for research," said Davis, who is also the associate division chief of pediatric hematology-oncology. "We're also appreciative of funding for our research through an NIH Beau Biden Pediatric Cancer Moonshot grant, which came about after the cancer-related death of President Biden's son."

The genetic material of most organisms is carried by DNA, a complex organic molecule. DNA is very long -- for humans, the molecule is estimated to be about 2 m in length. In cells, DNA occurs in a densely packed form, with strands of the molecule coiled up in a complicated but efficient space-filling way. A key role in DNA's compactification is played by histones, structural-support proteins around which a part of a DNA molecule can wrap. The DNA-histone wrapping process is reversible -- the two molecules can unwrap and rewrap -- but little is known about the mechanisms at play. Now, by applying high-speed atomic-force microscopy (HS-AFM), Richard Wong and colleagues from Kanazawa University (NanoLSI WPI) provide valuable insights into the spatiotemporal dynamics of DNA-histone interactions.

The researchers looked at the interaction between DNA and a histone called H2A, one of the five main histones. To check the applicability of HS-AFM as a viable tool for imaging the DNA-histone interaction, they first focused on H2A in its native state. Wong and colleagues were able to image the topology of the molecule, and how it changes over time. Importantly, they showed that the HS-AFM process, during which a tapping force is constantly exerted on the molecule, does not lead to conformational changes or actual damage.

For real-time observation of the DNA-H2A interaction with HS-AFM, the scientists prepared DNA samples with different lengths and forms: plasmid (long and circular), long-linearized and short-linearized DNA, with the latter having the highest motility. The experiments showed that the choice of substrate on which to put the DNA for AFM imaging is crucial; a particular type of lipid layer was found to be good as it does not strongly absorb DNA strands.

The observations of the interaction of H2A with short-linearized DNA, which the researchers nicknamed 'inchworm DNA', led to the most notable results. Specifically, four different interaction situations could be distinguished: touching, sliding, sandwiching and wrapping, with the associated motions indeed resembling the movements of inchworms.

Wong and colleagues also investigated the effect of ionic strength on the DNA-histone binding affinity, by changing the salt concentration of the liquid containing the DNA-histone aggregate. When increasing the liquid's salinity, the aggregate was found to dissolve. When diluting the liquid again -- and so reducing the salt content -- the aggregate reformed. This result shows that varying the ionic strength (i.e., the salt concentration) of the environment of the DNA-H2A complex provides a way to mimic the variations in the strength of DNA-histone interactions as they happen in living organisms.

The report of Wong and colleagues represents the first real-time observation of DNA-histone interactions, and convincingly shows the applicability of HS-AFM for studying this kind of biological process, also in the context of diseases. Quoting the researchers: "[Our work] demonstrates ... the potential to study protein aggregation and protein-nucleic acid aggregate formation in various human diseases."

Finally, it is worth highlighting the contribution of the paper's first author, Goro Nishide, who is a pre-doctoral student at the Division of Nano Life Science in the Graduate School of Frontier Science Initiative at Kanazawa University. Mr Nishide played a key role in the reported research, supervised by Professor Wong and Dr. Lim, by performing the experiments, co-designing the study and co-writing the paper. Mr Nishide is also enrolled in Kanazawa University's WISE program for Nano-Precision Medicine, Science and Technology, an initiative aimed at innovations in disease prevention, diagnosis, and treatment methods based on exploiting our increased understanding of biological and other processes at the nanoscale.

[Background]

Atomic force microscopy
Atomic force microscopy (AFM) is an imaging technique in which the image is formed by scanning a surface with a very small tip. Horizontal scanning motion of the tip is controlled by piezoelectric elements, while vertical motion is converted into a height profile, resulting in a height distribution of the sample's surface. As the technique does not involve lenses, its resolution is not restricted by the so-called diffraction limit as in X-ray diffraction, for example. In a high-speed setup (HS-AFM), the method can be used to produce movies of a sample's structural evolution in real time, as a typical biomolecule can be scanned in 100 ms or less. Now, Richard Wong and colleagues from Kanazawa University have successfully applied the HS-AFM technique to study the wrapping of DNA around structural proteins.

Division of Nano Life Science in the GRAFINITI and WISE program at Kanazawa University
Goro Nishide, the first author of the paper reporting the application of HS-AFM for visualizing DNA-histone dynamics, is a pre-doctoral student at the Division of Nano Life Science in the Graduate School of Frontier Science Initiative (GRAFINITI), an educational program at Kanazawa University fostering excellent graduate students wishing to participate in establishing the new scientific field of "Nano Probe Life Science". The students' supervisors for this program are all world-class researchers affiliated to the WPI-Nano Life Science Institute (WPI-NanoLSI), a research center established in 2017 as part of Japan's World Premier International Research Center Initiative (WPI) of the Ministry of Education, Culture, Sports, Science and Technology, the objective of which is the creation of world-tier research centers.
In addition, Mr Nishide is enrolled in Kanazawa University's WISE Program for Nano-Precision Medicine, Science, and Technology. Notably, WISE is a five-year integrated pre- and post-doctoral degree program that focuses on five types of diseases in humans (cancer, lifestyle diseases, neurological diseases, diseases caused by small particulates, and diseases caused by nanomaterials). Its mission is to foster technically skilled medical and engineering professionals who all contribute to the creation of innovative disease prevention, diagnosis, and treatment methods through understanding and control on the nanoscale level. The WISE program is nurtured by a community of scientists from four domains (nanometrology, life sciences, supramolecular chemistry, and computational science), all engaging in transdisciplinary dialogue.

The Water Oxidation Reaction (WOR) is one of the most important reactions on the planet since it is the source of nearly all the atmosphere's oxygen. Understanding its intricacies can hold the key to improve the efficiency of the reaction. Unfortunately, the reaction's mechanisms are complex and the intermediates highly unstable, thus making their isolation and characterisation extremely challenging. To overcome this, scientists are using molecular catalysts as models to understand the fundamental aspects of water oxidation - particularly the oxygen-oxygen bond-forming reaction.

For the first time, scientists in ICIQ's Lloret-Fillol group, who are minutely studying WOR, have isolated and fully characterised an elusive intermediate generated after the oxygen-oxygen bond formation event - the reaction's rate-determining step. The work, an international effort led by ICIQ in collaboration with University of Groningen (The Netherlands) and Synchrotron SOLEIL (France), has been published in Nature Chemistry, "Our work has direct implications in our capacity to look at the oxygen-oxygen bond formation step and the afterwards reaction intermediates," explains Julio Lloret-Fillol, ICIQ group leader and ICREA professor, lead author of the paper.

By modifying the conditions in their catalytic system, the researchers have crystallised the Ru(IV) side-on peroxo generated after the rate determining step of the reaction, the oxygen-oxygen bond formation event. "The paper will help to better understand the mechanism of the oxygen-oxygen bond formation, since it shows direct evidence for a single-site mechanism to form the oxygen-oxygen bond, one of the mechanisms postulated for photosystem II," claims Carla Casadevall, former PhD student of the Lloret group, now a Marie Sk?odowska-Curie postdoctoral researcher at the Erwin Reisner group at the University of Cambridge and first author of the paper.

Despite extensive efforts to elucidate its mechanism, WOR is still not fully understood, prompting an ongoing debate with several proposals concerning the formation mechanism of the oxygen-oxygen bond. The researchers have used labelling studies to monitor the intermediates formed both before and after the rate-determining step of WOR. This way, they have been able to provide direct evidence of the formation of the oxygen-oxygen bond by water nucleophilic attack from the metal-oxo.

"This paper proves again that well-defined molecular complexes offer access to fundamental aspects of WOR, otherwise very challenging, which will be useful for further efficient catalyst design," concludes Casadevall.

Centuries-old smoke particles preserved in the ice reveal a fiery past in the Southern Hemisphere and shed new light on the future impacts of global climate change, according to new research published in Science Advances.

"Up till now, the magnitude of past fire activity, and thus the amount of smoke in the preindustrial atmosphere, has not been well characterized," said Pengfei Liu, a former graduate student and postdoctoral fellow at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and first author of the paper. "These results have importance for understanding the evolution of climate change from the 1750s until today, and for predicting future climate."

One of the biggest uncertainties when it comes to predicting the future impacts of climate change is how fast surface temperatures will rise in response to increases in greenhouse gases. Predicting these temperatures is complicated since it involves the calculation of competing warming and cooling effects in the atmosphere. Greenhouse gases trap heat and warm the planet's surface while aerosol particles in the atmosphere from volcanoes, fires and other combustion cool the planet by blocking sunlight or seeding cloud cover. Understanding how sensitive surface temperature is to each of these effects and how they interact is critical to predicting the future impact of climate change.

Many of today's climate models rely on past levels of greenhouse gasses and aerosols to validate their predictions for the future. But there's a problem: While pre-industrial levels of greenhouse gasses are well documented, the amount of smoke aerosols in the preindustrial atmosphere is not.

To model smoke in the pre-industrial Southern Hemisphere, the research team looked to Antarctica, where the ice trapped smoke particles emitted from fires in Australia, Africa and South America. Ice core scientists and co-authors of the study, Joseph McConnell and Nathan Chellman from the Desert Research Institute in Nevada, measured soot, a key component of smoke, deposited in an array of 14 ice cores from across the continent, many provided by international collaborators.

"Soot deposited in glacier ice directly reflects past atmospheric concentrations so well-dated ice cores provide the most reliable long-term records," said McConnell.

What they found was unexpected.

"While most studies have assumed less fire took place in the preindustrial era, the ice cores suggested a much fierier past, at least in the Southern Hemisphere," said Loretta Mickley, Senior Research Fellow in Chemistry-Climate Interactions at SEAS and senior author of the paper.

To account for these levels of smoke, the researchers ran computer simulations that account for both wildfires and the burning practices of indigenous people.

"The computer simulations of fire show that the atmosphere of the Southern Hemisphere could have been very smoky in the century before the Industrial Revolution. Soot concentrations in the atmosphere were up to four times greater than previous studies suggested. Most of this was caused by widespread and regular burning practiced by indigenous peoples in the pre-colonial period," said Jed Kaplan, Associate Professor at the University of Hong Kong and co-author of the study.

This result agrees with the ice core records that also show that soot was abundant before the start of the industrial era and has remained relatively constant through the 20th century. The modelling suggests that as land use changes decreased fire activity, emissions from industry increased.

What does this finding mean for future surface temperatures?

By underestimating the cooling effect of smoke particles in the pre-industrial world, climate models might have over-estimated the warming effect of carbon dioxide and other greenhouse gasses in order to account for the observed increases in surface temperatures.

"Climate scientists have known that the most recent generation of climate models have been over-estimating surface temperature sensitivity to greenhouse gasses, but we haven't known why or by how much," said Liu. "This research offers a possible explanation."

"Clearly the world is warming but the key question is how fast will it warm as greenhouse gas emissions continue to rise. This research allows us to refine our predictions moving forward," said Mickley.

A study examining Japanese schools' hands-off approach when children fight showed it could create opportunities for autonomy and encourage ownership of solutions, suggesting a new strategy in handling kids squabbles in other countries.

Called mimamoru, the pedagogical strategy is a portmanteau of the Japanese words mi, meaning watch, and mamoru, meaning guard or protect. It is generally understood as "teaching by watching" -- where adults, including early childhood educators, intentionally let kids handle disagreements on their own to promote their learning through voluntary exploration and actions. While not an official part of Japan's early childhood education and care (ECEC) curriculum, it is treated as an implicit guideline. The approach reflects Japanese socialization practices at home and school, where it is a norm for grownups to wait for children to respond to problems and guide them to take ownership of their learning.

"This study aims to understand the reason why Japanese early childhood educators tend not to intervene, and how and in what contexts they do," said study author Fuminori Nakatsubo, ECEC specialist and associate professor at Hiroshima University's Graduate School of Humanities and Social Sciences.

The researchers said insights gleaned from exploring the mimamoru approach could provide educators with fresh perspectives on disciplinary practices, particularly in countries where direct and immediate intervention is prioritized.

Maximizing learning through minimal intervention

A total of 34 Japanese and 12 US early childhood educators participated in focus groups that used modified video-cued multi-vocal ethnography methods to scrutinize the non-intervention strategy. After watching a three-minute clip showing it in action at a private preschool in western Japan, the international mix of educators discussed non-verbal cues exhibited by the students and teachers and the timing of intervention. Their findings are published in the Early Childhood Education Journal.

It may seem counterintuitive to just stand by when youngsters are in a tussle. But the approach sees conflicts as a valuable opportunity for learning which adults can rob kids from gaining if they immediately intercede. Stepping in and judging kids' behaviors may also inadvertently set them up as good and bad, impacting relationships negatively.

The study noted that allowing children to experience a feeling of "It hurts!" (physical pain) or "Oh no, I shouldn't have done it!" (guilt) can be a teachable moment that physical fights do not solve any problem.

Mimamoru's three major characteristics

The researchers, however, clarified that "watching" doesn't mean that adults ignore the safety of children. Japanese educators intervene when the risk of physical harm caused by fighting is greater than the benefit for children to learn.

Japanese and US educators highlighted mimamoru's three major characteristics: temporary, minimal intervention to reduce the immediate risk of physical harm; non-intervention or staying out of the fight to encourage kids to solve their problem; and non-presence or leaving the children by themselves once determined that they can sort out their dilemma without adult support.

Selecting which to apply among these three relies heavily on an educator's patience in balancing benefits vis-a-vis threats, careful observation of behaviors, and trust in the children's capacity to learn from their own experiences.

"Although the mimamoru approach looks passive, it rather challenges educators to remain patient, watching and waiting for children to think and act on their own. An underlying assumption of this Japanese practice is adults' trust in children's inherent goodness, more specifically, their ability to learn through everyday social interactions," the researchers explained.

"In other words, children learn through their exploration of autonomy under the protection of adults."

US participants in the study raised how policies to protect children from any physical harm may not allow educators in their country to wait for kids to solve their own problems. But they recognized that it might be worth trying it out in their classrooms once they secured parental consent and applied some modifications that fit with the country's educational and policy contexts.

Nakatsubo said he hopes their research revealed the "hidden strengths" inherent in the approach of Japanese educators.

The work was conducted under the auspices of the Russian Foundation for Basic Research and organizations-participants of the BRICS framework program in science, technology and innovation; the grant title is "Nanosized peptide-based biomaterials for photodynamic diagnostics of tumors".

Project lead, Chief Research Associate of KFU's Bionanotechnology Lab Rawil Fakhrullin commented on the results, "The development of materials for theranostics (simultaneous early diagnosis and therapy of diseases) is one of the most urgent tasks in modern chemistry and biomedicine. A feature of such materials is the combination of at least two functions: sensory and therapeutic. Various nanoparticles capable of targeted drug delivery into cells and tissues are used as carrier particles in theranostic formulations. The most promising are organic nanoparticles. Peptide nanomaterials are now actively used as drug delivery vehicles. The interest in peptide complexes is stimulated by their biological compatibility and safety, as well as the modification of their properties using various covalently attached ligands."

Using covalent self-assembly, the team managed to synthesize new functional supramolecular systems based on dipeptides and genipin (a cross-sewing agent derived from plant material). The particles are polymer spheres 200-300 nanometers in diameter.

"The obtained peptide complexes are highly stable, have a low level of auto-fluorescence and can be used for in vitro labeling of cells, for example, to detect migration, including the integration of stem cells into the damaged area and distribution in multicellular clusters," said Fakhrullin. "The specifics of this work was the use of hyperspectral microscopy for visualization of nanoparticles in human cells and the body of Turbatrix aceti nematodes. We have established that peptide nanoparticles have the ability to efficiently scatter light and can be identified by characteristic spectral curves in visible light. This property of peptide nanoparticles makes possible their visualization without the use of fluorescent labels in living cells and organisms, without lengthy sample preparation and specific coloring."

He also said that studying the interactions between peptide nanomaterials and cells or organisms is crucial for understanding the biological function and the mechanism of action of peptide materials. This is very important for further clinical practice.

COLUMBUS, Ohio - If you've watched a slasher movie, you've probably been exposed to the final girl trope - a closing scene of a white, suburban teenage girl who triumphed over a threatening monster and lived to tell the tale.

But her story doesn't stop there - in some ways, a whole new life, overshadowed by trauma, has only just begun, Ohio State University graduate student Morgan Podraza posits in an article published in the journal Horror Studies.

Consider actor Jamie Lee Curtis' depiction of Laurie Strode in the Halloween film released in 2018, 40 years after her friends were murdered by Michael Myers on Halloween night. In that original film, she survived his attacks by wielding a knitting needle, a coat hanger and a knife that he dropped.

The grownup Strode lives an isolated life in a fortress in the woods, always on the lookout for the looming threat of Myers' return. Earlier in her adult life, viewers learn, her paranoia had rendered her an unfit mother in the eyes of authorities and her daughter was taken away.

In the article, Podraza, a PhD student in English, examines the representation of Strode's trauma in the 2018 Halloween sequel to the 1978 original, and how the depiction of her struggle after survival - how she has been vilified and dismissed, but ultimately proven right - might offer trauma survivors the chance to see a bit of themselves on the big screen.

"The way this film specifically deals with cycles of trauma and their connection to the experiences of survivors was really important to me because I think it is indicative of how we talk about trauma and survivors of trauma even today, and ways that people are spoken about negatively - their trauma is not acknowledged or they're not given an opportunity for healing," Podraza said.

"We can use the final girl trope now to reimagine spaces for healing or futures for people with trauma. A survivor's future will always include memories of that trauma, and it's important to acknowledge that trauma exists and continues to affect the reality of people who experience it.

"They deserve happy, healthy futures, too. People don't have to only be defined by the negative parts of this experience."

Podraza's scholarship centers on comics and animated film, but as a life-long fan of horror movies, she saw an opportunity to tie her interest in women-centered narratives and narratives of trauma to a favorite genre after the 2018 sequel release, which coincided with the #metoo movement.

When the sequel came out, Curtis herself called attention to the intersection of fiction and reality, telling Variety that she thought women battling their own trauma would be able to relate to Strode's desperate attempts to convince skeptics that Michael Myers was still a threat: "It feels like a confluence of that frustration and that rise of empowerment has come together in this movie in a beautiful way." Those promotional interviews resonated with Podraza.

"The scholarship hasn't looked beyond the final girl's survival and triumph. The final girl context has always been that she survived and that's enough. Or she killed the monster and that's enough. That's fine, but that's not how people's experiences work," she said. "Trauma is about the effects after the event is over."

The final girl trope was defined by scholar Carol Clover in the 1992 book Men, Women, and Chain Saws: Gender in the Modern Horror Film. The Laurie Strode character was central to Clover's definition of the trope, and while she emphasized that trauma helped characterize the final girl, the analysis stopped short of examining its effects.

Podraza cites scholarship in her article noting that survival of trauma itself is a crisis, that moving forward with life after a traumatizing event is also traumatic. The Laurie Strode character shows how this might look: Her obsession with protecting herself and others is tethered to her survival, and her outlook on life - a life saved by her own hand - remains grim because she's convinced she is subject to a continuing threat.

An analysis like this isn't intended to detract from the thrill of watching horror and slasher films, said Podraza, who advises her students to consume media for enjoyment first, and then re-watch or re-read the material with an eye toward asking critical questions.

"It's perfectly fine to just enjoy media, but it's always important to be aware of how media is framing experiences, especially experiences of people who are marginalized in any way. Survivors of trauma often are marginalized," she said. "The danger is to absorb media and never ask questions about it - that means you're not aware of how it's structuring your own behaviors and habits."

The franchise is slated to continue with the release of Halloween Kills in October and, in 2022, Halloween Ends. Based on the closing scene of the 2018 sequel, of Strode's granddaughter holding a bloody knife that she used to defend herself, Podraza sees potential for a depiction of intergenerational trauma.

"The structure of the franchise implies the cycle will just continue," she said, "and I am interested in how these concepts will perpetuate."

DALLAS - May 28, 2021 - A study of gene activity in the brain's hippocampus, led by UT Southwestern researchers, has identified marked differences between the region's anterior and posterior portions. The findings, published today in Neuron, could shed light on a variety of brain disorders that involve the hippocampus and may eventually help lead to new, targeted treatments.

"These new data reveal molecular-level differences that allow us to view the anterior and posterior hippocampus in a whole new way," says study leader Genevieve Konopka, Ph.D., associate professor of neuroscience at UTSW.

She and study co-leader Bradley C. Lega, M.D., associate professor of neurological surgery, neurology, and psychiatry, explain that the human hippocampus is typically considered a uniform structure with key roles in memory, spatial navigation, and regulation of emotions. However, some research has suggested that the two ends of the hippocampus - the anterior, which points downward toward the face, and the posterior, which points upward toward the back of the head - take on different jobs.

Scientists have speculated that the anterior hippocampus might be more important for emotion and mood, while the posterior hippocampus might be more important for cognition. However, says Konopka, a Jon Heighten Scholar in Autism Research, researchers had yet to explore whether differences in gene activity exist between these two halves.

For the study, Konopka and Lega, both members of the Peter O'Donnell Jr. Brain Institute, and their colleagues isolated samples of both the anterior and posterior hippocampus from five patients who had the structure removed to treat epilepsy. Seizures often originate from the hippocampus, explains Lega, who performed the surgeries. Although brain abnormalities trigger these seizures, microscopic analysis suggested that the tissues used in this study were anatomically normal.

After removal, the samples underwent single nuclei RNA sequencing (snRNA-seq), which assesses gene activity in individual cells. Although snRNA-seq showed mostly the same types of neurons and support cells reside in both sections of the hippocampus, activity of specific genes in excitatory neurons - those that stimulate other neurons to fire - varied significantly between the anterior and the posterior portions of the hippocampus. When the researchers compared this set of genes to a list of genes associated with psychiatric and neurological disorders, they found significant matches. Genes associated with mood disorders, such as major depressive disorder or bipolar disorder, tended to be more active in the anterior hippocampus; conversely, genes associated with cognitive disorders, such as autism spectrum disorder, tended to be more active in the posterior hippocampus.

Lega notes that the more researchers are able to appreciate these differences, the better they'll be able to understand disorders in which the hippocampus is involved.

"The idea that the anterior and posterior hippocampus represent two distinct functional structures is not completely new, but it's been underappreciated in clinical medicine," he says. "When trying to understand disease processes, we have to keep that in mind."

In 2015, nearly half of Hawai?i's coral reefs were affected by the most severe bleaching event to date. Coral bleaching occurs when warmer-than-normal ocean temperatures prompt corals to expel the algae that normally live inside them and on which the corals rely for food.

Bleaching events are dismaying, but corals can sometimes recover, while others resist bleaching altogether. In a new study in the journal Proceedings of the National Academy of Sciences, researchers led by Katie Barott of the University of Pennsylvania found that these battle-tested, resilient corals could thrive, even when transplanted to a different environment and subjected to additional heat stress. The findings offer hope that hardy corals could serve as a founding population to restore reefs in the future.

"The big thing that we were really interested in here was trying to experimentally test whether you an take a coral that seems to be resistant to climate chage and use that as the seed stock to propagate and put out on a different reef that might be degraded," Barott says. "The cool thing was we didn't see any differences in their bleaching response after this transplant."

Mass coral bleaching events are getting increasingly frequent, raising worries that corals will become victims of climate change in the near future. Yet Barott and colleagues have been studying the corals that resist bleaching, with an eye toward buying corals more time to hang on in the face of warming and acidifying ocean waters.

One strategy they and others have envisioned, and which has been trialed in areas such as the Great Barrier Reef, is coral transplantation. Researchers could replenish reefs damaged by climate change--or other anthropogenic insults, such as sedimentation or a ship grounding--with corals that had proved sturdy and able to survive in the face of tough conditions.

For this to work, however, would require the coral "survivors" to continue to display their resilient characteristics after being moved to a new environment.

"If you take a coral that is resistant to bleaching in its native habitat, it could be that the stress of moving to a new place might make them lose that ability," Barott says.

Just as a fern that grew well in the shade might wilt if moved to a sunny plot, the conditions of a new environment, including water flow rate, food access, light, and nutrient availability, could could affect the resilience of transplanted corals.

Barott and colleagues went after this question with an experiment in two reefs in Hawai?i's Ka?ne?ohe Bay on the island of O?ahu: one closer to shore with more stagnant waters and another farther from shore with higher flow. In each area, the researchers identified coral colonies that had resisted bleaching during the 2015 bleaching event and collected samples from them the following year. Corals are clonal organisms, and so a chunk taken from a colony can regrow and will have the same genetics as the "mother" coral. For each colony, they kept some samples on their native reef and transplanted others to the second reef.

After the corals had spent six months at their new location, the biologists also put coral samples from each site in tanks in the lab and simulated another bleaching event by raising the water temperature over a period of several days.

Carefully tracking the corals' health and the conditions of the surrounding environment, the team measured photosynthesis rates, metabolism, and calcification rates, as well as the health of the symbiotic algae. They found that bleaching-resistant corals stayed that way, even in a new environment.

"What was really novel is that we had this highly replicated experiment," Barott says, "and we saw no change in the coral's bleaching response."

The researchers also looked at how well the corals reproduced the summer that followed their collection. A coral's native site conditions had an impact on their future reproductive fitness, they discovered.

"The corals from the 'happy' site--the outer lagoon that had higher growth rates prior to the bleaching event--generally seemed a little happier and their fitness was higher," Barott says. "That tells us that, if you're going to have a coral nursery, you should pick a site with good conditions because there seems to be some carryover benefit of spending time at a nicer site even after the corals are outplanted to a less 'happy' site."

The "happy" site, the lagoon farther from shore, had higher flow rates than the other reef, which is closer to shore, less salty, and more stagnant. "Higher flow rates are really important for helping corals get rid of waste and get food," Barott says.

Barott, who started the work as a postdoc at the Hawai?i Institute of Marine Biology, is continuing to pursue research on coral resiliency in her lab at Penn, including an investigation of the effects of heat stress and bleaching on reproductive success and the function of coral sperm.

While the results of the transplantation study are promising, she says that it would only be a temporary solution to the threat of climate change.

"I think techniques like this can buy us a little bit of time, but there isn't a substitute for capping carbon emissions," she says. "We need global action on climate change because even bleaching-resistant corals aren't going to survive forever if ocean warming keeps increasing as fast as it is today."

Professor YAO Huajian's research group from the School of Earth and Space Sciences of the University of Science and Technology of China (USTC), in cooperation with Dr. Piero Poli from Grenoble-Alpes University of France, combined the unique resolution reflected body waves (P410P and P660P) retrieved from ambient noise interferometry with mineral physics modeling, to shed new light on transition zone physics. Relevant work was published in Nature Communications.

The subduction of oceanic slabs is an important process of the earth's internal material circulation. Studying the recycling of oceanic crust in the deep mantle can provide crucial clues for understanding mantle dynamics and circulation of deep materials. However, this is barely constrained by reliable seismic evidence.

The mantle transition zone (MTZ) is bounded by global seismic discontinuities near 410-km and 660-km discontinuities. The structure and properties of this zone have a crucial influence on the process of mantle convection. Because that the basaltic oceanic crust with a lower density than the normal mantle has negative buoyancy near the 660-km discontinuity, so that it may be gravitationally trapped in this region. However, the narrow depth ranges of the negative buoyancy and the lower temperature and viscosity of the subducted oceanic slabs bring many uncertainties to this speculation. It's still controversial whether the subducted oceanic crust can be segregated from the oceanic lithospheric mantle and stay at that transition zone.

The traditional methods on the structure of the transition zone mainly based on the traveltime and amplitude information of natural earthquake body wave phases that were often restricted by the temporal and spatial distribution of natural earthquakes.

In this study, researchers used the continuous waveform data from more than 200 stations in North China to calculate the background noise cross-correlation function. The result obtains clear reflected seismic phases between 410-km and 660-km. There are significant P660P waveform anomalies on the front edge of the stagnant Pacific Plate, which was well explained by a simple mineral model that: the segregated basaltic oceanic crust is accumulated at the bottom transition zone at the front edge of the subduction slab.

This study revealed that the subducted oceanic plate has long been trapped at the bottom of the mantle transition zone, which may undergo mantle-crust segregation due to the increase in temperature and the decrease of the viscosity. The segregated oceanic crust may stay at the bottom of the mantle transition zone for the negative buoyancy and this can well explain the observed seismic scattering and week P660P phase. The oceanic plates that penetrate directly through the transition zone are difficult to segregate due to the rapid velocity and lower temperature (higher viscosity).

Furthermore, these subducted slabs are heated at the core-mantle boundary, where crust-mantle segregation is more likely to occur. The separated oceanic crust components will be accumulated above the core-mantle boundary or carried to the shallow part by the mantle plume.

Therefore, the evolution and cycle process of oceanic crust components are closely related to the subduction pattern of oceanic slabs. The material-filtering effect of the 660-km interface may play a crucial role in the chemical evolution of our planet.

UNIVERSITY PARK, Pa. -- A Penn State scientist studying crystal structures has developed a new mathematical formula that may solve a decades-old problem in understanding spacetime, the fabric of the universe proposed in Einstein's theories of relativity.

"Relativity tells us space and time can mix to form a single entity called spacetime, which is four-dimensional: three space-axes and one time-axis," said Venkatraman Gopalan, professor of materials science and engineering and physics at Penn State. "However, something about the time-axis sticks out like sore thumb."

For calculations to work within relativity, scientists must insert a negative sign on time values that they do not have to place on space values. Physicists have learned to work with the negative values, but it means that spacetime cannot be dealt with using traditional Euclidean geometry and instead must be viewed with the more complex hyperbolic geometry.

Gopalan developed a two-step mathematical approach that allows the differences between space and time to be blurred, removing the negative sign problem, serving as a bridge between the two geometries.

"For more than 100 years, there has been an effort to put space and time on the same footing," Gopalan said. "But that has really not happened because of this minus sign. This research removes that problem at least in special relativity. Space and time are truly on the same footing in this work." The paper, published today (May 27) in the journal Acta Crystallographica A, is accompanied by a commentary in which two physicists write that Gopalan's approach may hold the key to unifying quantum mechanics and gravity, two foundational fields of physics that are yet to be fully unified.

"Gopalan's idea of general relativistic spacetime crystals and how to obtain them is both powerful and broad," said Martin Bojowald, professor of physics at Penn State. "This research, in part, presents a new approach to a problem in physics that has remained unresolved for decades."

In addition to providing a new approach to relate spacetime to traditional geometry, the research has implications for developing new structures with exotic properties, known as spacetime crystals.

Crystals contain repeating arrangement of atoms, and in recent years scientists have explored the concept of time crystals, in which the state of a material changes and repeats in time as well, like a dance. However, time is disconnected from space in those formulations. The method developed by Gopalan would allow for a new class of spacetime crystals to be explored, where space and time can mix.

"These possibilities could usher in an entirely new class of metamaterials with exotic properties otherwise not available in nature, besides understanding the fundamental attributes of a number of dynamical systems," said Avadh Saxena, a physicist at Los Alamos National Laboratory.

Gopalan's method involves blending two separate observations of the same event. Blending occurs when two observers exchange time coordinates but keep their own space coordinates. With an additional mathematical step called renormalization, this leads to "renormalized blended spacetime."

"Let's say I am on the ground and you are flying on the space station, and we both observe an event like a comet fly by," Gopalan said. "You make your measurement of when and where you saw it, and I make mine of the same event, and then we compare notes. I then adopt your time measurement as my own, but I retain my original space measurement of the comet. You in turn adopt my time measurement as your own, but retain your own space measurement of the comet. From a mathematical point of view, if we do this blending of our measurements, the annoying minus sign goes away."

A groundbreaking clinical trial shows we can reduce biological age (as measured by the Horvath 2013 DNAmAge clock) by more than three years in only eight weeks with diet and lifestyle through balancing DNA methylation.

A first-of-its-kind, peer-reviewed study provides scientific evidence that lifestyle and diet changes can deliver immediate and rapid reduction of our biological age. Since aging is the primary driver of chronic disease, this reduction has the power to help us live better, longer.

The study, released on April 12, utilized a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients, resulting in a statistically significant reduction of biological age--over three years younger, compared to controls.

The study was independently conducted by the Helfgott Research Institute, with laboratory assistance from Yale University Center for Genome Analysis, and the results independently analyzed at McGill University and the National University of Natural Medicine.

The study’s lead author, Kara Fitzgerald ND IFMCP, stated that “the combined intervention program was designed to target a specific biological mechanism called DNA methylation, and in particular the DNA methylation patterns that have been identified as highly predictive of biological age. We suspect that this focus was the reason for its remarkable impact. These early results appear to be consistent with, and greatly extend, the very few existing studies that have so far examined the potential for biological age reversal. And it is unique in its use of a safe, non-pharmaceutical dietary and lifestyle program, control group, and the extent of the age reduction. We are currently enrolling participants for a larger study which we expect will corroborate these findings.”

Leading epigeneticist Moshe Szyf PhD of McGill University and co-author on the study adds, “The uniqueness of Dr Fitzgerald approach is that her trial devised a natural but mechanistic driven strategy to target the methylation system of our body. This study provides the first insight into the possibility of using natural alterations to target epigenetic processes and improve our well being and perhaps even longevity and lifespan.”

DNA methylation patterns have become a leading means by which scientists evaluate and track biological aging, a term used to describe the accumulation of damage and loss of function to our cells, tissues and organs. This damage is what drives diseases of aging. “What is extremely exciting,” commented Dr. Fitzgerald, “is that food and lifestyle practices, including specific nutrients and food compounds known to selectively alter DNA methylation, are able to have such an impact on those DNA methylation patterns we know predict aging and age-related disease. I believe that this, together with new possibilities for us all to measure and track our DNA methylation age, will provide significant new opportunities for both scientists and consumers.”

Varying immune response to vaccinations could be countered with microbiota-targeted interventions helping infants, older people and others to take full advantage of the benefits of effective vaccines, Australian and US experts say.

A comprehensive review in Nature Reviews Immunology concludes that evidence is mounting in clinical trials and other studies that the composition and function of individuals' gut microbiota are "crucial factors" in affecting immune responses to vaccinations.

"Never before has the need been greater for robust and long-lasting immunity from our vaccination programs, particularly in low and middle-income countries, and for populations at increased risk of infectious diseases such as infants or the elderly," says lead researcher Flinders University Professor David Lynn, an EMBL Australia Group Leader based at the South Australian Health and Medical Research Institute (SAHMRI).

Vaccine protection is induced by B cells that produce antigen-specific antibodies but T cells also help mediate the protection induced by some vaccines.

"Our study found increasing evidence that gut microbiota - which is highly variable between individuals, over the course of life and between various populations around the world - as a crucial factor modulating B and T cell immune responses to vaccinations," says co-author, Flinders University PhD candidate Saoirse Benson.

"A better understanding of how the microbiota regulates these vaccine responses may also inform the use of more tailored population-specific adjuvants to enhance responses to vaccinations," she says.

"There is more we can do to optimise existing vaccine effectiveness by understanding more about gut microbiota and interventions such as prebiotics and probiotics."

The research group uses germ-free mice, or mice with no microbiome, to assess which bacteria are best at supporting immune responses to vaccination.

Professor Lynn's research group is also currently analysing the results of a clinical study of how the impact of antibiotics on the gut microbiome of infants may affect immune responses to routine childhood vaccinations.

In separate studies, the lab is also assessing COVID-19 vaccine immune responses and coordinating the Australian BRACE trial funded by the Gates Foundation to test whether the BCG vaccine can protect healthcare workers who contract COVID-19 from developing severe symptoms.

Research across a wide range of languages shows that children's home literacy environment can often predict their language and literacy skills. However few studies, especially for English speaking children, examine how children's development affects what parents do and not just how parents affect their children's development. A new longitudinal study examined such bidirectional relationships between home literacy environment and children's progress in learning to read between grades 1 and 3. Results show that parents adjust their reading activities with their children over time, taking into account the level of difficulty the children are having in learning to read. These findings raise the important possibility that teachers could give more specific guidance to parents to help shape the home literacy environment according to children's progress in learning to read.

Results showed that access to literacy resources was a consistent predictor of emergent literacy over time. However, in addition, while parent-child reading comprehension activities and parent ratings of the child's interest in reading at the start of grade 1 predicted children's reading accuracy and comprehension in second grade, there was a switch at that point in the relationship of parent activities and children's development. From then on, parents started to engage in more frequent reading comprehension activities with their children when they realized their children were experiencing reading difficulties. Across ages, the findings point to the importance of reading comprehension activities as more important than the overall frequency of reading activities with parents.

The findings were published in a Child Development article, written by researchers at the University of Alberta, The Chinese University of Hong Kong, and Macquarie University.

"Our study showed that there is a bidirectional relationship between early access to literary resources at home, child interest and child's reading skills in grade 2," said George Georgiou, professor in the department of educational psychology at the University of Alberta. "These findings are important because they show that it is not only home literacy environment that predicts future reading, but that earlier reading also predicts future home literacy environment."

The sample included 172 children recruited from six public elementary schools in Edmonton, Canada. The children were tested at the beginning of grade 1 and at the end of grades 2 and 3 to assess their reading accuracy and comprehension and asked to respond to a child- friendly measure of interest in reading. Measures included the following:

Reading interest: feelings about reading for fun at home, getting a book, spending free time reading, starting a new book, reading through the weekend, reading instead of playing, going to a library or bookstore, and reading different kind of books.

Phonological awareness: ability to repeat recording of a native English speaker and then remove a designated sound from it and say what was remaining.

Vocabulary: capacity for defining words increasing in difficulty.

Reading accuracy: ability to read out loud and pronounce pseudowords of increasing difficulty.

Reading comprehension: skill level for reading short passages and providing an appropriate word to fill in the blank and sentence matching indicating understanding of meaning.

During grade 1, and at grades 2 and 3, parents completed questionnaires assessing different aspects of the home literacy environment including:

Direct teaching: frequency of how often they or someone else at home taught their child to read or spell words.

Shared book reading: regularity of reading a story to their child on a weeknight or weekend.

Access to literacy resources: number of printed children's books at home.

Reading comprehensive activities: frequency of asking their child to talk about the content, characters/events in a story they read or summarize the story.

Reading interest: rating of how often their child was reading alone for enjoyment and how much they enjoyed being read to.

Family socioeconomic status: self-report of parents' highest achieved education and their occupations.

The study showed that access to literacy resources was the main predictor of emergent literacy skills over time. The findings also showed that onward from grade 1, frequency of shared book reading was not significantly related to children's reading skills, which may indicate that quality of parent-child interactions is more important for children's language and literacy skills than the frequency of this activity after a certain point. Finally, in line with previous research, the findings also suggest that parents should engage frequently in reading comprehension activities with their children.

"The findings indicate that reading comprehension activities seem to play a key role in predicting reading skills and should be considered an important component in supporting literacy in the home," said Georgiou and his collaborators Tomohiro Inoue, assistant professor in the department of psychology at the Chinese University of Hong Kong and Rauno Parrila, professor in the school of education at Macquarie University. "Results from the study also allowed us to observe whether parents adjusted their home literacy practices depending on their children's reading performance. After a certain point in development, the findings indicate that parents are more likely to engage in reading comprehension activities when they realize their child is experiencing difficulties."

The authors note that the study is correlational, and relations do not imply causation. The authors also acknowledge several limitations around the measurements of the home literacy environment. Home literacy was measured by a self-reported questionnaire completed by parents which may be subject to social desirability bias (e.g., answering questions in a manner that will be viewed favorably by others.) The parent questionnaires also focused on the quantity, not quality of the parent-child interactions, and did not assess whether there were naturally occurring home literacy activities or parental involvement during homework. Finally, the authors did not directly assess how much independent reading the parents themselves were engaged in.

INDIANAPOLIS -- A pilot project using an online survey to gather data on COVID-19 symptoms received more than 87,000 responses from around the world, providing important insight into the spread of disease. Project leaders from Regenstrief Institute, Indiana University and Microsoft believe these questionnaires could be a valuable tool for population health.

The 7-question survey was launched in multiple languages during April 2020, as lockdowns were implemented to slow the spread of COVID-19. A link to the survey was placed in banner ads in Microsoft News articles. Respondents answered questions about experiencing COVID-19 symptoms, testing and their recent travel. The survey was voluntary and anonymous.

The survey captured 87,322 respondents during a three-week period. Responses included people from every U.S. state and nearly every county in each state. 85.2 percent of the respondents were from the U.S. and Japan, and more than half of those were 50 years or older.

"We found this survey method to be feasible for collecting large-scale data from people in the community, enhancing disease surveillance," said study author Brian Dixon, PhD, MPA, director of public health informatics at Regenstrief Institute and IU Richard M. Fairbanks School of Public Health at IUPUI. "The population in this survey skewed older and reflects individuals who participate in traditional opinion surveys. Volunteers come across our call for help while, simply, reading the news. Other social media sites trend younger and draw from individuals constantly bombarded with quizzes and marketing surveys. Furthermore, the news platform we used was able to reach the population who is at higher risk of complications from COVID-19, which is important to monitor and target in public health efforts during this pandemic."

The data gathered is unique because it comes from community residents rather than people who were hospitalized with the disease. The survey revealed several interesting insights about patterns of symptoms.

* Those who reported loss of taste or smell and fever, symptoms associated with active SARS-CoV-2 infection, were more likely to have been tested for COVID-19.
* Individuals reporting symptoms were more likely to report travelling more than 15 miles from their home within the past two weeks.
* Those without symptoms were significantly less likely to report being tested. However, testing infrastructure in the U.S. was limited at the time of the survey.
* The number of people reporting symptoms was correlated with the testing rates in U.S. states, indicating that symptom monitoring could be a proxy for testing in places where testing might be limited.

"This approach offers access to a wide audience, many of whom might not be captured in other data gathering methods," said study author Mary L. Gray, PhD, senior principal researcher at Microsoft Research and faculty at Indiana University Luddy School of Informatics, Computing, and Engineering. "This work sheds light on the potential uses of this method for the current pandemic and other circumstances where data gathering at scale is needed quickly."

"Based on our results, online news tools can be a useful strategy for reaching broad and diverse populations during emerging outbreaks. It is a quick and easy way to gather a significant amount of data and appears to accurately capture what is happening in the community at large," said study author Shaun Grannis, M.D., M.S., Regenstrief vice president for data and analytics and IU School of Medicine professor of family medicine. "Combined with other methods, online news tools can help public health organizations quickly assess trends in emerging infections before individuals seek treatment, allowing a faster public health response."

The research team launched a second online survey in December 2020 to expand efforts to track symptoms, understand population behavior, and gather insights on vaccine attitudes.